Trial of Indication-Based Transfusion of Red Blood Cells in ECMO

NCT ID: NCT05405426

Last Updated: 2025-10-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

228 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-04-14

Study Completion Date

2026-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Extracorporeal Membrane Oxygenation Red Blood Cell Transfusion Organ Failure, Multiple

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

OTHER

Blinding Strategy

SINGLE

Outcome Assessors
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.

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Red blood cell transfusion

Intervention Type OTHER

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.

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.

Group Type OTHER

Red blood cell transfusion

Intervention Type OTHER

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.

Interventions

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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.

Intervention Type OTHER

Eligibility Criteria

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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).
Minimum Eligible Age

0 Days

Maximum Eligible Age

6 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Boston Children's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Ravi Thiagarajan

Professor/Division of Cardiovascular Critical Care, Dept. of Cardiology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Lynn A. Sleeper, ScD

Role: PRINCIPAL_INVESTIGATOR

Boston Children's Hospital

Locations

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Phoenix Children's Hospital

Phoenix, Arizona, United States

Site Status

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Lucile Packard Children's Hospital

Palo Alto, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Site Status

Lurie Children's Hospital

Chicago, Illinois, United States

Site Status

Riley Children's Hospital

Indianapolis, Indiana, United States

Site Status

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Site Status

Children's Hospital of Michigan

Detroit, Michigan, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

MUSC Shawn Jenkins Children's Hospital

Charleston, South Carolina, United States

Site Status

Monroe Carell Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, United States

Site Status

Children's Health Dallas University of Texas Southwestern

Dallas, Texas, United States

Site Status

Texas Children's Hospital - Baylor College of Medicine

Houston, Texas, United States

Site Status

Primary Children's Hospital

Salt Lake City, Utah, United States

Site Status

Inova Children's Hospital

Falls Church, Virginia, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

The Children's Hospital at Westmead

Westmead, New South Wales, Australia

Site Status

The Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Countries

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United States Australia Canada

Other Identifiers

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W81XWH-22-1-0301

Identifier Type: -

Identifier Source: org_study_id

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