CCTS Research Projects

ABOVE Trial – Advancing Brain Outcomes in pediatric critically ill patients sedated with Volatile anEsthestic agents (ABOVE): A pilot multicentre randomized controlled trial

Principal investigator

• Dr. Angela Jerath, Sunnybrook Health Sciences Centre
• Dr. Rishi Ganesan, The Children’s Hospital – London Health Sciences Centre
• Dr. Nicole McKinnon, The Hospital for Sick Children (SickKids)
• Dr. Marat Slessarev, London Health Sciences Centre

Recruitment Status

Recruiting

Summary

The ABOVE Trial is a pilot, multicenter, vanguard randomized controlled trial (RCT) to assess the feasibility of accruing patients, delivering inhaled sedatives, and ascertaining outcomes in preparation for a definitive trial to evaluate if inhaled sedatives (intervention) compared to intravenous (IV) agents (comparator) improve delirium (outcome) in mechanically ventilated critically ill children (population).

Sample Size: This pilot trial aims to recruit 60 children who require mechanical ventilation in the pediatric intensive/critical care unit (PICU/PCCU).

Intervention: Participants will be randomized to either the control arm (IV sedation) or the intervention arm (inhaled sedation).

Outcomes: The primary outcome is patient accrual and identifying barriers to recruitment. Secondary outcomes will assess protocol adherence, attrition rate, safety/adverse event rate, and healthcare team satisfaction.

ClinicalTrials.gov (NCT#)

NCT05867472

Trial Email

ABOVETrial@sunnybrook.ca

Trial Locations

• The Children’s Hospital – London Health Sciences Centre, London, Ontario
• The Hospital for Sick Children (SickKids), Toronto, Ontario

ATTAACH – Pilot Randomized Controlled Trial of Anticoagulation Therapy Timing in Atrial Fibrillation after Acute and Chronic Subdural Hematoma

Principal Investigator

Dr. Farhad Pirouzmand, Sunnybrook Health Sciences Centre

Recruitment Status

Terminated (Halted Prematurely)

Summary

ATTAACH is a pilot, open label, multi-centre, pragmatic randomized controlled trial that is planned to simulate all aspects of a larger definitive trial comparing early versus delayed resumption of anticoagulation for stroke prophylaxis secondary to atrial fibrillation after subdural hematoma (SDH) in appropriately selected patients with atrial fibrillation (AF).

This pilot will help determine the ability to meet pre-specified criteria in identification, recruitment, and participant allocation; allow for refinement of eligibility criteria for optimal recruitment; confirm safety of intervention and; examine the ability to retain participants for the duration of the trial and collect follow-up data. Preliminary efficacy data will inform sample size calculations and estimation of resources required for the envisioned larger definitive trial. If the pilot trial is found to be feasible and there are no major changes to the protocol, then the data will contribute to the final analysis of the definitive trial (i.e., vanguard design).

The study aims to enroll 120 participants over an 18 month period at 7 centres across Canada.

ClinicalTrials.gov (NCT#)

NCT05472766

Trial Email

ATTAACH_Trial@sunnybrook.ca

Trial Locations

Ontario

CATCO – A Multi-centre, Adaptive, Randomized, Open-label, Controlled Clinical Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Patients

Principal Investigator

• Dr. Rob Fowler, Sunnybrook Health Sciences Centre
• Dr. Srinivas Murthy, University of British Columbia

Recruitment Status

Recruiting completed

Summary

CATCO is a Canadian, Phase III, multi-centre, adaptive, open-label clinical trial, conducted to investigate the safety and efficacy of various therapeutics as a treatment for COVID-19 in hospitalized patients against the current standard of care. CATCO is conducted in collaboration with countries around the world through the World Health Organizations’ (WHO) SOLIDARITY Trial PLUS. Since COVID-19 is a public health emergency that is evolving rapidly, an accurate sample size is impossible to calculate. Interim results will be reviewed at regular intervals. Given the adaptive nature of the trial, the study interventions change frequently based on interim analysis. Current information on the active study interventions/drugs can be found at ClinicalTrials.gov. The primary objective of the trial is to evaluate the clinical effectiveness of the study drugs, relative to the standard of care arm, in patients hospitalized with COVID-19, through study drug specific outcomes.

ClinicalTrials.gov (NCT#)

NCT04330690

Trial Email

CATCO@sunnybrook.ca

Trial Locations

Social Media Links

1. Follow CATCO on X @CATCOTrial
2. Sunnybrook COVID-19 Research Webpage
3. Canadian Critical Care Trials Group (CCCTG) website

Publications

1. Remdesivir for the treatment of patients in hospital with COVID-19 in Canada: a randomized controlled trail
2. Remdesivir in Patients with Severe Kidney Dysfunction
3. Cost-effectiveness of remdesivir plus usual care versus usual care alone for hospitalized patients with COVID-19
4. WHO SOLIDARITY Publications, which included CATCO Data
   1. Repurposed Antiviral Drugs for COVID-19 – Interim WHO SOLIDARITY Trial Results
   2. Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses

HONOUR – High-Flow Nasal Oxygen with or without Helmet Non-invasive Ventilation for Oxygenation Support in Acute Respiratory Failure (HONOUR) Pilot RCT

Principal Investigator

• Dr. Damon Scales, Sunnybrook Health Sciences Centre
• Dr. Niall Ferguson, University Health Network-Toronto General Hospital

Recruitment Status

Recruiting

Summary

HONOUR is a pilot, open-label randomized controlled trial to assess the feasibility of conducting a large multicenter randomized controlled trial. It will directly compare helmet non-invasive ventilation (NIV) combined with high flow nasal oxygen (HFNO) versus HFNO alone in patients with AHRF. The projected sample size is 200 participants across 10-15 Canadian sites, and the primary outcomes are:

1. To determine whether it is feasible to recruit 1 patient per month per participating centre, and to estimate the potential recruitment rate for the full trial.
2. To assess the proportion of eligible patients who are not randomized (and their reasons).
3. To determine the rate of adherence to the assigned oxygenation strategy (and crossover rate).
4. To estimate the adherence to pre-specified intubation criteria.
5. To estimate the median time from ICU admission to randomization and initiation of the allocated treatment, and time from initiation of any supplemental oxygen to randomization.

ClinicalTrials.gov (NCT#)

NCT05078034

Trial Email

HONOUR@sunnybrook.ca

Trial Locations

Ontario

• Toronto
• Hamilton
• Kingston
• Ottawa

Alberta

• Calgary
• Edmonton

Social Media links

X: @HONOUR_Trial

SAVE-ICU – SedAting With Volatile Anesthetics Critically Ill COVID-19 Patients in ICU: Effects On Ventilatory Parameters And Survival

Principal Investigators

• Dr. Angela Jerath, Sunnybrook Health Sciences Centre
• Dr. Brian Cuthbertson, Sunnybrook Health Sciences Centre
• Dr. Marat Slessarev, London Health Sciences Centre
• Dr. Claudio Martin, London Health Sciences Centre

Recruitment Status

Recruiting

Summary

SAVE-ICU is a multi-centre, randomized clinical trial studying the effectiveness of inhaled volatile sedation versus intravenous sedation for COVID-19 patients that need to be placed on a ventilator.

The purpose of the study is to evaluate whether inhaled volatile sedation can be used effectively in ventilated COVID-19 patients, thereby easing pressure on IV sedation stocks. The study is also evaluating if patients recover faster with this form of sedation.

Sample Size: 758 participants

Interventions: Participants will be randomized to either an intravenous or inhaled volatile-based sedation arm.

Primary Outcomes:

1. Hospital Mortality with 10% difference between groups (752 participants),
2. Ventilator-free-days at day 30 after enrollment (200 patients)
3. Quality of life using EQ-5D at 90 days and 365 days after enrollment (144 participants)
4. ICU-free-days at day 30 after enrollment (128 participants)

ClinicalTrials.gov (NCT#)

NCT04415060

Trial Email

SAVE-ICU@sunnybrook.ca

Trial Locations

• Sunnybrook Health Sciences Centre (Toronto, Ontario, Canada)
• London Health Sciences Centre – Victoria Hospital (London, Ontario, Canada)
• London Health Sciences Centre – University Hospital (London, Ontario, Canada)
• UHN – Toronto General Hospital (Toronto, Ontario, Canada)
• UHN – Toronto Western Hospital (Toronto, Ontario, Canada)
• The Ottawa Hospital – Civic Campus (Ottawa, Ontario, Canada)
• The Ottawa Hospital – General Campus (Ottawa, Ontario, Canada)
• University of Alberta Hospital (Edmonton, Alberta, Canada)
• Grey Nuns Community Hospital (Edmonton, Alberta, Canada)
• Centre Hospitalier de l’Université de Montréal (CHUM) (Montréal, Québec, Canada)
• Centre Intégré Universitaire de Santé et Services Sociaux de l’Estrie – Centre Hospitalier Universitaire de Sherbrooke (CHUS) (Sherbrooke, Québec, Canada)
• Centre Intégré et Universitaire de Santé et Services Sociaux du Nord de l’île de Montréal (CIUSSE-NIM-HSCM) (Montréal, Québec, Canada)
• Institut Universitaire de Cardiologie et Pneumologie de Québec (IUCPQ) (Laval, Québec, Canada)
• McGill University Health Centre – Royal Victoria Hospital (Montréal, Québec, Canada)
• McGill University Health Centre – Montreal General Hospital (Montréal, Québec, Canada)
• Massachusetts General Hospital (Boston, Massachusetts, United States)

