An interventional study of Red blood cell transfusion in Extracorporeal Membrane Oxygenation, Red Blood Cell Transfusion and Organ Failure, Multiple, sponsored by Boston Children's Hospital. Active, not recruiting at 22 sites in 3 countries. Open to participants aged 0 Days to 6 Years. Per ClinicalTrials.gov, last updated 2026-07-02.
Sponsored by Boston Children's Hospital · Not applicable, Interventional, and Other
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.
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 22 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 240 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.
193 studies on the registry are indexed under Multiple Organ Failure; 47 are open to participants now.
This study's planned enrollment of 228 is above the median of 88 across 90 interventional studies indexed under Multiple Organ Failure.
Browse Multiple Organ Failure studies →Boston Children's Hospital is the lead sponsor of 608 studies on the registry; 147 are open to participants now.
Of its 32 completed or terminated interventional studies of FDA-regulated products, 19 (59%) have results posted.
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Exclusion Criteria:
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: Red blood cell transfusion
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.
Other: Red blood cell transfusion
The intervention is a strategy for when red blood cell transfusion will be administered (see description of Arms). However, volume of RBC transfused in the two arms is not specified by this study. Red blood cell transfusion strategy for ECMO weaning and decannulation is not specified by this study. Red blood cell transfusion after ECMO decannulation is not specified by this study.
Baseline-adjusted change in pSOFA (pediatric Sequential Organ Failure Assessment) score
The pSOFA score ranges from 0 (no organ dysfunction) through 24 (severe dysfunction in all 6 organs assessed). If death occurs during ECMO within 30 days, a score of 24 is assigned.
Time frame: At randomization and at 30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient)
Bayley Infant Scales of Development, 4th edition (Bayley-4)
Scales for Cognitive, Language (Expressive and Receptive), Motor (Gross and Fine), and Social-Emotional. For ages 16 days to 42 months. Composite score range is 40 to 160. Higher scores indicate better performance.
Time frame: One year post-randomization (+/- 2 mo)
Wechsler Preschool and Primary Scale of Intelligence (WPPSI - IV)
Index scores include Verbal Comprehension, Visual Spatial, Working Memory, and Full Scale Intelligence Quotient (IQ). Score range is 40 to 160. Higher scores indicate better performance.
Time frame: One year post-randomization (+/-2 mo)
Mixed venous oxygen saturation
Oxygen content of blood that returns to the heart after meeting tissue needs
Time frame: Daily AM (6 AM - 12 AM), during ECMO (up to 30 days post-randomization, whichever is earlier)
Total volume of blood products administered
Packed RBC and whole blood, cryoprecipitate, plasma, platelets
Time frame: 30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient)
Presence vs. absence of hospital-acquired blood stream Infection
Hospital-acquired blood stream infection that is not present or incubating at the time of admission to hospital
Time frame: 30 days post-randomization (up to time of ECMO decannulation if earlier; varies according to patient)
Daily renal function
Serum creatinine, blood urea nitrogen (BUN)
Time frame: Daily up to 30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient)
Acute kidney injury > stage 2
Kidney Disease Improving Global Outcomes (KDIGO) definition
Time frame: 30 days post-randomization (up to time of ECMO decannulation if earlier; varies according to patient)
Number of ECMO circuit component replacements
Replacement of oxygenator and/or pump
Time frame: At 30 days post-randomization
Presence vs. absence of hemolysis
According to plasma hemoglobin values
Time frame: Daily up to 30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient)
All-cause mortality
Death from any cause
Time frame: 30 days, in-hospital, and 1 year post-randomization
Discharge location
Home vs. rehabilitation facility
Time frame: At time of hospital discharge (assessed up to 1 year)
Adaptive Behavior Assessment System-3 (ABAS-3)
Composite scores for overall adaptive functioning (General Adaptive Composite, GAC), Conceptual, Social and Practical domains as well as nine subscales. Higher score indicates better behavior.
Time frame: 1 year post-randomization (+/- 2 mo)
Child Behavior Checklist (CBCL)
Parent-report; child minimum age 1.5 years. Higher score indicates worse behavior.
Time frame: 1 year post-randomization (+/- 2 mo)
Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0)
Parent-report; child minimum age 2.0 years. Higher score indicates better quality of life.
Time frame: 9 months post-randomization (+/- 1 mo)
Pediatric Quality of Life Inventory Cardiac Module
Parent-report; child minimum age 2.0 years. To be completed for participants with a congenital heart disease diagnosis. Higher score indicates better quality of life.
