Canadian Critical Care Comparative Effectiveness Platform (CEPEC)

Canadian Critical Care Comparative Effectiveness Platform(e) d'Évaluation Clinique Comparée en Soins Critiques (CEPEC)

The Canadian Critical Care Comparative Effectiveness Platform(e) d'Évaluation Clinique Comparée en soins Critiques (CEPEC) is an international multi-centered randomized adaptive platform clinical trial. CEPEC will evaluate supportive care interventions that are used routinely in intensive care units throughout the world.

Study Overview

• Status: Recruiting
• Conditions: Platelet; Nutrition; Vasopressor; Intensive Care Unit ICU
• Intervention / Treatment: Drug: 1- Vasopressor - Mean arterial pressure 56-60; Drug: 2- Vasopressor - Mean arterial pressure 61-65; Drug: 3- Vasopressor - Mean arterial pressure 66-70; Drug: 4- Vasopressor - Mean arterial pressure 71-75; Other: 1- Platelet less than 10 x 109/L; Other: 2- Platelet less than 20 x 109/L; Other: 3- Platelet less than 30 x 109/L; Other: 4- Platelet less than 40 x 109/L; Other: 5- Platelet less than 50 x 109/L; Other: Enteral nutrition - Boluses; Other: Enteral nutrition - Continuous

Detailed Description

Many supportive therapies used daily in the ICU setting remain under-studied despite being resource-intensive. CEPEC aims to incorporate domains evaluating vasopressors, platelets, nutrition, sedation and analgesia, and other interventions.

VASOPRESSOR DOMAIN The investigators will investigate whether vasoactive medications should be used differently for different subgroups of patients who are in a state of cardiovascular shock (i.e. heterogeneity of treatment effects). Vasoactive medications are common in critically ill patients, and have considerable patient, hospital, and health system resource impact, but their use remains poorly supported by scientific evidence.

PLATELET DOMAIN Platelet transfusions are commonly prescribed to critically ill patients and have considerable patient, hospital, and health system resource impact, but remain poorly supported by scientific evidence. We propose to join a multicentre randomized clinical trial (T4P, ISRCTN79371664) addressing the optimal use of platelet transfusions for critically ill patients with thrombocytopenia in advance of invasive procedures. A multinational collaboration will ensure timely completion of this high-impact multicentre randomized clinical trial. The Canadian component of the T4P trial is embedded in the CEPEC platform as the Platelet Domain.

NUTRITION DOMAIN Most critically ill patients cannot eat normally and require a specialized method of feeding, called enteral nutrition. It is provided every hour around the clock. This differs from how we usually eat, with meals (boluses) divided over the day while we are awake. The goals of this study are to determine if a large study can be successfully done comparing nutrition given 3 times a day (boluses) compared to given in small amounts every hour (continuously).

• Study Type: Interventional
• Enrollment (Estimated): 5500
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Marie-Helene Masse, RRT, MSc; Phone Number: 14173 1-819-346-1110; Email: marie-helene.masse3@usherbrooke.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 1C3
      • Recruiting
      • Hamilton Health Sciences - Juravinski Hospital
      • Contact: Tina Millen; Phone Number: 905-521-2100; Email: millent@mcmaster.ca
      • Principal Investigator: Bram Rochwerg
    • Ottawa, Ontario, Canada, K1H 8L6
      • Recruiting
      • The Ottawa Hospital
      • Contact: Irene Watpool; Phone Number: 613-737-8724; Email: iwatpool@ohri.ca
      • Principal Investigator: Alexandre Tran
    • Scarborough Village, Ontario, Canada, M1P 2V5
      • Recruiting
      • Scarborough Health Network
      • Contact: Joshua Craig; Phone Number: 416-438-2911; Email: jcraig@shn.ca
      • Principal Investigator: Christopher Yarnell
    • St. Catharines, Ontario, Canada, L2S 0A9
      • Recruiting
      • Niagara Health
      • Principal Investigator: Jennifer Tsang
      • Contact: Jennifer Tsang; Phone Number: 905-684-7271; Email: jennifer.tsang@mail.utoronto.ca
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Sunnybrook Health Sciences Centre
      • Contact: Nicole Marinoff; Phone Number: 416-480-4522; Email: Nicole.Marinoff@sunnybrook.ca
      • Principal Investigator: Neill Adhikari
  • Quebec
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Recruiting
      • CIUSSS de l'Estrie - CHUS
      • Contact: Marie-Helene Masse, RRT, MSc; Phone Number: 14173 819-346-1110; Email: marie-helene.masse3@usherbrooke.ca
      • Principal Investigator: Francois Lamontagne
      • Contact: Monica Sean, PhD; Phone Number: 14266 819-346-1110; Email: monica.sean@usherbrooke.ca
• New Zealand
  • Auckland, New Zealand
    • Not yet recruiting
    • Auckland City Hospital
• United Kingdom
  • London, United Kingdom
    • Not yet recruiting
    • Intensive Care National Audit and Research Centre (coordinating centre for sites in UK. Sites to be determined)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

VASOPRESSOR DOMAIN There is no minimum age limit in the Vasopressor Domain.