Social Media Links

www.saveicu.com

Follow SAVE-ICU on X @SaveIcu

Publications

1. Gorsky K, Cuninghame S, Chen J, Jayaraj K, Withington D, Francoeur C, Slessarev M, Jerath A. Use of inhalational anaesthetic agents in paediatric and adult patients for status asthmaticus, status epilepticus and difficult sedation scenarios: a protocol for a systematic review. BMJ Open. 2021 Nov 10; 11(11):e051745. doi: 10.1136/bmjopen-2021-051745. PMID: 34758996; PMCID: PMC8587357. https://bmjopen.bmj.com/content/11/11/e051745.long
2. Cuninghame S, Gorsky K, Francoeur C, Withington D, Burry L, Jerath A,Slessarev M. Effect of sedation with inhaled anaesthetics on cognitive and psychiatric outcomes in critically ill adults: a systematic review protocol. BMJ Open. 2022 Feb 7; 12(2):e052893. doi: 10.1136/bmjopen-2021-052893. PMID:35131825; PMCID: PMC8822506 https://bmjopen.bmj.com/content/12/2/e052893.long

SuDDICU – A randomized controlled trial of the effectiveness and cost-effectiveness and a contemporaneous study of the ecological impact of Selective Decontamination of the Digestive tract in critically ill patients treated in Intensive Care Units.

Principal Investigator

Dr. Brian Cuthbertson, Sunnybrook Health Sciences Centre

Recruitment Status

Recruiting completed

Summary

Critically ill patients are particularly at risk of hospital acquired infections and are susceptible to higher mortality rate in addition to higher healthcare expenses. Selective decontamination of the digestive tract (SDD) is an infection-control strategy designed to reduce mortality by preventing sepsis. Suddicu is an international, investigator-initiated research collaboration with sites in Canada, Australia, and the U.K.

It is a randomized trial comparing the effect of using SDD plus standard care, to standard care alone on hospital mortality in patients receiving mechanical ventilation in the intensive care unit (ICU).

Intervention: This is an international, multicentre, crossover, cluster randomized controlled trial (x-cRCT) of eligible patients in participating ICUs using two 12-month interventional trial periods separated by a 3-month inter-period gap.

1. Topical application of antibiotic paste to mouth and throat
2. Administration of antibiotic suspension in stomach
3. A short four-day course of an intravenous antibiotic. Patients already receiving an alternative IV antibiotic as clinically indicated will not receive an additional intravenous antibiotic, but will continue the prescribed antibiotic for the usual duration of therapy.

The primary outcome is All-cause hospital mortality. This trial will answer if SDD regimen drives unknown fear of antibiotic resistance which is a threat to public health or will it prove to have a global impact by preventing infections, saving lives and reducing healthcare costs.

The trial has enroll 5000+ participants in Canada as of September 2022 and a total of 14000 patients world-wide.

ClinicalTrials.gov (NCT#)

NCT02389036

Trial Email

suDDICU@sunnybrook.ca

Trial Locations

• Ontario, Canada (7): Toronto (2), Hamilton, Niagara, Kingston, London (2)
• UK (3)
• Australia (19)

Social Media Links

• Follow SuDDICU on X @suddicu
• Study page (Sunnybrook website)
• Study page (Canadian Critical Care Trials Group)

LiFT – Lithium for Fracture Treatment: a double blind randomized controlled trial

Principal Investigator

Dr. Diane Nam, Sunnybrook Health Sciences Centre

Recruitment Status

Recruiting

Summary

The LiFT study is a participant, surgeon and observer blinded multi-centre randomized, controlled, superiority trial with 2 parallel groups. A minimization procedure will stratify participants based on site, the fractured long bone and smoking.

This study will use 300mg of Li (Lithium Carbonate) or a lactose placebo. Drug will be administered orally once daily (evening) for a total of 2 weeks starting on day 14 post fracture.

The primary endpoint is radiographic healing assessed at 8 weeks post fracture (for non-surgical patients) or post-op (for surgical patients). 160 participants will be enrolled across 5 sites in Canada.

ClinicalTrials.gov (NCT#)

NCT02999022

Trial Email

lift@sunnybrook.ca

Trial Locations

Ontario – Toronto, Ottawa, Hamilton, Barrie

Publications

Nam D, Balasuberamaniam P, Milner K, Kunz M, Vachhani K, Kiss A, Whyne C. Lithium for Fracture Treatment (LiFT): a double-blind randomised control trial protocol. BMJ Open. 2020 Jan 7;10(1):e031545. doi: 10.1136/bmjopen-2019-031545.

MAGNAM – MAGNesium and Digoxin versus AMiodarone for new onset Atrial Fibrillation in the ICU

Principal Investigator

Dr. Brian Cuthbertson, Sunnybrook Health Sciences Centre

Recruitment Status

Recruiting

Summary

Atrial fibrillation (AF) is the most common arrhythmia in the intensive care unit (ICUs), and new-onset AF in the general critical care population is associated with several downstream complications, including hemodynamic instability, thrombotic events, increased length of stay, longer duration of mechanical ventilation, and greater in-hospital mortality.

MAGNAM is a multi-centre, open-label, phase III, randomized controlled clinical trial comparing whether high dose magnesium sulphate with the addition of Digoxin as first line treatment vs AMiodarone for new onset Atrial Fibrillation in the ICU will improve the success rate in conversion to sinus rhythm and rate control, as well as speed of resolution of critical illness in new onset rapid atrial fibrillation in general ICU.

200 participants will be enrolled from 5 sites in Toronto.

ClinicalTrials.gov (NCT#)

NCT05287191

Trial Email

MAGNAM@sunnybrook.ca

Trial Locations

Toronto, Ontario

Bendamustine, Rituximab and Acalabrutinib in Waldenstrom’s Macroglobulinemia (BRAWM) – A Multi-Center, Open-Label, Single-Arm Phase II Trial of Bendamustine, Rituximab and the Next Generation BTK Inhibitor Acalabrutinib in Previously Untreated Waldenstrom’s Macroglobulinemia

Principal Investigator

Dr. Neil L. Berinstein, Sunnybrook Health Sciences Centre

Recruitment Status

Recruiting

Summary

BRAWM is a Canadian multi-centre, open label, phase II study looking at the addition of a BTK inhibitor, acalabrutinib, to standard of care bendamustine-rituximab (BR) first line treatment of Waldenstron’s Macroglobulinemia (WM). Enrollment is to include 59 participants from 9-10 sites with WM who are symptomatic, or have hematological or biochemical compromise related to WM. Primary outcome is looking at the combined complete response and very good partial response rates of BR with acalabrutinib in patients with WM in the first 18 months of treatment.

ClinicalTrials.gov (NCT#)

NCT04624906

Trial Email

brawm@sunnybrook.ca

Trial Locations

CLIMB-LMD – Tucatinib, Trastuzumab and Capecitabine with brain and/or spinal radiotherapy (XRT) in patients with HER2+ metastatic breast cancer and leptomeningeal disease: A multi-centre phase II, single arm feasibility study.

Principal Investigator

Dr. Katarzyna Jerzak, Sunnybrook Health Sciences Centre

Recruitment Status

Recruiting

Summary

The CLIMB-LMD trial is A multi-center phase II, single arm, open-label feasibility study with a safety run-in of 6 subjects. A total of 30 participants will be enrolled in the trial from approximately 10 centers across Canada. The primary outcome is to assess the overall survival (OS) from the start of XRT.

Trial Email

CLIMB-LMD@sunnybrook.ca

PERIOP-06 – A Phase II Study of Perioperative QBECO Site Specific Immunomodulator (Qu Biologics®) in Patients with Metastatic Colorectal Adenocarcinoma within the Liver Undergoing Resection

Principal investigator

Dr. Paul Karanicolas: Sunnybrook Health Science Centre

Dr Rebecca Auer: The Ottawa Hospital Research Institute

Recruitment Status

Recruiting

Summary

PERIOP-06 is a multicenter, phase II, blinded, randomized, placebo-controlled trial in adult patients planned to undergo resection of colorectal liver metastases (CRLM) for complete clearance of all visible disease. The investigational product for the study is QBECO. QBECO is a site specific immunomodulator (SSI) designed to promote innate immune responses in the gastrointestinal tract and related organs, including the liver. This trial is motivated by the promising preclinical and clinical data supporting the safety and efficacy of QBECO in attenuating postoperative immunosuppression and the resulting proliferation of cancer.

The primary objective of this randomized controlled trial is to determine if QBECO administered perioperatively can improve 2-year Progression-Free Survival in adult patients undergoing resection of CRLMs for complete clearance of metastatic disease. The main secondary objectives will be to:

1. Determine the effect of QBECO on the frequency and kinetics of clearance (and recurrence) of circulating tumor DNA (ctDNA) in the postoperative period and further evaluate the use ctDNA as part of ongoing surveillance.
2. Determine the side-effect profile of perioperative QBECO
3. Determine the effect of QBECO on 5-year overall survival

Approximately 115 participants will be randomized to receive a placebo or the investigational product, QBECO. QBECO or placebo will be administered according to the following regimen: 0.1mL subcutaneous injections every two days for 11-120 days preoperatively, and 41 days postoperatively. Participants will be followed for 5 years after surgery.