Time frame: 9 months post-randomization (+/- 1 mo)
Number of Donor Exposures
Number of Donor Exposures for RBC transfusion
Time frame: Daily up to 30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient)
Recannulation for ECMO < 48 hours and < 72 hours after decannulation
No: of patients recannulated for ECMO within 48 hours and 72 hours post-decannulation
Time frame: From ECMO decannulation hour to 72 hours following ECMO decannulation
ECMO duration
ECMO duration in hours: Time period from ECMO cannulation to first successful ECMO decannulation in hours. Time accrued during ECMO for additional ECMO runs (i.e. those cannulated within 36 hours following first decannulation) will be included as total ECMO duration
Time frame: During Hospitalization: From ECMO cannulation to ECMO decannulation, death, transition to Ventricular Assist Device (VAD) or 365 days post-randomization, whichever is earliest
Duration of mechanical ventilation post-randomization
Duration of mechanical ventilation post-randomization in hours: Randomization to first successful extubation from mechanical ventilation hours; for patients with tracheostomy that require mechanical ventilatory support at the time of ICU discharge: time of ICU discharge to compute mechanical ventilation duration.
Time frame: During Hospitalization: From Randomization to Extubation from Mechanical Ventilation, death, hospital discharge, or 365 days post-randomization, whichever is earliest
Occurrence of Seizures
Occurrence of electroencephalographic evidence of seizure prior to hospital discharge or within 90 d post randomization, whichever is earliest
Time frame: Randomization to Hospital Discharge or 90 days post-randomization, whichever is earliest
Stroke or Intracranial Hemorrhage during ECMO
Occurrence of brain infarction, intracranial hemorrhage, or ischemic injury during ECMO (composite) confirmed using head ultrasound and Computed Tomography (CT) during ECMO
Time frame: Time of ECMO cannulation to ECMO decannulation, death or 30 days post-randomization, whichever occurs first
Stroke or Intracranial Hemorrhage prior to Hospital Discharge
Proportion of patients with brain infarction, intracranial hemorrhage, or ischemic injury (composite) confirmed using head ultrasound, CT, or Magnetic Resonance Imaging (MRI) prior to hospital discharge or within 90 d post randomization, whichever is earliest
Time frame: ECMO cannulation to 90 days post-randomization or hospital discharge, whichever occurs first
Pediatric Overall Performance Category (POPC)
Pediatric Overall Performance (POPC; score range 0 to 6; Unit: categories on a scale; value: lower is better) at Hospital Discharge, 3, 6, 9, 12 months post-randomization.
Time frame: Randomization to study completion (completion of 12 month neurodevelopment assessment)
Functional Status Score (FSS)
Functional Status Score (FSS; score range 6 to 30; Unit: numerical value on a scale; lower is better) at hospital discharge, 3, 6, 9, 12 months post-randomization
Time frame: Randomization to study completion (completion of 12 month neurodevelopment assessment)
ICU Length of Stay among survivors during index hospitalization
Duration of hospitalization in the ICU among survivors in days during index hospitalization. For ICU readmissions only the only days in the first 2 ICU readmissions will be included
Time frame: ICU Admission to ICU discharge, death or 365 post-randomization, whichever occurs first
Hospital length of stay among survivors during index hospitalization
Duration of hospitalization among survivors in days during index hospitalization
Time frame: Hospital Admission to discharge death, or 365 days post-randomization, whichever occurs first
Pediatric Cerebral Performance Category (PCPC)
Pediatric Cerebral Performance Category (POPC; score range 0 to 6; Unit: categories on a scale, lower is better) at Hospital Discharge, 3, 6, 9, 12 months post-randomization.
Time frame: Randomization to study completion (completion of 12 month neurodevelopment assessment)
Number of ICU admissions prior to discharge from index hospitalization among survivors
Number of ICU admissions during index hospitalization. ICU admissions are defined as number of ICU admissions following discharge from the first ICU admission.
Time frame: Index ICU discharge to Hospital discharge or 365 days post-randomization, whichever occurs first
Proportion of ECMO days meeting moderate - severe bleeding criteria
Number of days meeting criteria for moderate or severe bleeding during ECMO
Time frame: Daily up to 30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient)
Plan to share: No
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Started Apr 2023 (actual). Primary completion is estimated for Oct 2026, 42 months after the start.
Of 28 interventional studies with no phase under Multiple Organ Failure, half reached primary completion within 24 months of starting (the median), counting those still running; a quarter within 12 and three quarters within 54. This study's planned 42 months is above that.
How these figures are worked out, and which studies are left out of them.
This study is active, not recruiting, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
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