Overview
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.
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.
Eligibility
Inclusion Criteria:
- Age < 6 year at ECMO cannulation
- Veno-arterial (VA) mode of ECMO
- First ECMO run during the index hospitalization
Exclusion Criteria:
- Gestationally-corrected age < 37 weeks at the time of ECMO cannulation
- Veno-venous (VV) mode of ECMO
- Patients initially started on VV-ECMO and then transitioned to VA ECMO
- ECMO used for procedural support (ECMO deployed and decannulated in procedural area with no ICU ECMO care)
- ECMO duration expected to be < 24 h
- Limitation of care or withdrawal of support discussed or in place after ECMO deployment
- Congenital bleeding disorders
- Hemoglobinopathies
- Primary Residence outside country of enrollment
- Concurrent participation in a separate interventional trial that has potential to impact neurodevelopment status of patient
- Patients cannulated for ECMO at a non-trial center and transferred to a trial site. An exception: those cannulated for ECMO at another non-trial site location that is part of the same healthcare system and subsequently transferred to a trial site will be eligible
- Randomization not possible within 36 h following ECMO cannulation (e.g., due to staffing or delays related to communication with participant family
- ECMO deployed as a bridge to ventricular assist device