ClinicalTrials.gov (NCT#)

NCT05677113

Trial email

PERIOP-06@sunnybrook.ca

Trial Locations

Toronto; Ottawa; Kingston; Hamilton; London

SPiReL – Phase 2 Study of an Immune Therapy, DPX-Survivac (maveropepimut-S (MVP-S)) with Low Dose Cyclophosphamide administered with Pembrolizumab in Patients with persistent or recurrent/refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Principal investigators

Dr. Neil L. Berinstein, Sunnybrook Health Sciences Centre

Recruitment status

Recruitment completed

Summary

SPiReL was a Phase 2, non-randomized, open-label, uncontrolled, efficacy and safety trial in patients with relapsed/refractory DLBLC. 25 participants were enrolled.
Participants received two 0.5 mL priming injections of DPX-Survivac (MVP-S) three weeks apart and up to six 0.1mL maintenance injections, subcutaneously over the course of the study. Participants received metronomic oral cyclophosphamide (50mg BID; 7 days on / 7 days off) for study period. Pembrolizumab 200mg was administered intravenously every three weeks.
Clinical efficacy was evaluated using the Modified Cheson Criteria and measurements of changes in tumour volume from baseline CT scans.

ClinicalTrials.gov (NCT#)

NCT03349450

Trial email

SPiReL@sunnybrook.ca

Trial locations

Toronto, ON; London ON, Ottawa, ON; Calgary AB; Montreal, QC; Halifax, NS

Publications

SPiReL PD-L1 expression predicts efficacy in the phase II SPiReL trial with MVP-S, pembrolizumab, and low-dose CPA in R/R DLBCL.

G-SUMIT – Phase II Pilot RCT to assess feasibility of “supra-marginal” surgical resection of malignant glioma (G-SUMIT: Glioma Supra Marginal Incision Trial)

Principal investigator

Dr. Farhad Pirouzmand, Sunnybrook Health Sciences Centre

Dr. Alireza Mansouri, Penn State University

Recruitment status

Recruiting

Summary

G-SUMIT is a Phase II pilot randomized controlled trial that will simulate all aspects of a larger definitive trial comparing conventional versus supramarginal tumor resection at the time of the first surgical resection of high grade glioblastoma (HGG).

The primary outcomes are: Feasibility of performing a large-scale trial in patients undergoing surgery for first-time diagnosis of HGG in a surgically favorable anatomical location. Specifically:

1. To establish ability to meet pre-specified criteria in identification, recruitment, allocation and outcome documentation process during trial;
2. To confirm suitability of implementing the study in multiple experienced and well-resourced centres, and;
3. To optimize inclusion/exclusion criteria for better recruitment, retention, refinement of outcome definition and estimates of the baseline rates of the safety and effectiveness outcomes in larger trial.

72 participants will enrolled from 6-8 centres.ClinicalTrials.gov (NCT#)
NCT04737577

Trial email

gsumit@sunnybrook.ca

Trial locations

Canada – Toronto, Ontario, Kingston, Ontario, Edmonton, Alberta, Saskatoon, SK. 
USA – Hershey, PA

MOCHA – A Multi-Centre, Open-Label Phase 2 Study of TRIFLURIDINE/TIPIRACIL in Previously Treated Cholangiocarcinoma

Principal investigator

Dr. Yoo-Joung Ko, Unity Health Toronto (SMH)

Summary

This is a multi-centre, open-label, single arm phase 2 study. The primary outcome is to assess the efficacy of Trifluridine/tipiracil (FTD/TPI), in patients with advanced cholangiocarcinoma as measured by median progression-free survival (PFS).

This study will enroll a total of 47 patients over a 12-month period, according to a two stage enrollment design. Nine patients will be enrolled during the first stage and the trial will be terminated if 4 or more out of the 9 have disease progression. If the trial goes on to the second stage, a total of 47 patients (38 in second stage) will be required.

FTD/TPI at 35 mg/m2 (based on BSA) will be administered in tablet form, orally, twice daily, within one hour of morning and evening meals, on days 1-5 and days 8-12 of a 28 day cycle.

Patients will be seen prior to enrolment (within 28 days of treatment), every 4 weeks while on treatment, at the end of treatment, and 30 days post-treatment. Patients will remain on long-term follow-up and will be seen every 12 weeks (+/- 14 days) until 1 year post-treatment when they will enter into the survival follow-up period and will be contacted every 12 weeks by phone until progression or toxicity.

ClinicalTrials.gov (NCT#)

NCT04076761

Trial email

MOCHA@sunnybrook.ca

Trial locations

(Toronto, Ont, Canada)

CONCEPTT Kids International

Neurodevelopmental Outcomes among Offspring of women with Type 1 Diabetes: A Follow up Study of the CONCEPTT Randomized Control Trial

Principal investigators

Dr. Jennifer Yamamoto, University of Manitoba
Dr. Lois Donovan, University of Calgary, Richmond Road Diagnostic and Treatment Centre
Dr. Deb Dewey, University of Calgary, The Owerka Centre
Dr. Denice Feig, Mount Sinai Hospital
Dr. Helen Murphy, University of East Anglia, Norwich, UK

Recruitment status

Recruiting

Summary

CONCEPTT was a multicentre randomized controlled trial of continuous glucose monitoring (CGM) in T1D pregnancies. It is the only international cohort that has detailed glycemic measures using CGM in this population. An examination of the impact of maternal glycemia (as measured by CGM) on childhood executive function and behaviour, attention, and social responsiveness has not been performed. CONCEPTT provides a unique opportunity to evaluate the relationship between direct fetal exposure to maternal glucose and these concerning childhood outcomes.

There are 225 eligible participants at 31 sites in Canada, UK, Spain and Italy.

The primary outcome measure is childhood executive function measured by the Global Executive Composite of the Behaviour Rating Inventory of Executive Function – Second Edition (BRIEF2)

ClinicalTrials.gov (NCT#)

NCT05754567

Trial email

CONCEPTTKids@sunnybrook.ca

Trial locations

Up to 31 sites in Canada, UK, Spain and Italy

Publications

Neurocognitive and behavioural outcomes in offspring exposed to maternal pre-existing diabetes: a systematic review and meta-analysis. Link: https://doi.org/10.1007/s00125-019-4923-0

MiTy Tykes – A multi-centre follow up study of the effect of in-utero exposure to metformin in 5-11 year old offspring of mothers in the MiTy Trial

Principal investigator

Dr. Denice Feig, Mount Sinai Hospital

Recruitment status

Recruiting

Summary

MiTy Tykes is an international, multi-centre, follow up study examining the offspring born to type 2 diabetic mothers who participated in the MiTy trial where they were treated with either metformin or placebo. The trial seeks to determine whether treatment with metformin during pregnancy leads to a reduction in adiposity as measured by body mass index z-score, other measures of adiposity, and growth trajectory. It will also examine measures of insulin resistance and metabolic syndrome, and Neurodevelopment. The estimated sample size is 220 participants across sites in Canada and Australia.ClinicalTrials.gov (NCT#)

NCT05025852

Trial email

mitytykes@sunnybrook.ca

Trial locations

CANADA: Toronto, Ontario; London, Ontario; Ottawa, Ontario; Halifax, Nova Scotia; Montreal, Quebec; Quebec City, Quebec; Winnipeg, Manitoba; Edmonton, Alberta; Calgary, Alberta; Vancouver, British Columbia; AUSTRALIA: Campbelltown, New South Wales, Australia; Brisbane, Queensland, Australia.

SNACS – Single Dose of Antenatal Corticosteroids (SNACS) Randomized Controlled Trial for Pregnancies at Risk of Preterm Delivery: To Keep Babies and Children Safe

Principal investigators

Dr. Sarah McDonald, McMaster University Medical Centre
Dr. Kellie Murphy, Mount Sinai Hospital

Recruitment status

Recruiting

Summary

SNACS is an international, multicenter, randomized, blinded, non- inferiority trial conducted to evaluate the outcomes of administrating a single dose of Antenatal Corticosteroids (Betamethasone) vs the standard double dose, in pregnancies, at increased risk of preterm birth. The primary clinical hypothesis is that the administration of the single does will be non-inferior for the composite outcome compared to the administration of the double dose.

The intended sample size is 3,254.

Primary outcome: A composite outcome of:

1) perinatal mortality (fetal death post-randomization or in hospital neonatal death) or

2) substantial neonatal morbidity [>1 of:

• respiratory morbidity (requiring surfactant <48 hrs of life),
• severe intraventricular hemorrhage (with ventricular distension, post-hemorrhagic ventricular dilation, intraparenchymal haemorrhage or echodense intraparenchymal lesions i.e. Grade 3 or 4),
• severe bowel problem (necrotizing enterocolitis, Stage 2 or 3)].

