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

NCT05405426 | Active Not Recruiting DMC

• 1 other identifier: W81XWH-22-1-0301
• Study Type: interventional
• Target: 228
• Locations: 3 countries
• Sites: 22

Brief Summary

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

Keywords

pediatric; children; ECMO; transfusion; neurodevelopment; TITRE

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  One year post-randomization (+/-2 mo)

Secondary Outcomes (26)

• Mixed venous oxygen saturation

  Daily AM (6 AM - 12 AM), during ECMO (up to 30 days post-randomization, whichever is earlier)

• Total volume of blood products administered

  30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient)

• Presence vs. absence of hospital-acquired Infection

  30 days post-randomization (up to time of ECMO decannulation if earlier; varies according to patient)

• Daily renal function

  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

  30 days post-randomization (up to time of ECMO decannulation if earlier; varies according to patient)

Study Arms (2)

Indication-based red blood cell transfusion strategy

ACTIVE COMPARATOR

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

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

OTHER

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

Interventions

Red blood cell transfusion 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; Indication-based red blood cell transfusion strategy

Eligibility Criteria

• Age: 0 Days - 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age \< 6 year at ECMO cannulation
• Veno-arterial (VA) mode of ECMO
• First ECMO run during the index hospitalization

You may not qualify if:

• 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 \> 18 hours after ECMO cannulation
• 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
• Limitation of care in place or being discussed
• Congenital bleeding disorders
• Hemoglobinopathies
• Primary Residence outside country of enrollment
• Lack of access to medical records required for calculation of pre-ECMO pSOFA score due to cannulation for ECMO at a non-trial center.
• Randomization not possible within 36 h following ECMO cannulation (e.g., due to staffing or delays related to communication with participant family)
• Planned transition to ventricular assist device (VAD) within 48 hours of commencing ECMO.
• 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).

Sponsors & Collaborators

• Boston Children's Hospital: lead

Study Sites (22)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Lucile Packard Children's Hospital

Palo Alto, California, 94304, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Lurie Children's Hospital

Chicago, Illinois, 60611, United States

Location

Riley Children's Hospital

Indianapolis, Indiana, 46202, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Michigan Medical Center

Ann Arbor, Michigan, 48109, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

MUSC Shawn Jenkins Children's Hospital

Charleston, South Carolina, 29425, United States

Location

Monroe Carell Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, 37232, United States

Location

Children's Health Dallas University of Texas Southwestern

Dallas, Texas, 75235, United States

Location

Texas Children's Hospital - Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84132, United States

Location

Inova Children's Hospital

Falls Church, Virginia, 22042, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

The Children's Hospital at Westmead

Westmead, New South Wales, Australia

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

MeSH Terms

Conditions

Multiple Organ Failure

Interventions

Erythrocyte Transfusion

Condition Hierarchy (Ancestors)

Shock; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Blood Component Transfusion; Blood Transfusion; Biological Therapy; Therapeutics

Study Officials

• Lynn A. Sleeper, ScD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor/Division of Cardiovascular Critical Care, Dept. of Cardiology

Model Details: 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

Study Record Dates

• First Submitted: May 2, 2022
• First Posted: June 6, 2022
• Study Start: April 14, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: October 21, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (20); CA (1); AU (1)