Anemia
Conditions
Keywords
Red blood cell transfusions, Red blood cell storage age, Pediatrics, Critical Care
Brief summary
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).
Interventions
BIOLOGICALShort storage RBC age
IND obtained to cover the expiration date on the red blood cell unit
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Canadian Institutes of Health Research (CIHR)
Ministere de la Sante et des Services Sociaux
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
3 Days to 15 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With New or Progressive Multiple Organ Dysfunction Syndrome (NPMODS) | 28 days after randomization | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PELOD-2 Score | Up to 28 days after randomization. | 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. |
| Nosocomial Infection | Up to 28 days after randomization. | Difference in nosocomial infection rate. |
| Sepsis, Severe Sepsis, Septic Shock | Up to 28 days after randomization. | Difference in the rate of sepsis, severe sepsis or septic shock. |
| Acute Respiratory Distress Syndrome | Up to 28 days after randomization. | Difference in the rate of acute respiratory distress syndrome. |
| Organ Dysfunction | Up to 28 days after randomization. | Difference in number of organ dysfunctions. |
| ICU Free Days | Up to 28 days after randomization | Difference in ICU free days. |
| Mortality | Up to 90 days after randomization | Difference in 90 day mortality. |
| Delirium | up to 72 hours post last study transfusion | Transfusion Associated Delirium in pediatric critically ill children |
| Mechanical Ventilation | Up to 28 days after randomization. | 28 day mechanical ventilation free days |
Countries
Canada, France, Israel, Italy, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Short Storage Red blood cells storage duration of equal to or less than 7 days.
Short storage RBC age: IND obtained to cover the expiration date on the red blood cell unit | 728 |
| Standard Issue Red blood cells storage duration of 2 to 42 days with an expected average length of storage of about 17-21 days.
Short storage RBC age: IND obtained to cover the expiration date on the red blood cell unit | 733 |
| Total | 1,461 |
Baseline characteristics
| Characteristic | Short Storage | Standard Issue | Total |
|---|---|---|---|
| Age, Continuous | 1.8 year | 1.9 year | 1.8 year |
| Ethnicity (NIH/OMB) Hispanic or Latino | 68 Participants | 82 Participants | 150 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 515 Participants | 508 Participants | 1023 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 145 Participants | 143 Participants | 288 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 22 Participants | 11 Participants | 33 Participants |
| Race (NIH/OMB) Asian | 37 Participants | 29 Participants | 66 Participants |
| Race (NIH/OMB) Black or African American | 86 Participants | 103 Participants | 189 Participants |
| Race (NIH/OMB) More than one race | 24 Participants | 13 Participants | 37 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 5 Participants | 4 Participants | 9 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 155 Participants | 158 Participants | 313 Participants |
| Race (NIH/OMB) White | 399 Participants | 415 Participants | 814 Participants |
| Region of Enrollment Canada | 196 participants | 194 participants | 390 participants |
| Region of Enrollment France | 92 participants | 89 participants | 181 participants |
| Region of Enrollment Israel | 6 participants | 9 participants | 15 participants |
| Region of Enrollment Italy | 19 participants | 18 participants | 37 participants |
| Region of Enrollment United States | 415 participants | 423 participants | 838 participants |
| Sex: Female, Male Female | 352 Participants | 339 Participants | 691 Participants |
| Sex: Female, Male Male | 376 Participants | 394 Participants | 770 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 49 / 716 | 45 / 714 |
| other Total, other adverse events | 0 / 728 | 0 / 733 |
| serious Total, serious adverse events | 80 / 728 | 84 / 733 |
Outcome results
Primary
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.
Time frame: 28 days after randomization
Population: Development of organ dysfunction in all participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Short Storage | Number of Participants With New or Progressive Multiple Organ Dysfunction Syndrome (NPMODS) | 147 Participants |
| Standard Issue | Number of Participants With New or Progressive Multiple Organ Dysfunction Syndrome (NPMODS) | 133 Participants |
Secondary
Acute Respiratory Distress Syndrome
Difference in the rate of acute respiratory distress syndrome.
Time frame: Up to 28 days after randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Short Storage | Acute Respiratory Distress Syndrome | 41 Participants |
| Standard Issue | Acute Respiratory Distress Syndrome | 29 Participants |
Secondary
Delirium
Transfusion Associated Delirium in pediatric critically ill children
Time frame: up to 72 hours post last study transfusion
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Short Storage | Delirium | 55 Participants |
| Standard Issue | Delirium | 54 Participants |
Secondary
ICU Free Days
Difference in ICU free days.
Time frame: Up to 28 days after randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Short Storage | ICU Free Days | 21.9 days |
| Standard Issue | ICU Free Days | 22.0 days |
Secondary
Mechanical Ventilation
28 day mechanical ventilation free days
Time frame: Up to 28 days after randomization.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Short Storage | Mechanical Ventilation | 25.4 days |
| Standard Issue | Mechanical Ventilation | 25.8 days |
Secondary
Mortality
Difference in 90 day mortality.
Time frame: Up to 90 days after randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Short Storage | Mortality | 49 Participants |
| Standard Issue | Mortality | 45 Participants |
Secondary
Nosocomial Infection
Difference in nosocomial infection rate.
Time frame: Up to 28 days after randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Short Storage | Nosocomial Infection | 24 Participants |
| Standard Issue | Nosocomial Infection | 23 Participants |
Secondary
Organ Dysfunction
Difference in number of organ dysfunctions.
Time frame: Up to 28 days after randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Short Storage | Organ Dysfunction | 129 Participants |
| Standard Issue | Organ Dysfunction | 133 Participants |
Secondary
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.
Time frame: Up to 28 days after randomization.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Short Storage | PELOD-2 Score | 0.5 score on a scale | Standard Error 5.8 |
| Standard Issue | PELOD-2 Score | -0.05 score on a scale | Standard Error 4.7 |
Secondary
Sepsis, Severe Sepsis, Septic Shock
Difference in the rate of sepsis, severe sepsis or septic shock.
Time frame: Up to 28 days after randomization.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Short Storage | Sepsis, Severe Sepsis, Septic Shock | Sepsis | 160 Participants |
| Short Storage | Sepsis, Severe Sepsis, Septic Shock | Severe Sepsis | 63 Participants |
| Short Storage | Sepsis, Severe Sepsis, Septic Shock | Septic Shock | 59 Participants |
| Standard Issue | Sepsis, Severe Sepsis, Septic Shock | Sepsis | 154 Participants |
| Standard Issue | Sepsis, Severe Sepsis, Septic Shock | Severe Sepsis | 60 Participants |
| Standard Issue | Sepsis, Severe Sepsis, Septic Shock | Septic Shock | 57 Participants |