ClinicalTrials.gov (NCT#)

NCT05114096

Trial email

SNACS@sunnybrook.ca

Trial locations

Canada

Social media links

• Website – https://snacstrial.com/
• X – https://mobile.twitter.com/snacstrial
• Instagram – https://www.instagram.com/snacstrial/
• Facebook – https://www.facebook.com/thesnacstrial/

CHIPS – Control of Hypertension In Pregnancy Study

Principal investigator

Dr. Laura Magee, Kings College London

Summary

Women with non-severe non-proteinuric pre-existing hypertension (one per cent of deliveries) or gestational hypertension remote from term (two-three per cent of deliveries) represent a highrisk group from both maternal and perinatal perspectives. It is still unclear how best to manage the non-severe hypertension in order to do more good than harm. The placenta does not autoregulate blood flow, so allowing blood pressure (BP) to be higher may improve uteroplacental perfusion, fetal growth, and ultimately, neonatal well-being. Based on our meta-analyses of RCTs, arguments can be made both for and against ‘less tight’ control of BP (allowing for higher BP levels). ‘Less tight’ control may decrease the risk of small for gestational age (SGA) infants, but may also increase the risk of (transient) severe maternal hypertension, antenatal hospitalisation, and proteinuria at delivery. However, there is insufficient evidence on which to base clinical decisions because of reporting bias and between-trial heterogeneity in outcome. Guidelines are founded mainly on expert opinion. The CHIPS Pilot Trial confirmed the importance and feasibility of a definitive RCT. Clinicians complied with the interventions and women were satisfied with their care. ‘Less tight’ (vs. ‘tight’) control resulted in higher dBP, and a more favourable effect on perinatal outcomes.

The purpose of the CHIPS trial was to determine whether ‘less tight’ control (target dBP of 100mmHg) vs. ‘tight’ control (target dBP of 85mmHg) of non-severe maternal hypertension will decrease fetal/neonatal risk without increasing maternal risk.

ClinicalTrials.gov (NCT#)

NCT01192412

Trial locations

111 sites in 16 countries

Primary outcomes

Pregnancy loss (miscarriage or ectopic pregnancy, pregnancy termination, stillbirth, or neonatal death) or high level neonatal care for >48 hours in the first 28 days of life or prior to primary hospital discharge, whichever is later.

987 participants were enrolled in the trial.

Publications

Magee LA, von Dadelszen P, Singer J, Lee T, Rey E, Ross S, Asztalos E, Murphy KE, Menzies J, Sanchez J, Gafni A, Helewa M, Hutton E, Koren G, Lee SK, Logan AG, Ganzevoort W, Welch R, Thornton JG, Moutquin JM; CHIPS Study Group*. Hypertension. 2016 Nov;68(5):1153-1159. Epub 2016 Sep 12. https://www.ncbi.nlm.nih.gov/pubmed

CONCEPTT – Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial

Principal investigator

Dr. Denice Feig, Mount Sinai Hospital
Dr. Helen Murphy, University of East Anglia, UK

Summary

Background: Women with type 1 diabetes continue to have adverse pregnancy outcomes, including high rates of major congenital malformations, neonatal death, as well as Macrosomia.

Study design: The study will be multi-centre, computer based randomized, open label controlled and conducted as two parallel trials with an intention-to-treat analysis. Pregnant women or women planning pregnancy will be randomized to either receive the Continuous Glucose Monitor (CGM) sensor added to standard therapy or standard therapy of Home Glucose Monitoring (HGM).

Primary outcomes: Pre-pregnancy Group: Maternal glycemic control as measured by HbA1c at 24 weeks. If the patient becomes pregnant, then HbA1c will be measured post-confirmation of a positive pregnancy test and will contribute to the primary outcome.

Sample size: 324 women (110 pre-pregnant and 214 pregnant)

ClinicalTrials.gov (NCT#)

NCT01788527

Trial email

Conceptt@sunnybrook.ca

Trial locations

31 (US, Canada, Ireland, Italy, Spain, UK)

Publications

CONCEPTT: Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial: A multi-center, multi-national, randomized controlled trial – Study protocol. BMC Pregnancy and Childbirth.
https://bmcpregnancychildbirth.biomedcentral.com/articles/10.1186/s12884-016-0961-5

Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial. The Lancet. https://doi.org/10.1016/S0140-6736(17)32400-5

Continuous glucose monitoring in pregnant women with Type 1 diabetes: benefits for mothers, using pumps or pens, and their babies. Diabetic Medicine. https://doi.org/10.1111/dme.13585

Commentary: Maternal and child health – Real-time continuous glucose monitoring improves glycaemic variability and neonatal outcomes in pregnant women with type 1 diabetes; first published as 10.1136/bmjebm-2018-110927. BMJ EBM. http://dx.doi.org/10.1136/bmjebm-2018-110927

Pumps or Multiple Daily Injections in Pregnancy Involving Type 1 Diabetes: A Prespecified Analysis of the CONCEPTT Randomized Trial. Diabetes Care. https://doi.org/10.2337/dc18-1437

f.Dietary Intakes of Women with Type 1 Diabetes Before and During Pregnancy: A pre-specified secondary subgroup analysis among CONCEPTT participants. Article ID: DME13937. Diabetic Medicine. https://doi.org/10.1111/dme.13937

Modelling potential cost savings from use of real-time continuous glucose monitoring in pregnant women with type 1 diabetes. Diabetic Medicine. https://www.ncbi.nlm.nih.gov/pubmed/31162713

RESPONSE TO COMMENT ON FEIG ET AL. Pumps or Multiple Daily Injections in Pregnancy Involving Type 1 Diabetes: A Prespecified Analysis of the CONCEPTT Randomized Trial. Diabetes Care 2018;41:2471–2479. Diabetic Medicine. https://doi.org/10.2337/dci19-0013

Maternal Glycaemic Control and Risk of Neonatal Hypoglycaemia in Type 1 Diabetes Pregnancy– A secondary analysis of the CONCEPTT Trial. Diabetic Medicine. https://doi.org/10.1111/dme.13988

Dietary Patterns of Insulin Pump and Multiple Daily Injection Users During Type 1 Diabetes Pregnancy. Diabetes Care. https://doi.org/10.2337/dc19-1908

Continuous Glucose Monitoring in Pregnancy: Importance of Analyzing Temporal Profiles to Understand Clinical Outcomes https://doi.org/10.2337/dc19-2527

Which growth standards should be used to identify large- and small-for-gestational age infants of mothers with type 1 diabetes? A pre-specified analysis of the CONCEPTT trial https://doi.org/10.21203/rs.3.rs-27918/v2

Novel biochemical markers of glycemia to predict pregnancy outcomes in women with type 1 diabetes. https://doi.org/10.2337/dc20-2360

Can placental growth factors explain birthweight variation in offspring of women with type 1 diabetes? https://doi.org/10.1007/s00125-021-05438-y

Continuous glucose monitoring Time-in-Range and HbA1c targets in pregnant women with type 1 diabetes
https://doi.org/10.1089/dia.2021.0073

The Cost Implications of Continuous Glucose Monitoring in Pregnant Women with Type 1 Diabetes in Three Canadian Provinces: A Post-Hoc Cost Analysis of the CONCEPTT Trial https://doi.org/10.9778/cmajo.20200128

Reappearance of C-Peptide During the Third Trimester of Pregnancy in Type 1 Diabetes: Pancreatic Regeneration or Fetal Hyperinsulinism?

EECV2 – Early External Cephalic Version 2 Trial

Principal investigator

Dr. Eileen Hutton, McMaster University

Summary

Between 3-4 per cent of all term pregnancies will be breech. Recent research indicates that it is safest for babies in a breech presentation to be born by CS. Although most women would prefer a vaginal birth (VB), they will choose CS when there is a medical indication. Most physicians now recommend CS for breech pregnancies. CS remains the largest contributing factor to maternal mortality and serious maternal morbidity associated with birth, and the scar resulting from CS complicates all subsequent pregnancies. Research evidence supports turning breech babies using a technique called external cephalic version (ECV) beginning at 37 weeks gestation to significantly lower the CS rate and thus reduce adverse outcomes for women. Although ECV at term is effective, the procedure is often unsuccessful.

The purpose of the EECV2 trial was to determine for women with a fetus in breech presentation, does early external cephalic version (ECV) (at 340/7-356/7 weeks) versus delayed ECV (not before 370/7 weeks) increase or decrease the likelihood of caesarean section (CS)?

EECV2 was a multicentre randomised controlled trial design, with stratification for centre and parity. Participants were randomized to early ECV at 34-35 weeks or delayed ECV at ≥37 weeks.

Primary outcome was to measure rate of caesarian section.

ClinicalTrials.gov (NCT#)

NCT00141687

Trial locations

68 centres in 21 countries.

Sample size: 1543

Publications

Hutton EK, Hannah ME, Ross SJ, Delisle MF, Carson GD, Windrim R, Ohlsson A, Willan AR, Gafni A, Sylvestre G, Natale R, Barrett Y, Pollard JK, Dunn MS, Turtle P; Early ECV2 Trial Collaborative Group. BJOG. 2011 Apr;118(5):564-77. doi: 10.1111/j.1471-0528.2010.02837.x. Epub 2011 Feb 4. https://www.ncbi.nlm.nih.gov/pubmed

EMPOWER – Enhancing Breast Milk Production with Domperidone in Mothers of Preterm Neonates

Principal investigator

Dr. Elizabeth Asztalos, Sunnybrook Health Sciences Centre

Summary

EMPOWER is a multi-centre, double-masked, randomised controlled trial designed to determine if the administration of Domperidone compared to placebo will increase breast milk production without any signs of harm over a two or four week period.