Inclusion criteria:

1. Ongoing vasopressor infusion to treat hypotension, or would be used to treat clinician-defined hypotension as part of usual care;
2. MAP <75 mmHg at any point (or lower than the upper value of the highest mean arterial pressure (MAP) target range activated locally);
3. Patient expected to be in the ICU for >48 hours.

Exclusion criteria:

1. Treating team does not have equipoise for at least two contiguous MAP target ranges in the CEPEC Vasopressor Domain;
2. Acute traumatic brain injury (within 7 days days or ongoing active treatment for elevated intracranial pressure);
3. Acute subarachnoid hemorrhage (within 21 days);
4. Acute spinal cord injury (within 7 days of injury or ongoing vasopressor therapy for suspected spinal cord ischemia);
5. Lung, heart, liver, kidney transplant recipient (within 7 days);
6. More than 24 hours since meeting inclusion criteria in the ICU;
7. Previously randomized into the CEPEC Vasopressor Domain or a confounding trial.

PLATELET DOMAIN

Inclusion criteria:

1. Adult patients (age ≥18 years) admitted to the ICU;
2. Latest platelet count in this hospital admission <50×109/L;
3. Planned to undergo a specified low-moderate bleeding risk invasive procedure.

Exclusion criteria:

1. Ongoing major hemorrhage requiring blood products and/or surgical/radiological intervention;
2. Intracranial hemorrhage within prior 72 hours;
3. Contraindications to platelet transfusion (e.g. thrombotic microangiopathies, heparin-induced thrombocytopenia, recent history of immune thrombocytopaenia, congenital platelet function defects);
4. Known advance decision of refusing blood/blood component transfusions;
5. Acute promyelocytic leukemia (APML);
6. Death perceived as imminent or admission for palliation;
7. Previously randomized into the CEPEC Platelet Domain or the T4P Trial;
8. Fulfilled all the inclusion criteria and none of the exclusion criteria ≥72 hours.

NUTRITION DOMAIN

Inclusion criteria:

1. Critically ill patients ≥18 years of age;
2. Are invasively mechanically ventilated (including endotracheal tube or tracheostomy);
3. Orogastric/nasogastric tube in place; or have an in dwelling percutaneous gastric tube (with confirmed placement);
4. Treating team has started or has the intention of providing enteral nutrition.

Exclusion criteria:

1. Patients who have had gastrointestinal (GI) surgery; in the last 3 months and deemed not ready to receive bolus nutrition;
2. Bowel obstruction or ischemia; active;
3. Has a post-pyloric small bowel feeding tube;
4. Active GI bleeding;
5. Exclude patients who are chronically receiving enteral nutrition.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Vasopressor; Participants will receive vasopressor(s) and their mean arterial pressure will be titrated according to the group they are randomized to (group 1: 56-60 mmHg; group 2: 61-65 mmHg; group 3: 66-70 mmHg; group 4: 71-75 mmHg). Physicians will have the liberty of restricting the randomization to at least 2 contiguous ranges	Drug: 1- Vasopressor - Mean arterial pressure 56-60; Vasopressor(s) will be titrated according to 56-60 range.; Drug: 2- Vasopressor - Mean arterial pressure 61-65; Vasopressor(s) will be titrated according to 61-65 range.; Drug: 3- Vasopressor - Mean arterial pressure 66-70; Vasopressor(s) will be titrated according to 66-70 range.; Drug: 4- Vasopressor - Mean arterial pressure 71-75; Vasopressor(s) will be titrated according to 71-75 range.
Other: Platelet; Thrombocytopenic intensive care unit (ICU) patients (platelet count <50×109/L) with a planned low-moderate bleeding-risk procedure will be randomized to one of five equally spaced platelet thresholds (less than 10 x 109/L, less than 20 x 109/L, less than 30 x 109/L, less than 40 x 109/L, less than 50 X 109/L) below which they will receive prophylactic platelet transfusions before any low-moderate bleeding-risk procedure occurring during the ICU episode up to ICU day 90. Once randomized, the clinical team will administer a platelet transfusion according to the assigned threshold and the most recent platelet count at the time of the planned procedure.	Other: 1- Platelet less than 10 x 109/L; Once randomized, the participant will receive a platelet transfusion if their most recent platelet count is less than 10 x 109/L at the time of the planned procedure.; Other: 2- Platelet less than 20 x 109/L; Once randomized, the participant will receive a platelet transfusion if their most recent platelet count is less than 20 x 109/L at the time of the planned procedure.; Other: 3- Platelet less than 30 x 109/L; Once randomized, the participant will receive a platelet transfusion if their most recent platelet count is less than 30 x 109/L at the time of the planned procedure.; Other: 4- Platelet less than 40 x 109/L; Once randomized, the participant will receive a platelet transfusion if their most recent platelet count is less than 40 x 109/L at the time of the planned procedure.; Other: 5- Platelet less than 50 x 109/L; Once randomized, the participant will receive a platelet transfusion if their most recent platelet count is less than 50 x 109/L at the time of the planned procedure.
Other: Nutrition; The intervention is bolus feeding (given 3 times a day to meet nutritional targets) with formula type left to the discretion of the precribing team. With 2 hours between eacn "feed". The control is continuous feeding (over 24-hour period) with formula type left to the discretion of the prescribing team, which is the current standard of care.	Other: Enteral nutrition - Boluses; Given 3 times a day.; Other: Enteral nutrition - Continuous; Given over 24-hour period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vasopressor Domain - Composite endpoint	Incorporate mortality, persistent organ dysfunction (POD) in the intensive care unit (ICU), days in hospital, and disposition at hospital discharge.	At hospital discharge up to day 30
Platelet Domain - All cause mortality	90-day all-cause mortality	90 days
Nutrition Domain - Recruitment rate	Recruitment rate of 2 patients per site per month.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet Domain - Mortality at discharge from hospital		Discharge from hospital
Platelet Domain - Mortality at 1 year		1 year after randomization
Platelet Domain - Bleeding outcomes in hospital (major and fatal bleeds)		During hospitalization
Platelet Domain - Transfusion complications	Transfusion-associated circulatory overload, transfusion-related acute lung injury, infections, anaphylaxis	During hospitalization
Platelet Domain - Days alive and at home at day 90		90 days
Platelet Domain - Number of days without persistent organ dysfunction in the ICU		Up to day 90
Platelet Domain - Health-related quality of life	Evaluated using EQ-5D-5L questionnaire	90 days
Vasopressor, Platelet and Nutrition Domains - Mortality		At hospital discharge up to day 30
Vasopressor, Platelet and Nutrition Domains - Persistent organ dysfunction (POD) in the ICU	POD is defined by the use of vasopressors, invasive mechanical ventilation, or new renal-replacement therapy whilst in ICU.	At hospital discharge up to day 30
Vasopressor, Platelet and Nutrition Domains - Number of days without POD in the ICU	POD is defined by the use of vasopressors, invasive mechanical ventilation, or new renal-replacement therapy whilst in ICU.	Up to day 30
Vasopressor, Platelet and Nutrition Domains - Disposition at hospital discharge	Increased level of care as indicated by change of address vs. return to baseline [previous home address]	At hospital discharge up to day 30
Vasopressor, Platelet and Nutrition Domains - Number of days without POD in the ICU	POD is defined by the use of vasopressors, invasive mechanical ventilation, or new renal-replacement therapy whilst in ICU.	At hospital discharge up to day 30
Nutrition Domain - Diarrhea	Defined by the World Health Organization (WHO) definition (3 or greater liquids stools/24 hours)	24 hours
Nutition Domain - Percentage of target nutritional intake	>80%	Over the course of the ICU stay up to day 30
Nutrition Domain - Vomiting	Vomiting 2 or more times in a 24-hour period	During ICU stay up to day 30

Collaborators and Investigators

• Sponsor: Université de Sherbrooke
• Investigators: Principal Investigator: Francois Lamontagne, MD, MSc, Université de Sherbrooke; Principal Investigator: Neill Adhikari, MDCM, MSc, Sunnybrook Research Institute

Publications and helpful links

Helpful Links

• Website of the CEPEC trial

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): June 30, 2030

Study Registration Dates

• First Submitted: September 10, 2024
• First Submitted That Met QC Criteria: September 17, 2024
• First Posted (Actual): September 20, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: ICU; Platelet; Vasopressor; Enteral nutrition; Adaptive platform trial
• Additional Relevant MeSH Terms: Vasoconstrictor Agents
• Other Study ID Numbers: MP-31-2025-5600

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No