Age of Blood in Children in Pediatric Intensive Care Units (ABC-PICU)

ABC PICU is a randomized clinical trial that will compare the clinical consequences of RBC storage duration in 1538 critically ill children. Laboratory and observational evidence points to serious concerns about the lack of safety and effectiveness of older RBCs, especially in more vulnerable populations. Physicians and institutions have been systematically transfusing fresh RBCs to some pediatric patients primarily because of beliefs that the use of fresh RBCs improve outcomes. Conversely, the standard practice of blood banks is to deliver the oldest RBC unit in order to decrease blood wastage. To provide much needed high quality evidence to answer the question "do RBCs of reduced storage duration improve outcomes?" The ABC PICU Trial will conduct a RCT comparing development of New or Progressive Multiple Organ Dysfunction Syndrome (NPMODS) in critically ill children transfused with either RBCs stored ≤ 7 days or standard issue RBCs (expected mean RBC storage duration of 17-21 days).

Study Overview

• Status: Completed
• Conditions: Anemia
• Intervention / Treatment: Biological: Short storage RBC age

• Study Type: Interventional
• Enrollment (Actual): 1538
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G2
    • Centre Hospitalier de I'Universite Laval
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Stollery Children's Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 6R8
      • IWK Health Centre
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • CHU Sainte Justine
• France
  • Bordeaux, France, 33076
    • Place Amélie Raba Léon
  • Lille, France, 59037
    • Hôpital Jeanne de Flandre
  • Nantes, France, 44093
    • Hopital Mère Enfant
  • Paris, France, 75019
    • Hôpital Robert Debré
  • Paris, France, 75743
    • Hôpital Universitaire Necker - Enfants Malades
  • Rennes, France, 35033
    • CHU Pontchaillou
  • Malades Paris
    • Paris, Malades Paris, France, 75015
      • Hôpital Necker-enfants
• Israel
  • Tel HaShomer, Israel
    • Sheba Medical Center
• Italy
  • Florence, Italy
    • Meyer's Hospital
  • Rome, Italy, 00165
    • Bamino Gesú
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35223
      • University of Alabama at Birmingham
  • Arizona
    • Tucson, Arizona, United States, 85721
      • Diamond Children's Medical Center
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
  • Colorado
    • Aurora, Colorado, United States, 80045
      • The Children's Hospital and University of Colorado Denver School of Medicine
  • Florida
    • Gainesville, Florida, United States
      • UF Health Shands Children's Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
    • Park Ridge, Illinois, United States
      • Lutheran General Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • James Whitcomb Riley Hospital for Children
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
    • Rochester, New York, United States, 14642
      • Golisano Children's Hospital at Strong
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
  • Texas
    • Dallas, Texas, United States, 75390
      • Children's Medical Center Dallas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 days to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Patients are considered eligible to participate in the trial if one of the following occur:

1. First RBC transfusion is requested within the first 7 days (168 hours) of ICU admission.

   OR

2. First RBC transfusion is requested for a patient in the Emergency Room, and the PICU team is involved with the clinical care of the patient, and the patient will definitively be transferred to the ICU.

   OR

3. Patient assessed pre-operatively and for whom ICU admission is planned post-operatively, and who is determined to definitively require a first RBC transfusion during surgery.

Inclusion Criteria:

Eligible critically ill pediatric patients who have an expected length of stay after transfusion in the ICU > 24 hours based on the best judgment of the attending ICU staff.

Exclusion Criteria:

• Age at time of enrollment < 3 days from birth or has reached their 16th birthday.
• Post-conception age < 36 weeks at time of enrollment
• Documented RBC transfusion within the 28 days prior to fulfilling the eligibility criteria
• Previously randomized in this study
• Weight < 3.0 kg on ICU admission
• Known Pregnancy
• Conscious objection or unwillingness to receive blood products
• Not expected to survive beyond 24 hours, brain death or suspected brain death
• Limitation or withdrawal of care decisions have been made
• Enrollment in another randomized clinical trial which has not been approved for co-enrollment
• Patients for whom autologous and/or directed donation RBCs will be provided
• Patients for whom the treating physician routinely and systematically requests RBC ≤ 14 days of storage
• Patients for whom there systematically exist RBC aliquoting policies that mandate the initial use of units stored ≤ 14 days (ex: Pedi-Pack).
• On ECMO or plan to be immediately placed on ECMO at time of enrollment
• Patient predicted or presumed to require a massive transfusion (> 40ml/kg of all blood components in a 24 hour period) according to treating physician judgment
• Refusal by physician
• Inability to obtain consent
• Blood bank personnel experiences difficulties in securing blood products (difficult cross matches, rare blood groups and diseases like IgA deficiency)
• Insufficient number of ABO type compatible RBC units available in the blood bank at randomization with a storage time ≤ 7 days (minimum 1 unit regardless of patient age)
• All RBC units available for the patient are not leukocyte-reduced prior to storage

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Short storage; Red blood cells storage duration of equal to or less than 7 days.	Biological: Short storage RBC age; IND obtained to cover the expiration date on the red blood cell unit
Active Comparator: Standard issue; Red blood cells storage duration of 2 to 42 days with an expected average length of storage of about 17-21 days.	Biological: Short storage RBC age; IND obtained to cover the expiration date on the red blood cell unit

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With New or Progressive Multiple Organ Dysfunction Syndrome (NPMODS)	The primary outcome measure of this RCT is NPMODS defined as the proportion of patients who die during the 28 days after randomization or who develop NPMODS. For patients with no organ dysfunction at randomization, New MODS is the development of ≥ 2 concurrent organ dysfunctions during the 28 days after randomization. For patients with 1 organ dysfunction at randomization, New MODS is the development of at least 1 other concurrent organ dysfunction after randomization. Patients with MODS (ie concurrent dysfunction of ≥ 2 organ systems) at randomization can develop Progressive MODS defined as development of at least 1 additional concurrent organ dysfunction at during the 28 days after randomization. All deaths will be considered Progressive MODS. NPMODS will be monitored up to 28 days or ICU discharge because it is almost never observed beyond this time in children.	28 days after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Organ Dysfunction	Difference in number of organ dysfunctions.	Up to 28 days after randomization.
PELOD-2 Score	Difference in PELOD-2 score. Change from randomization to Worst PELOD-2 score. (Pediatric Logistic Organ Dysfunction) Points are on a range of 0-6 and based on Neurologic, cardiovascular, renal, respiratory, and hematologic function. The higher the score the worse the organ failure is and higher mortality rate.	Up to 28 days after randomization.
Nosocomial Infection	Difference in nosocomial infection rate.	Up to 28 days after randomization.
Sepsis, Severe Sepsis, Septic Shock	Difference in the rate of sepsis, severe sepsis or septic shock.	Up to 28 days after randomization.
Acute Respiratory Distress Syndrome	Difference in the rate of acute respiratory distress syndrome.	Up to 28 days after randomization.
Mechanical Ventilation	28 day mechanical ventilation free days	Up to 28 days after randomization.
ICU Free Days	Difference in ICU free days.	Up to 28 days after randomization
Mortality	Difference in 90 day mortality.	Up to 90 days after randomization
Delirium	Transfusion Associated Delirium in pediatric critically ill children	up to 72 hours post last study transfusion

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Canadian Institutes of Health Research (CIHR); Ministere de la Sante et des Services Sociaux
• Investigators: Principal Investigator: Philip C. Spinella, MD, Washington University School of Medicine, St. Louis; Principal Investigator: Marisa Tucci, MD, Ste-Justine Hospital, Montreal

Publications and helpful links

General Publications

• Spinella PC, Tucci M, Fergusson DA, Lacroix J, Hebert PC, Leteurtre S, Schechtman KB, Doctor A, Berg RA, Bockelmann T, Caro JJ, Chiusolo F, Clayton L, Cholette JM, Guerra GG, Josephson CD, Menon K, Muszynski JA, Nellis ME, Sarpal A, Schafer S, Steiner ME, Turgeon AF; ABC-PICU Investigators, the Canadian Critical Care Trials Group, the Pediatric Acute Lung Injury and Sepsis Investigators Network, the BloodNet Pediatric Critical Care Blood Research Network, and the Groupe Francophone de Reanimation et Urgences P. Effect of Fresh vs Standard-issue Red Blood Cell Transfusions on Multiple Organ Dysfunction Syndrome in Critically Ill Pediatric Patients: A Randomized Clinical Trial. JAMA. 2019 Dec 10;322(22):2179-2190. doi: 10.1001/jama.2019.17478.
• Tucci M, Lacroix J, Fergusson D, Doctor A, Hebert P, Berg RA, Caro J, Josephson CD, Leteurtre S, Menon K, Schechtman K, Steiner ME, Turgeon AF, Clayton L, Bockelmann T, Spinella PC; Canadian Critical Care Trials Group; Pediatric Critical Care Blood Research Network (BloodNet); Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. The age of blood in pediatric intensive care units (ABC PICU): study protocol for a randomized controlled trial. Trials. 2018 Jul 28;19(1):404. doi: 10.1186/s13063-018-2809-y.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: August 9, 2013
• First Submitted That Met QC Criteria: October 30, 2013
• First Posted (Estimate): November 6, 2013

Study Record Updates

• Last Update Posted (Actual): April 29, 2021
• Last Update Submitted That Met QC Criteria: April 5, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Pediatrics; Critical Care; Red blood cell transfusions; Red blood cell storage age
• Other Study ID Numbers: 201302030; 1U01HL116383-01 (U.S. NIH Grant/Contract); MOP 126113 (Other Grant/Funding Number: Canadian Institutes of Health Research (CIHR))