The primary research question asks: In mothers of preterm infants 231/7 to 296/7 completed weeks gestation at birth who are pumping to provide expressed breast milk for their infant(s) and are identified as having an inadequate milk supply, does the administration of Domperidone compared to placebo increase breast milk volume without any signs of harm over a 2 or 4 week period?

The primary outcome is the difference between the two groups in achieving a 50 per cent increase in breast milk volume at the end of the first two-week period (mean day 14 volume- mean day volume at entry day 0).

ClinicalTrials.gov (NCT#)

NCT01512225

Trial Locations

8

Sample size: 90

Publications

Asztalos EV, Campbell-Yeo M, da Silva OP, Ito S, Kiss A, Knoppert D; EMPOWER Study Collaborative Group. J Hum Lact. 2017 Feb;33(1):181-187. doi: 10.1177/0890334416680176. Epub 2017 Jan 20.
https://pubmed.ncbi.nlm.nih.gov/28107101/

MACS – Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study

Principal investigator

Dr. Kellie Murphy, Mount Sinai Hospital

Summary

For women at increased risk of preterm birth, the benefits of a single course of antenatal corticosteroids (ACS) are well-established. These include a reduction in neonatal respiratory distress syndrome (RDS) intraventricular haemorrhage (IVH), neonatal mortality, and the need for surfactant therapy. These benefits have been demonstrated to begin 24 hours post treatment and continue up to seven days. Extrapolating these benefits, many physicians have suggested that weekly courses be given to women who remain at increased risk of preterm birth. In some centres, the practice of giving multiple courses of ACS has become routine. The study is a multicentre, double-masked randomized controlled trial (RCT). Randomization is stratified by gestational age and participating centre.
The trial set out to determine if for women at 25 to 32 weeks gestational age, 14 or more days following a single course of antenatal corticosteroids (ACS), who remain at increased risk of preterm birth: compared to placebo, are multiple courses of ACS every 14 days, until 33 weeks, effective in reducing the risk of perinatal or neonatal mortality or significant neonatal morbidity?
The primary outcome is perinatal or neonatal mortality (until 28 days of age or hospital discharge, whichever is later), or significant neonatal morbidity (one or more of the following: respiratory distress syndrome [RDS], bronchopulmonary dysplasia, grade three or four intraventricular haemorrhage (IVH), periventricular leukomalacia or necrotizing enterocolitis).

Sample size: 1858

ClinicalTrials.gov (NCT#)

NCT00187382

Trial email

macs@sw.ca

Trial locations

80

Publications

1. Multiple courses of antenatal corticosteroids for preterm birth (MACS): a randomised controlled trial. Murphy KE, Hannah ME, Willan AR, Hewson SA, Ohlsson A, Kelly EN, Matthews SG, Saigal S, Asztalos E, Ross S, Delisle MF, Amankwah K, Guselle P, Gafni A, Lee SK, Armson BA; MACS Collaborative Group. Lancet. 2008 Dec 20;372(9656):2143-51. doi: 10.1016/S0140-6736(08)61929-7. https://www.ncbi.nlm.nih.gov/pubmed/19101390
2. Maternal side-effects after multiple courses of antenatal corticosteroids (MACS): the three-month follow-up of women in the randomized controlled trial of MACS for preterm birth study. Murphy KE, Hannah ME, Willan AR, Ohlsson A, Kelly EN, Matthews SG, Saigal S, Asztalos E, Ross S, Delisle MF, Tomat L, Amankwah K, Guselle P, Gafni A, Lee SK, Armson BA; MACS Collaborative Group.J Obstet Gynaecol Can. 2011 Sep;33(9):909-21.
   https://www.ncbi.nlm.nih.gov/pubmed/21923988
3. Multiple courses of antenatal corticosteroids for preterm birth study: 2-year outcomes. Asztalos EV, Murphy KE, Hannah ME, Willan AR, Matthews SG, Ohlsson A, Kelly EN, Saigal S, Ross S, Delisle MF, Amankwah K, Guselle P, Gafni A, Lee SK, Armson BA, Sananes R, Tomat L; Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study Collaborative Group. Pediatrics. 2010 Nov;126(5):e1045-55. doi: 10.1542/peds.2010-0857. Epub 2010 Oct 18. https://www.ncbi.nlm.nih.gov/pubmed

MACS-5 – Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study: Outcomes in Children at 5 Years of Age

Principal investigator

Dr. Elizabeth Asztalos, Sunnybrook Health Sciences Centre

Summary

This is the follow up study of children born to participants of the MACS trial. All children alive at 5 years of age underwent the five-year assessment, which included a neurologic assessment to determine the presence of cerebral palsy and any hearing/visual difficulties and the completion of two parent questionnaires. The institutions were encouraged to contact the families of all surviving children even if no contact had been made at 18 to 24 months of age. The target date for the visit was the child’s fifth chronological birthday; completing the assessments within four months of the target date was encouraged, but efforts to locate and assess the children continued beyond this age when necessary.

Intervention: Single and multiple courses of antenatal corticosteroid therapy.

The primary outcome was a composite of death or survival with a neurodevelopmental disability in at least one of the following domains: neuromotor (nonambulatory cerebral palsy), neurosensory (blindness, deafness, or need for visual or hearing aids), or neurocognitive/neurobehavioural function (abnormal attention, memory, or behaviour).

1728 children participated and 1719 children contributed to the primary outcome.

ClinicalTrials.gov (NCT#)

NCT00187382

Trial email

macs@sw.ca

Trial locations

80

Publications

Multiple courses of antenatal corticosteroids for preterm birth study: outcomes in children at 5 years of age (MACS-5). Asztalos EV, Murphy KE, Willan AR, Matthews SG, Ohlsson A, Saigal S, Armson BA, Kelly EN, Delisle MF, Gafni A, Lee SK, Sananes R, Rovet J, Guselle P, Amankwah K, Saleem M, Sanchez J; MACS-5 Collaborative Group. JAMA Pediatr. 2013 Dec;167(12):1102-10. doi: 10.1001/jamapediatrics.2013.2764. https://www.ncbi.nlm.nih.gov/pubmed

MiTy – Metformin in Women With Type 2 Diabetes in Pregnancy Trial)

Principal investigator

Dr. Denice Feig, Mount Sinai Hospital

Summary

The trial was a phase III, multi-site, randomized, double-masked placebo-controlled trial of metformin or placebo in addition to their usual insulin regimen, in women diagnosed with type 2 diabetes in pregnancy, between 6+0 and 22+6 weeks gestation. The analysis was conducted using an intention-to-treat approach.

ClinicalTrials.gov (NCT#)

NCT01353391

Trial email

MiTy@sunnybrook.ca

Trial locations

29

Primary outcome: a composite of pregnancy loss (miscarriage, termination, stillbirth, neonatal death), preterm birth, birth injury, moderate/severe respiratory distress, neonatal hypoglycemia, and NICU admission > 24 hours.

Sample size: 502

Publications

Feig DS, Murphy K, Asztalos E, Tomlinson G, Sanchez J, Zinman B, Ohlsson A, Ryan EA, Fantus IG, Armson AB, Lipscombe LL, Barrett JF; MiTy Collaborative Group. Metformin in women with type 2 diabetes in pregnancy (MiTy): a multi-center randomized controlled trial. BMC Pregnancy Childbirth. 2016 Jul 19;16(1):173. doi: 10.1186/s12884-016-0954-4.

Feig DS, Donovan LE, Zinman B, Sanchez JJ, Asztalos E, Ryan EA, Fantus IG, Hutton E, Armson AB, Lipscombe LL, Simmons D, Barrett JFR, Karanicolas PJ, Tobin S, McIntyre HD, Tian SY, Tomlinson G, Murphy KE; MiTy Collaborative Group. Metformin in women with type 2 diabetes in pregnancy (MiTy): a multicentre, international, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2020 Oct;8(10):834-844. doi: 10.1016/S2213-8587(20)30310-7. Erratum in: Lancet Diabetes Endocrinol. 2020 Nov;8(11):e6. PMID: 32946820.

MiTy Kids – Metformin in Women with Type 2 Diabetes in Pregnancy Kids Trial

Principal investigator

Dr. Denice Feig, Mount Sinai Hospital

Summary

MiTy Kids is an international, multi-centre follow up study to the MiTy Trial. The trial seeks to determine whether treatment with metformin during pregnancy, in women with type 2 diabetes, leads to a reduction in adiposity as measured by BMI z-score and sum of skinfold thickness in the offspring at 2 years of age.

ClinicalTrials.gov (NCT#)

NCT01832181

Trial email

MiTyKids@sunnybrook.ca

Trial locations

CANADA: Toronto, Ontario; London, Ontario; Ottawa, Ontario; Kingston, Ontario; Halifax, Nova Scotia; Montreal, Quebec; Quebec City, Quebec; Winnipeg, Manitoba; Edmonton, Alberta; Calgary, Alberta; Vancouver, British Columbia; Victoria, British Columbia, St. John’s, Newfoundland; Regina, Saskatchewan; AUSTRALIA: Campbelltown, New South Wales, Australia; Brisbane, Queensland, Australia.

The term breech trial (TBT) – Planned caesarean section versus planned vaginal birth for breech presentation at term: a randomised multicentre trial

Principal investigator

Mary Hannah

Summary

For 3-4 per cent of pregnancies, the fetus will be in the breech presentation at term. For most of these women, the approach to delivery is controversial. We did a randomised trial to compare a policy of planned caesarean section with a policy of planned vaginal birth for selected breech-presentation pregnancies.

Women with a singleton fetus in a frank or complete breech presentation were randomly assigned planned caesarean section or planned vaginal birth. Women having a vaginal breech delivery had an experienced clinician at the birth. Mothers and infants were followed-up to six weeks post partum.

The primary outcomes were perinatal mortality, neonatal mortality, or serious neonatal morbidity; and maternal mortality or serious maternal morbidity.

2088 patients were enrolled in this study

Trial locations

121 centres in 26 countries

Publications

Planned caesarean section versus planned vaginal birth for breech presentation at term: a randomised multicentre trial. Term Breech Trial Collaborative Group. Hannah ME, Hannah WJ, Hewson SA, Hodnett ED, Saigal S, Willan AR. Lancet. 2000 Oct 21;356(9239):1375-83. https://www.ncbi.nlm.nih.gov/pubmed/11052579

TBS – Twin Birth Study

Principal investigator

Dr. Jon Barrett, Sunnybrook Health Sciences Centre

Summary

Twins complicate approximately 2-3 per cent of all births. Twin fetuses that are >2500g at birth are at higher risk of death and neonatal morbidity than singletons of the same birth weight. In addition, the second twin is at higher risk of death and/or serious neonatal morbidity compared with twin A if delivery is vaginal but not if delivery is by caesarean section (CS).
The study aimed to conduct an international multicentre RCT, comparing planned CS to planned VB for twins at 32 to 38 weeks gestation.
Because there is an increase in stillbirth rate after 38 weeks gestation, trial participants were delivered by the planned method of delivery at 38 weeks. Vaginal delivery was conducted by experienced personnel: if twin B is non-vertex the initial options for delivery were: spontaneous or assisted vaginal breech delivery (if breech); total breech extraction with or without internal podalic version; or external cephalic version and vaginal delivery of the fetus as a vertex.

Primary outcomes: Perinatal or neonatal mortality and/or serious neonatal morbidity (excluding lethal congenital anomalies).

Secondary outcomes: death or poor neurodevelopmental outcome of the children at 2 years of age; problematic urinary or fecal/flatal incontinence for the mother at two years postpartum.

Other outcomes: maternal death or serious maternal morbidity within 28 days following delivery; maternal satisfaction with method of delivery (three months); breast feeding (three months); maternal quality of life (three months and two years); problematic urinary or fecal/flatal incontinence at three months

Sample size: 2804 women

ClinicalTrials.gov (NCT#)

NCT00187369

Trial email

TBS@sunnybrook.ca

Trial locations

106 centres in 25 countries.

Publications

1. Barrett JFR, Hannah ME, Hutton EK, Willan AR, Allen AC, Armson BA, Gafni A, Joseph KS, Mason D, Ohlsson A, Ross S, Sanchez JJ, Asztalos EV, Twin Birth Study Collaborative Group. A Randomized Trial of Planned Cesarean or Vaginal Birth Delivery for Twin Pregnancy. N Engl J Med 2013; 369: 1295-305. Doi:10.1056/NEJMoa1214939. PMID: 24088091.
2. Hutton EK, Hannah ME, Ross S, Joseph KS, Ohlsson A, Asztalos EV, Willan AR, Allen AC, Armson BA, Gafni A, Mangoff K, Sanchez JJ, Barrett JF; Twin Birth Study Collaborative Group. Maternal outcomes at 3 months after planned caesarean section versus planned vaginal birth for twin pregnancies in the Twin Birth Study: a randomised controlled trial. BJOG. 2015 Nov;122(12):1653-62.
3. Asztalos EV, Hannah ME, Hutton EK, Willan AR, Allen AC, Armson BA, Gafni A, Joseph KS, Ohlsson A, Ross S, Sanchez JJ, Mangoff, K and Barrett JFR for Twin Birth Study Collaborative Group. Twin Birth Study: 2-year neurodevelopmental follow-up of the randomized trial comparing planned cesarean vs planned vaginal delivery for twin pregnancy. Am J Obstet Gynecol. 2016 Jan; 214(3):371.e – 371.e19.
4. Hutton EK, Hannah ME, Willan AR, Ross S, Allen AC, Armson BA, Gafni A, Joseph KS, Mangoff K, Ohlsson A, Sanchez JJ, Asztalos EV, Barrett J; Twin Birth Study Collaborative Group. Urinary stress incontinence and other maternal outcomes 2 years after caesarean or vaginal birth for twin pregnancy: a multicentre randomised trial. BJOG. 2018 Dec;125(13):1682-1690. doi: 10.1111/1471-0528.15407. Epub 2018 Aug 27.

CALM-IT – CAnnabinoid Liquid Medication Intervention Trial

Principal investigators

Dr. Krista Lanctôt, PhD, Sunnybrook Health Sciences Centre

Summary

The CALM-IT trial is a randomized, double-blind, placebo-controlled cross-over clinical trial which will assess the safety and efficacy of JZP541 (a botanical cannabinoid drug) for managing agitation in patients with Alzheimer’s disease and will identify novel biomarkers of agitation severity and treatment response.

60 participants will be enrolled in this trial.

ClinicalTrials.gov (NCT#)

NCT06014424

Trial email

CALM-IT@sunnybrook.ca

Trial locations

• Toronto, ON, Canada
• Oshawa, ON, Canada
• Calgary, AB, Canada

NAB-IT – Nabilone for Agitation Blinded Intervention Trial

Principal investigators

Dr. Krista Lanctôt, PhD, Sunnybrook Health Sciences Centre

Recruitment status

Recruiting

Summary

NAB-IT is a randomized, double-blind, placebo-controlled clinical trial. The overall sample size of the study will be 112. Participants should have a diagnosis of Alzheimer’s disease (AD), with clinically significant agitation.
The primary objective is to assess the efficacy of nabilone in participants with AD in the treatment of agitation, as measured by the Cohen-Mansfield Agitation Inventory (CMAI), compared to placebo. Nabilone is approved by Health Canada for managing severe nausea and vomiting in patients receiving chemotherapy. It is a medication based on tetrahydrocannabinol (THC), one substance in cannabis.
Participants in this study will randomly be assigned to receive either nabilone (up to 2 mg/day) or a placebo for 9 weeks. In addition to looking at agitation, the researchers will also look at whether participants will benefit in other ways, including overall behavioural symptoms, caregiver distress, thinking and memory, nutritional status, and pain.

ClinicalTrials.gov (NCT#)

NCT04516057

Trial email

NAB-IT@Sunnybrook.ca

Trial locations

• Toronto, ON, Canada
• Whitby, ON, Canada
• Calgary, AB, Canada

Links

Toronto Dementia Network Study Page

BOOST KIDNEY – BOOST KIDNEY: A Multi-Centre 12 Month Parallel-Group Randomized Control Trial of BNT162b2 versus mRNA-1273 COVID-19 Vaccine Boosters in Chronic Kidney Disease and Dialysis Patients with Poor Humoral Response following COVID-19 Vaccination

Principal investigator

Dr. Michelle Hladunewich, Sunnybrook Health Sciences Centre

Summary

Chronic kidney disease (CKD) affects more than 10 per cent of Canadians. CKD patients, especially those receiving dialysis, are highly susceptible to infections, and SARS-CoV-2 infections in this group have been more severe than in the general population leading to frequent hospitalizations and higher mortality rates. Often, people with CKD have a weaker response to traditional vaccines so they may remain vulnerable to COVID-19.

BOOST KIDNEY is a parallel, randomized controlled trial aiming at studying whether third dose BNT162b2 or mRNA-1273 for the third dose results in differences in vaccine-induced immune responses. Participants are randomized to receive either BNT162b2 or mRNA-1273 as a third dose booster. Blood is collected at 1, 3, 6, 9 and 12 months post booster to measure the serologic response.

Sample size: 273 Chronic Kidney Disease and dialysis patients.

Intervention: BNT162b2 (Pfizer) and mRNA-1273 (Moderna) COVID-19 Vaccines.

ClinicalTrials.gov (NCT#)

NCT05022329

Trial email

COVID-CKD@sunnybrook.ca

Trial locations

• Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
• Toronto General Hospital, Toronto, Ontario, Canada
• Scarborough General Hospital, Scarborough, Ontario, Canada

COVID-CKD (Observational Study) – Determining the Safety and Efficacy of COVID-19 Vaccination in the Chronic Kidney Disease Population

Principal investigator

• Dr. Matthew Oliver, Sunnybrook Health Sciences Centre
• Dr. Michelle Hladunewich, Sunnybrook Health Sciences Centre
• Dr. Adeera Levin, University of British Columbia

Summary

Chronic kidney disease (CKD) affects more than 10 per cent of Canadians. CKD patients, especially those receiving dialysis, are highly susceptible to infections, and SARS-CoV-2 infections in this group have been more severe than in the general population leading to frequent hospitalizations and higher mortality rates. Often, people with CKD have a weaker response to traditional vaccines so they may remain vulnerable to COVID-19.

