Clinical trial NCT05405426: Trial of Indication-Based Transfusion of Red Blood Cells in ECMO
Official title: TITRE: Trial of Indication-Based Transfusion of Red Blood Cells in ECMO
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Extracorporeal Membrane Oxygenation
Red Blood Cell Transfusion
Organ Failure, Multiple
Keywords: pediatric
children
ECMO
transfusion
neurodevelopment
TITRE
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
First posted: 2022-06-06
Enrollment: 228
Sex: ALL
Minimum age (years): 0
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Baseline-adjusted change in pSOFA (pediatric Sequential Organ Failure Assessment) score
timeFrame: At randomization and at 30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient)
measure: Bayley Infant Scales of Development, 4th edition (Bayley-4)
timeFrame: One year post-randomization (+/- 2 mo)
measure: Wechsler Preschool and Primary Scale of Intelligence (WPPSI - IV)
timeFrame: One year post-randomization (+/-2 mo)
Secondary outcomes:
measure: Mixed venous oxygen saturation
timeFrame: Daily AM (6 AM - 12 AM), during ECMO (up to 30 days post-randomization, whichever is earlier)
measure: Total volume of blood products administered
timeFrame: 30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient)
measure: Presence vs. absence of hospital-acquired Infection
timeFrame: 30 days post-randomization (up to time of ECMO decannulation if earlier; varies according to patient)
measure: Daily renal function
timeFrame: Daily up to 30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient)
measure: Acute kidney injury > stage 2
timeFrame: 30 days post-randomization (up to time of ECMO decannulation if earlier; varies according to patient)
measure: Number of ECMO circuit component replacements
timeFrame: At 30 days post-randomization
measure: Presence vs. absence of hemolysis
timeFrame: Daily up to 30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient)
measure: All-cause mortality
timeFrame: 30 days, in-hospital, and 1 year post-randomization
measure: Discharge location
timeFrame: At time of hospital discharge (assessed up to 1 year)
measure: Adaptive Behavior Assessment System-3 (ABAS-3)
timeFrame: 1 year post-randomization (+/- 2 mo)
measure: Child Behavior Checklist (CBCL)
timeFrame: 1 year post-randomization (+/- 2 mo)
measure: Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0)
timeFrame: 9 months post-randomization (+/- 1 mo)
measure: Pediatric Quality of Life Inventory Cardiac Module
timeFrame: 9 months post-randomization (+/- 1 mo)
measure: Number of Donor Exposures
timeFrame: Daily up to 30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient)
measure: Recannulation for ECMO < 48 hours and < 72 hours after decannulation
timeFrame: From ECMO decannulation hour to 72 hours following ECMO decannulation
measure: ECMO duration
timeFrame: During Hospitalization: From ECMO cannulation to ECMO decannulation, death, transition to Ventricular Assist Device (VAD) or 365 days post-randomization, whichever is earliest
measure: Duration of mechanical ventilation post-randomization
timeFrame: During Hospitalization: From Randomization to Extubation from Mechanical Ventilation, death, hospital discharge, or 365 days post-randomization, whichever is earliest
measure: Occurrence of Seizures
timeFrame: Randomization to Hospital Discharge or 90 days post-randomization, whichever is earliest
measure: Stroke or Intracranial Hemorrhage during ECMO
timeFrame: Time of ECMO cannulation to ECMO decannulation, death or 30 days post-randomization, whichever occurs first
measure: Stroke or Intracranial Hemorrhage prior to Hospital Discharge
timeFrame: ECMO cannulation to 90 days post-randomization or hospital discharge, whichever occurs first
measure: Pediatric Overall Performance Category (POPC)
timeFrame: Randomization to study completion (completion of 12 month neurodevelopment assessment)
measure: Functional Status Score (FSS)
timeFrame: Randomization to study completion (completion of 12 month neurodevelopment assessment)
measure: ICU Length of Stay among survivors during index hospitalization
timeFrame: ICU Admission to ICU discharge, death or 365 post-randomization, whichever occurs first
measure: Hospital length of stay among survivors during index hospitalization
timeFrame: Hospital Admission to discharge death, or 365 days post-randomization, whichever occurs first
measure: Pediatric Cerebral Performance Category (PCPC)
timeFrame: Randomization to study completion (completion of 12 month neurodevelopment assessment)
measure: Number of ICU admissions prior to discharge from index hospitalization among survivors
timeFrame: Index ICU discharge to Hospital discharge or 365 days post-randomization, whichever occurs first
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Chicago
country: United States
facility: Lurie Children's Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Riley Children's Hospital
state: Indiana
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Charleston
country: United States
facility: MUSC Shawn Jenkins Children's Hospital
state: South Carolina
city: Nashville
country: United States
facility: Monroe Carell Jr. Children's Hospital at Vanderbilt
state: Tennessee
city: Dallas
country: United States
facility: Children's Health Dallas University of Texas Southwestern
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital - Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Falls Church
country: United States
facility: Inova Children's Hospital
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Westmead
country: Australia
facility: The Children's Hospital at Westmead
state: New South Wales
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: Boston Children's Hospital
name: Lynn A. Sleeper, ScD
role: PRINCIPAL_INVESTIGATOR
References: