Age of Blood in Children in Pediatric Intensive Care Units

Study Overview
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Brief Summary
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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).

Official Title
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Age of Blood in Children in Pediatric Intensive Care Units

Conditions
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Anemia

Intervention / Treatment
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* Biological: Short storage RBC age


Participation Criteria
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Eligibility Criteria
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Patients are considered eligible to participate in the trial if one of the following occur: First RBC transfusion is requested within the first 7 days (168 hours) of ICU admission. OR 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 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

Ages Eligible for Study
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Minimum Age: 3 Days
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Short storage<br>Red blood cells storage duration of equal to or less than 7 days. | Biological: Short storage RBC age<br>* IND obtained to cover the expiration date on the red blood cell unit<br>|
| Active Comparator: Standard issue<br>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<br>* IND obtained to cover the expiration date on the red blood cell unit<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Red blood cell transfusions, Red blood cell storage age, Pediatrics, Critical Care