Trial of Indication-Based Transfusion of Red Blood Cells in ECMO (TITRE)

Boston Children's Hospital

Status: Active, not recruiting

Conditions: Red Blood Cell Transfusion; Organ Failure, Multiple; Extracorporeal Membrane Oxygenation

Treatments: Other: Red blood cell transfusion

Study type: Interventional

Funder types: Other

Identifiers

NCT05405426

W81XWH-22-1-0301

Details and patient eligibility

About

TITRE - Trial of Indication-based Transfusion of Red Blood Cells in ECMO, is a multicenter, prospective, randomized clinical trial. The overarching goal of TITRE is to determine whether restricting red blood cell (RBC) transfusion according to an indication-based strategy for those with bleeding and/or deficit of tissue oxygen delivery, compared with transfusion based on center-specific hemoglobin or hematocrit thresholds, can reduce organ dysfunction and improve later neurodevelopment in critically ill children receiving Extracorporeal Membrane Oxygenation (ECMO) support.

Full description

Observational studies of children on ECMO have shown an association between large-volume RBC transfusion and mortality. However, the hematocrit (or hemoglobin) level at which optimal tissue oxygen delivery occurs is unknown. TITRE - Trial of Indication-based Transfusion of Red Blood Cells in ECMO, is a prospective, randomized clinical trial to be conducted at 18-20 study sites. The overarching goal of TITRE is to determine whether restricting RBC transfusion according to an indication-based strategy for those with bleeding and/or deficit of tissue oxygen delivery, compared with transfusion based on center-specific hemoglobin or hematocrit thresholds, can reduce organ dysfunction and improve later neurodevelopment in critically ill children receiving ECMO support.

Aim 1: To test whether children < 6 years of age on ECMO support who are randomized to a strategy of indication-based versus center-specific threshold-based RBC transfusion will have greater improvement in organ function.

Aim 2: To test whether survivors among children age < 6 years on ECMO support who are randomized to indication-based compared to center-specific threshold-based RBC transfusion will have better neurodevelopmental outcomes and health-related QOL at one year post-randomization.

Key design features include: Randomization stratified by patient age (neonate:

=< 28d vs. non-neonate) and by diagnosis (CHD vs. other diagnosis); and a target sample size of 228 patients. Endpoints will be evaluated during ECMO, at hospital discharge, and at 3, 6, 9, and 12 months. To ensure trial integrity, the primary outcome (pSOFA: Pediatric Sequential Organ Failure Assessment score) will be adjudicated by an independent committee and neurodevelopmental assessments will be blinded.

Enrollment: 228 estimated patients

Sex: All

Ages: Under 6 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age < 6 year at ECMO cannulation
2. Veno-arterial (VA) mode of ECMO
3. First ECMO run during the index hospitalization

Exclusion criteria

1. Gestationally-corrected age < 37 weeks at the time of ECMO cannulation
2. Veno-venous (VV) mode of ECMO
3. Patients initially started on VV-ECMO and then transitioned to VA ECMO > 18 hours after ECMO cannulation
4. ECMO used for procedural support (ECMO deployed and decannulated in procedural area with no ICU ECMO care) or ECMO duration expected to be < 24 h
5. Limitation of care in place or being discussed
6. Congenital bleeding disorders
7. Hemoglobinopathies
8. Primary Residence outside country of enrollment
9. Concurrent participation in a separate interventional trial that has potential to impact neurodevelopment status of patient. (note that observational non-interventional studies do not qualify the patient for exclusion). This includes a patient already enrolled in TITRE
10. Lack of access to medical records required for calculation of pre-ECMO pSOFA score due to cannulation for ECMO at a non-trial center.
11. Randomization not possible within 36 h following ECMO cannulation (e.g., due to staffing or delays related to communication with participant family)
12. Planned transition to ventricular assist device (VAD) within 48 hours of commencing ECMO.
13. Clinically documented indication for a Red Blood Cell transfusion threshold that differs from the center-specific transfusion threshold (e.g., oncological treatment that limits donor exposure).

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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228 participants in 2 patient groups

Indication-based red blood cell transfusion strategy

Active Comparator group

Description:

Red blood cell transfusion will occur if the center-specific hemoglobin/hematocrit threshold for transfusion is met AND at least one of the following conditions is present: a) moderate or severe bleeding; b) reduced tissue oxygen delivery, defined as serum lactate \>5 mmol/L or 2 serum lactate levels \> 3 mmol/L measured 2 hours apart; or c) hemoglobin \< 8 g/dL or hematocrit \< 25%, except for neonates (age =\< 28 d) and children with single ventricle congenital heart disease (age \< 1 y) RBC transfusion for hemoglobin \< 10g/dL or hematocrit \<30% is allowed.

Treatment:

Other: Red blood cell transfusion

Center-specific hemoglobin/hematocrit threshold-based red blood cell transfusion strategy

Other group

Description:

Red blood cell transfusion will occur according to each study center's standard of care strategy, typically based on a particular hemoglobin threshold or hematocrit threshold. When hemoglobin or hematocrit decrease to the threshold, red blood cell transfusion is administered.

Treatment:

Other: Red blood cell transfusion