This observational study aims to determine if COVID-19 vaccines generate adequate immune response in this population and how well the vaccines prevent COVID-19 infection.

Sample size: 2337

Intervention: None, observational

Primary Outcomes:
To determine the safety and serological response to COVID-19 vaccination, as well as potential booster shots, among individuals with CKD stages 3b, 4 and 5.

Trial email

COVID-CKD@sunnybrook.ca

Trial locations

Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
Toronto General Hospital, Toronto, Ontario, Canada
St. Michael ‘s Hospital, Toronto, Ontario, Canada
Michael Garron Hospital, Toronto, Ontario, Canada
St. Paul‘s Hospital, Vancouver, British Columbia, Canada

Publications

Yau K, Abe KT, Naimark D, Oliver MJ, Perl J, Leis JA, Bolotin S, Tran V, Mullin SI, Shadowitz E, Gonzalez A, Sukovic T, Garnham-Takaoka J, de Launay KQ, Takaoka A, Straus SE, McGeer AJ, Chan CT, Colwill K, Gingras AC, Hladunewich MA. Evaluation of the SARS-CoV-2 Antibody Response to the BNT162b2 Vaccine in Patients Undergoing Hemodialysis. JAMA Netw Open. 2021 Sep 1;4(9):e2123622. doi: 10.1001/jamanetworkopen.2021.23622. PMID: 34473256; PMCID: PMC8414193. https://pubmed.ncbi.nlm.nih.gov/34473256/

Oliver MJ, Thomas D, Balamchi S, Ip J, Naylor K, Dixon SN, McArthur E, Kwong J, Perl J, Atiquzzaman M, Singer J, Yeung A, Hladunewich M, Yau K, Garg AX, Leis JA, Levin A, Krajden M, Blake PG. Vaccine Effectiveness Against SARS-CoV-2 Infection and Severe Outcomes in the Maintenance Dialysis Population in Ontario, Canada. J Am Soc Nephrol. 2022 Apr;33(4):839-849. doi: 10.1681/ASN.2021091262. Epub 2022 Mar 9. PMID: 35264455; PMCID: PMC8970446. https://pubmed.ncbi.nlm.nih.gov/35264455/

Oliver MJ, Blake PG. Clinical Utility of COVID-19 Vaccination in Patients Undergoing Hemodialysis. Clin J Am Soc Nephrol. 2022 Jun;17(6):779-781. doi: 10.2215/CJN.04930422. PMID: 35649720; PMCID: PMC9269653. https://pubmed.ncbi.nlm.nih.gov/35649720/

Colwill K, Galipeau Y, Stuible M, Gervais C, Arnold C, Rathod B, Abe KT, Wang JH, Pasculescu A, Maltseva M, Rocheleau L, Pelchat M, Fazel-Zarandi M, Iskilova M, Barrios-Rodiles M, Bennett L, Yau K, Cholette F, Mesa C, Li AX, Paterson A, Hladunewich MA, Goodwin PJ, Wrana JL, Drews SJ, Mubareka S, McGeer AJ, Kim J, Langlois MA, Gingras AC, Durocher Y. A scalable serology solution for profiling humoral immune responses to SARS-CoV-2 infection and vaccination. Clin Transl Immunology. 2022 Mar 23;11(3):e1380. doi: 10.1002/cti2.1380. PMID: 35356067; PMCID: PMC8942165. https://pubmed.ncbi.nlm.nih.gov/35356067/

Yau K, Chan CT, Abe KT, Jiang Y, Atiquzzaman M, Mullin SI, Shadowitz E, Liu L, Kostadinovic E, Sukovic T, Gonzalez A, McGrath-Chong ME, Oliver MJ, Perl J, Leis JA, Bolotin S, Tran V, Levin A, Blake PG, Colwill K, Gingras AC, Hladunewich MA. Differences in mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 vaccine immunogenicity among patients undergoing dialysis. CMAJ. 2022 Feb 28;194(8):E297-E305. doi: 10.1503/cmaj.211881. Epub 2022 Feb 3. PMID: 35115375; PMCID: PMC9053976. https://pubmed.ncbi.nlm.nih.gov/35115375/

Atiquzzaman M, Zheng Y, Er L, Djurdjev O, Singer J, Krajden M, Balamchi S, Thomas D, Oliver MJ, Levin A. COVID-19 vaccine effectiveness in patients with non-dialysis-dependent chronic kidney diseases: findings from a population-based observational study from British Columbia, Canada. Kidney Int. 2022 Dec;102(6):1420-1423. doi: 10.1016/j.kint.2022.08.027. Epub 2022 Sep 11. PMID: 36103954; PMCID: PMC9464316. https://pubmed.ncbi.nlm.nih.gov/36103954/

McEvoy CM, Hu Q, Abe KT, Yau K, Oliver MJ, Levin A, Gingras AC, Hladunewich MA, Yuen DA. Humoral Responses in the Omicron Era Following 3-Dose SARS-CoV-2 Vaccine Series in Kidney Transplant Recipients. Transplant Direct. 2022 Dec 7;9(1):e1401. doi: 10.1097/TXD.0000000000001401. PMID: 36518793; PMCID: PMC9742098. https://pubmed.ncbi.nlm.nih.gov/36518793/

Yau K, Enilama O, Levin A, Romney MG, Singer J, Blake P, Perl J, Leis JA, Kozak R, Tsui H, Bolotin S, Tran V, Chan CT, Tam P, Dhruve M, Kandel C, Estrada-Codecido J, Brown T, Siwakoti A, Abe KT, Hu Q, Colwill K, Gingras AC, Oliver MJ, Hladunewich MA. Determining the Longitudinal Serologic Response to COVID-19 Vaccination in the Chronic Kidney Disease Population: A Clinical Research Protocol. Can J Kidney Health Dis. 2023 Mar 20;10:20543581231160511. doi: 10.1177/20543581231160511. PMID: 36950028; PMCID: PMC10028441. https://pubmed.ncbi.nlm.nih.gov/36950028/

Wing S, Thomas D, Balamchi S, Ip J, Naylor K, Dixon SN, McArthur E, Kwong JC, Perl J, Atiquzzaman M, Yeung A, Yau K, Hladunewich MA, Leis JA, Levin A, Blake PG, Oliver MJ. Effectiveness of Three Doses of mRNA COVID-19 Vaccines in the Hemodialysis Population during the Omicron Period. Clin J Am Soc Nephrol. 2023 Apr 1;18(4):491-498. doi: 10.2215/CJN.0000000000000108. Epub 2023 Mar 2. PMID: 36723290. https://pubmed.ncbi.nlm.nih.gov/36723290/

Roushani J, Thomas D, Oliver MJ, Ip J, Yeung A, Tang Y, Brimble KS, Levin A, Hladunewich MA, Cooper R, Blake PG. Clinical Outcomes and Vaccine Effectiveness for SARS-CoV-2 Infection in People Attending Advanced CKD Clinics: A Retrospective Provincial Cohort Study. Clin J Am Soc Nephrol. 2023 Apr 1;18(4):465-474. doi: 10.2215/CJN.0000000000000087. Epub 2023 Feb 16. PMID: 36795940. https://pubmed.ncbi.nlm.nih.gov/36795940/

PITSTOP RCT – Paramedic Initiated Treatment of Sepsis Targeting Out-of-Hospital Patients Randomized Controlled Trial

Principal investigator

Dr. Damon Scales, Sunnybrook Health Sciences Centre

Recruitment status

Recruiting

Summary

The PITSTOP RCT is a pragmatic 2×2 factorial randomized controlled trial that will test whether prompt recognition of sepsis by paramedics in the field followed by (1) early intramuscular antibiotics versus placebo and/or (2) early liberal intravenous fluids versus usual fluid management leads to more lives saved.

The study involves the administration of Ceftriaxone by intramuscular injection or placebo comprised of 0.9% NaCl (sodium chloride). Ceftriaxone is approved by Health Canada and all study procedures follow the recommendations of the approved product monograph. The study also involves the administration of 2 litres of intravenous 0.9% NaCl (sodium chloride) regardless of blood pressure, compared to usual IV fluid administration according to the standard Medical Directive.

The trial intervention will be delivered by paramedics working in participating Emergency Medical Services: currently Peel and Halton in Ontario, with plans to add additional services across Canada. The primary outcome for the trial is hospital survival. The anticipated sample size is 2040 patients recruited over a 4 to 5 year period.

ClinicalTrials.gov (NCT#)

NCT03068741

Trial email

pitstop@sunnybrook.ca

Trial locations (city, province, country)

Halton, Peel and Toronto Paramedic Services

Social media links

X

TESTING-ON – Therapeutic Evaluation of STeroids in IgA Nephropathy Global – Post-Trial ObservatioNal

Principal investigator

Dr. Michelle Hladunewich, Sunnybrook Health Sciences Centre

Recruitment status

Recruiting

Summary

TESTING-ON is the follow up of the TESTING study where participants were given a 6–9-month course of oral methylprednisolone (a steroid). The purpose of this study is to evaluate the long-term effects and safety of oral methylprednisolone given with routine treatment, at preventing kidney failure in patients who have IgA nephropathy and are at high risk of progression to end stage kidney disease (ESKD)

The trial Primary Objective is to determine if adding methylprednisolone to optimal background care reduces the risk of kidney failure, defined as a composite of end-stage kidney disease (ESKD), a 40% reduction in eGFR or death due to kidney disease, in patients with progressive IgA nephropathy

Approximately 366 people are estimated to participate.

