Canadian Critical Care Comparative Effectiveness Platform

Official title

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

Overview

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.

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).

Interventions

• 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 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 Enteral nutrition - Boluses
  Given 3 times a day.

Primary outcome measures

• Vasopressor Domain - Composite endpoint [Time frame: At hospital discharge up to day 30]
• Platelet Domain - All cause mortality [Time frame: 90 days]
• Nutrition Domain - Recruitment rate [Time frame: 1 year]

Secondary outcome measures (12)

• Vasopressor, Platelet and Nutrition Domains - Mortality [Time frame: At hospital discharge up to day 30]
• Vasopressor, Platelet and Nutrition Domains - Persistent organ dysfunction (POD) in the ICU [Time frame: At hospital discharge up to day 30]
• Vasopressor, Platelet and Nutrition Domains - Number of days without POD in the ICU [Time frame: Up to day 30]
• Vasopressor, Platelet and Nutrition Domains - Disposition at hospital discharge [Time frame: At hospital discharge up to day 30]
• Vasopressor, Platelet and Nutrition Domains - Number of days without POD in the ICU [Time frame: At hospital discharge up to day 30]
• Platelet Domain - Mortality at discharge from hospital [Time frame: Discharge from hospital]
• Platelet Domain - Mortality at 1 year [Time frame: 1 year after randomization]
• Platelet Domain - Bleeding outcomes in hospital (major and fatal bleeds) [Time frame: During hospitalization]
• Platelet Domain - Transfusion complications [Time frame: During hospitalization]
• Platelet Domain - Days alive and at home at day 90 [Time frame: 90 days]
• Platelet Domain - Number of days without persistent organ dysfunction in the ICU [Time frame: Up to day 90]
• Platelet Domain - Health-related quality of life [Time frame: 90 days]

Eligibility criteria

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

Inclusion criteria

• Ongoing vasopressor infusion to treat hypotension, or would be used to treat clinician-defined hypotension as part of usual care;
• MAP <75 mmHg at any point;
• Patient expected to be in the ICU for >24 hours.

Exclusion criteria

• Treating team does not have equipoise for at least two contiguous MAP target ranges in the CEPEC Vasopressor Domain;
• Acute traumatic brain injury (within 7 days or ongoing active treatment for elevated intracranial pressure);
• Acute subarachnoid hemorrhage (within 21 days);
• Acute spinal cord injury (within 7 days of injury or ongoing vasopressor therapy for suspected spinal cord ischemia);
• Lung, heart, liver, kidney transplant recipient (within 7 days);
• Patient expected to become an organ donor (Donor Neurologic Death - DND or Donation After Circulatory Death - DCD);
• More than 24 hours since meeting inclusion criteria in the ICU;
• Previously randomized into the CEPEC Vasopressor Domain or a confounding trial.

PLATELET DOMAIN

Inclusion criteria

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

Exclusion criteria

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

NUTRITION DOMAIN

Inclusion criteria

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

Exclusion criteria

• Patients who have had gastrointestinal (GI) surgery; in the last 3 months and deemed not ready to receive possible bolus nutrition;
• Bowel obstruction or ischemia; active;
• Has a post-pyloric small bowel feeding tube;
• Active GI bleeding;
• Patient who is chronically receiving enteral nutrition.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Canada · 7 centers

• Hamilton Health Sciences - Juravinski Hospital — Hamilton
• The Ottawa Hospital — Ottawa
• Scarborough Health Network — Scarborough Village
• Niagara Health — St. Catharines
• Sunnybrook Health Sciences Centre — Toronto
• Centre hospitalier de l'Université de Montréal (CHUM) — Montreal
• CIUSSS de l'Estrie - CHUS — Sherbrooke

New Zealand · 1 center

• Auckland City Hospital — Auckland

United Kingdom · 1 center

• Intensive Care National Audit and Research Centre (coordinating centre for sites in UK. Si — London

Identifiers

NCT: NCT06605144 · MP-31-2025-5600

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