Trial of Indication-Based Transfusion of Red Blood Cells in ECMO
Purpose
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.
Conditions
- Extracorporeal Membrane Oxygenation
- Red Blood Cell Transfusion
- Organ Failure, Multiple
Eligibility
- Eligible Ages
- Between 1 Day and 6 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Age < 6 year at ECMO cannulation 2. Veno-arterial (VA) mode of ECMO 3. First ECMO run during the index hospitalization
Exclusion Criteria
- 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 4. ECMO used for procedural support (ECMO deployed and decannulated in procedural area with no ICU ECMO care) 5. ECMO duration expected to be < 24 h 6. Limitation of care or withdrawal of support discussed or in place after ECMO deployment 7. Congenital bleeding disorders 8. Hemoglobinopathies 9. Primary Residence outside country of enrollment 10. Concurrent participation in a separate interventional trial that has potential to impact neurodevelopment status of patient 11. 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 12. Randomization not possible within 36 h following ECMO cannulation (e.g., due to staffing or delays related to communication with participant family 13. ECMO deployed as a bridge to ventricular assist device
Study Design
- Phase
- N/A
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Two independent study arms will be used: indication-based red blood cell transfusion strategy vs. a center-specific standard of care hemoglobin/hematocrit threshold-based red blood cell transfusion strategy
- Primary Purpose
- Other
- Masking
- Single (Outcomes Assessor)
- Masking Description
- Adjudicators for the primary endpoint (organ failure assessment score) will be blinded to treatment assignment. Specialists for neurodevelopmental assessment of participants will be blinded to treatment assignment.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator Indication-based red blood cell transfusion strategy |
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. |
|
|
Other Center-specific hemoglobin/hematocrit threshold-based red blood cell transfusion strategy |
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. |
|
Recruiting Locations
Nashville, Tennessee 37232
More Details
- Status
- Recruiting
- Sponsor
- Boston Children's Hospital
Detailed 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.