ClinicalTrials.gov (NCT#)

NCT05434325

Trial email

testingstudy@sunnybrook.ca

Trial locations

Toronto, ON; London, ON; Montreal; QC; Vancouver, BC;

TESTING – Therapeutic Evaluation of STeroids in IgA Nephropathy Global low dose

Principal investigator

Dr. Michelle Hladunewich, Sunnybrook Health Sciences Centre

Summary

A multi-centre randomized double-blinded study to evaluate the long-term efficacy and safety of low dose oral methylprednisolone compared to matching placebo, on a background of routine RAS inhibitor therapy, in preventing kidney events in patients with IgA nephropathy and features suggesting a high risk of progression.

Primary outcomes were:

• Change in proteinuria from baseline at 6th and 12th months
• Mean change in eGFR at 6th and 12th months
• Progressive kidney failure, which is a composite of a 40 per cent decrease in eGFR, the development of end stage kidney disease (ESKD) defined as a need for maintenance dialysis or kidney transplantation, and death due to kidney disease
• Primary outcome specifically for the low-dose cohort

503 patients were enrolled in the study.

ClinicalTrials.gov (NCT#)

NCT01560052

Trial email

testingstudy@sunnybrook.ca

Trial locations

67 sites (Canada – 8, Australia – 5, China – 41, India – 6, Malaysia – 6, Hong Kong – 1)

Publications

1. Lv J, Zhang H, Wong MG, Jardine MJ, Hladunewich M, Jha V, Monaghan H, Zhao M, Barbour S, Reich H, Cattran D, Glassock R, Levin A, Wheeler D, Woodward M, Billot L, Chan TM, Liu ZH, Johnson DW, Cass A, Feehally J, Floege J, Remuzzi G, Wu Y, Agarwal R, Wang HY, Perkovic V; TESTING Study Group. Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial. JAMA. 2017 Aug 1;318(5):432-442. doi: 10.1001/jama.2017.9362. https://pubmed.ncbi.nlm.nih.gov/28763548/ 
2. Yeo SC, Liew A, Barratt J. Emerging therapies in immunoglobulin A nephropathy. Nephrology (Carlton). 2015 Nov;20(11):788-800. doi: 10.1111/nep.12527. https://pubmed.ncbi.nlm.nih.gov/26032537/

TILE – The TILE Pilot Study – Tinzaparin Lead‐In to Prevent the Post‐Thrombotic Syndrome Phase IV Study

Principal investigators

Dr Jean-Philippe Galanaud, Sunnybrook Health Sciences Centre

Recruitment status

Terminated (Halted Prematurely)

Summary

The TILE study will be a multicenter, open‐label, assessor‐blinded RCT to assess whether a 3-week course of tinzaparin plus DOAC (Direct Oral Anticoagulants, rivaroxaban) is superior to DOAC alone to prevent post thrombotic syndrome after a first acute common femoral or iliac DVT. The TILE pilot study is a multicenter, open‐label, assessor‐blinded pilot RCT that will assess whether performing such a study is feasible and to determine the sample size of the definitive study. 60 participants will be enrolled in this trial.

ClinicalTrials.gov (NCT#)

NCT04794569

Trial email

tile@sunnybrook.ca

Trial locations

Hamilton, Toronto & Ottawa, Ontario; Montreal, Quebec

CLEAN Joint Trial – CLinical Evaluation of ANtiseptic Skin Preparation in Revision Total Joint Arthroplasty of the Hip and Knee – A Vanguard Randomized Controlled Registry Trial

Principal investigator

Dr. Raman Mundi, Sunnybrook Health Sciences

Recruitment status

Recruiting

Summary

The CLEAN Joint trial is a pragmatic, open label, 2-arm parallel-group pilot randomized controlled trial that is planned to simulate all aspects of a larger definitive trial. Patients scheduled to undergo aseptic revision THA or revision TKA will be randomly assigned to receive surgical antiseptic skin preparation with either chlorhexidine or iodine-based solution.

The main outcome of interest is the need for re-operation for a wound complication or an infection of the prosthetic joint within one year after surgery. Other key outcomes are surgical site infection, mortality, and readmission to hospital.

ClinicalTrials.gov (NCT#)

NCT05828810

Trial email

CLEANJoint@sunnybrook.ca

Trial locations

Toronto, ON, Canada

IMPACTS – The Innovative, Multicentre, Patient-centred Approach to Clinical Trials in Surgery (IMPACTS) Program

Principal investigator

Dr Paul Karanicolas, Sunnybrook Health Sciences Centre

Recruitment status

Recruiting

Summary

IMPACTS is a platform of pragmatic trials that are integrated into routine clinical care. Key elements of the methodology include: enrollment using an integrated consent model that incorporates oral consent, leveraging of existing data collection registries to minimize additional data collection, patient-reported outcome measures, and an adaptive design that allows for removal of arms and stopping of the trial when efficacy or equivalence targets are met.

The IMPACTS pilot trials aim to demonstrate feasibility of the platform according to pre-defined objectives related to enrollment, ability to deliver the interventions, and collect outcome data. The trials are:

The CLEAN Wound Trial

This trial aims to determine if intraoperative incisional wound irrigation with povidone-iodine solution or saline prevents surgical site infections when compared to no irrigation.

The ICE Trial

This study examines whether cryotherapy (cold therapy) improves the quality of patients’ post-operative recovery and pain compared to no cryotherapy.

The COFFEE Trial

This trial aims to determine if coffee/caffeine can improve post-operative gastrointestinal recovery.

PARFAIT

This trial examines whether the use of antibiotics prevents fistula formation in patients with perianal abscesses following incision and drainage.

Trial email

impactsprogram@sunnybrook.ca

Trial Locations

• Toronto, ON, Canada
• Ottawa, ON, Canada

Links

Study Website
X Profile

1. CLEAN Wound Trial: NCT04548661
2. ICE Trial: NCT04564963
3. COFFEE Trial: NCT04547868
4. PARFAIT: NCT04549311

PERQ-UP – Pancreatic Enzyme Replacement Therapy to Improve Quality of Life in Patients Undergoing Pancreaticoduodenectomy: A Pilot Randomized Controlled Trial

Principal investigator

Dr Paul Karanicolas, Sunnybrook Health Sciences Centre

Recruitment status

Recruiting

Summary

PERQ-UP is a pilot, multi-centre, pragmatic randomized controlled trial that is planned to simulate all aspects of a larger definitive trial comparing early initiation of pancreatic enzyme replacement therapy (PERT) immediately after pancreaticoduodenectomy (PD) versus standard of care initiation of PERT upon symptom presentation for the treatment of pancreatic enzyme insufficiency (PEI), in appropriately selected patients.

The primary outcome measures for the pilot trial are to determine feasibility. Specifically, to: 1) determine the proportion of patients screened who meet eligibility criteria and consent; 2) assess adherence with PERT after 3-months; 3) assess adherence with PERT dosing guidelines; 4) examine our ability to collect complete perioperative and follow-up data to 3-months; and 5) determine resource requirements to conduct a definitive trial. The pilot aims to enroll 100 participants across 6 sites in Ontario. The definitive study will enroll an additional 300 participants across Canada.

ClinicalTrials.gov (NCT#)

NCT05466838

Trial email

PERQ-UP@sunnybrook.ca

Trial locations

Toronto, Ontario; Hamilton, Ontario; London, Ontario; Kingston, Ontario; Ottawa, Ontario

PRIMe – The HepatoPancreaticoBiliary Resection Arginine Immunomodulation

(PRIMe) Trial: A Randomized Phase II Trial of the Impact of Perioperative Immunomodulation on Immune

Function following Resection for HepatoPancreaticoBiliary Malignancy

Principal investigator

Dr Paul Karanicolas, Sunnybrook Health Sciences Centre

Recruitment status

Completed

Summary

This is a randomized controlled blinded superiority trial to evaluate the impact of perioperative immunosupplementation on NK-cell function following resection of HPB malignancies. Two variations of immunosupplementation will be compared to control nutritional supplement containing whey protein with an additional tsp of placebo oil. These variations will be 1) a powdered formula containing whey protein and arginine (Active A) with an additional teaspoon (tsp) of lipid bolus containing omega-3 fatty acids, and 2) a powdered formula containing whey protein and arginine (Active A) with an additional tsp of placebo oil which does not contain omega-3 fatty acids. 45 participants will be enrolled.

The primary outcome is reduction in NK cell killing as measured on post-operative day 1 as compared to baseline (pre-operative) between the control and experimental cohorts. A flow cytometry-based killing assay will be used which can specifically measure NK cell cytotoxicity by utilizing fluorescent cell dyes to distinguish between live or dead Effector cells (the patient PBMCs or the control NK92 cell line) and target cells (the K562 erythroleukemia cell line). Arginine supplementation will be considered effective at reducing postoperative NK cell dysfunction if there is a 50% or greater improvement in postoperative suppression of NK cell cytotoxicity (reduction of 27% from baseline).

ClinicalTrials.gov (NCT#)

NCT04549662

Trial email

PRIME@sunnybrook.ca

Trial locations

Toronto & Ottawa, Ontario