Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05405426
Other study ID # W81XWH-22-1-0301
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
Start date April 14, 2023
Est. completion date December 2025

Study information

Verified date May 2024
Source Boston Children's Hospital
Contact Ravi Thiagarajan, MBBS
Phone 617-355-4023
Email ravi.thiagarajan@cardio.chboston.org
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 228
Est. completion date December 2025
Est. primary completion date October 2024
Accepts healthy volunteers No
Gender All
Age group 1 Day to 6 Years
Eligibility 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 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


Related Conditions & MeSH terms


Intervention

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.

Locations

Country Name City State
Australia The Children's Hospital at Westmead Westmead New South Wales
Canada The Hospital for Sick Children Toronto Ontario
United States University of Michigan Medical Center Ann Arbor Michigan
United States Children's Healthcare of Atlanta Atlanta Georgia
United States Children's Hospital Colorado Aurora Colorado
United States Boston Children's Hospital Boston Massachusetts
United States MUSC Shawn Jenkins Children's Hospital Charleston South Carolina
United States Lurie Children's Hospital Chicago Illinois
United States Cincinnati Children's Hospital Medical Center Cincinnati Ohio
United States Children's Health Dallas University of Texas Southwestern Dallas Texas
United States Children's Hospital of Michigan Detroit Michigan
United States Inova Children's Hospital Falls Church Virginia
United States Texas Children's Hospital - Baylor College of Medicine Houston Texas
United States Riley Children's Hospital Indianapolis Indiana
United States Arkansas Children's Hospital Little Rock Arkansas
United States Children's Hospital Los Angeles Los Angeles California
United States Monroe Carell Jr. Children's Hospital at Vanderbilt Nashville Tennessee
United States Lucile Packard Children's Hospital Palo Alto California
United States Children's Hospital of Philadelphia Philadelphia Pennsylvania
United States Phoenix Children's Hospital Phoenix Arizona
United States Primary Children's Hospital Salt Lake City Utah
United States Seattle Children's Hospital Seattle Washington

Sponsors (1)

Lead Sponsor Collaborator
Boston Children's Hospital

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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)
Primary 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)
Primary 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 Mixed venous oxygen saturation Oxygen content of blood that returns to the heart after meeting tissue needs Daily AM (6 AM - 12 AM), during ECMO (up to 30 days post-randomization, whichever is earlier)
Secondary Total volume of blood products administered Packed RBC and whole blood, cryoprecipitate, plasma, platelets 30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient)
Secondary Presence vs. absence of hospital-acquired Infection Nosocomially-acquired infection that is not present or incubating at the time of admission to hospital 30 days post-randomization (up to time of ECMO decannulation if earlier; varies according to patient)
Secondary Daily renal function Serum creatinine, blood urea nitrogen (BUN) Daily up to 30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient)
Secondary Acute kidney injury > stage 2 Kidney Disease Improving Global Outcomes (KDIGO) definition 30 days post-randomization (up to time of ECMO decannulation if earlier; varies according to patient)
Secondary Number of ECMO circuit component replacements Replacement of oxygenator and/or pump At 30 days post-randomization
Secondary Presence vs. absence of hemolysis According to plasma hemoglobin values Daily up to 30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient)
Secondary All-cause mortality Death from any cause 30 days, in-hospital, and 1 year post-randomization
Secondary Number of ICU-free days Minimum value is zero, maximum value is 60 minus ICU length of stay At 60 days post-randomization
Secondary Number of hospital-free days Minimum value is zero, maximum value is 60 minus hospital length of stay At 90 days post-randomization
Secondary Discharge location Home vs. rehabilitation facility At time of hospital discharge (assessed up to 1 year)
Secondary 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. 1 year post-randomization (+/- 2 mo)
Secondary Child Behavior Checklist (CBCL) Parent-report; child minimum age 1.5 years. Higher score indicates worse behavior. 1 year post-randomization (+/- 2 mo)
Secondary 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. 9 months post-randomization (+/- 1 mo)
Secondary 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. 9 months post-randomization (+/- 1 mo)
Secondary Number of Donor Exposures Number of Donor Exposures for RBC transfusion Daily up to 30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient)
Secondary Recannulation for ECMO < 48 hours and < 72 hours after decannulation No: of patients recannulated for ECMO within 48 hours and 72 hours post-decannulation From ECMO decannulation hour to 72 hours following ECMO decannulation
Secondary 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 During Hospitalization: From ECMO cannulation to ECMO decannulation, death, transition to Ventricular Assist Device (VAD) or 365 days post-randomization, whichever is earliest
Secondary 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. During Hospitalization: From Randomization to Extubation from Mechanical Ventilation, death, hospital discharge, or 365 days post-randomization, whichever is earliest
Secondary Occurrence of Seizures Occurrence of electroencephalographic evidence of seizure prior to hospital discharge or within 90 d post randomization, whichever is earliest Randomization to Hospital Discharge or 90 days post-randomization, whichever is earliest
Secondary 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 of ECMO cannulation to ECMO decannulation, death or 30 days post-randomization, whichever occurs first
Secondary 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 ECMO cannulation to 90 days post-randomization or hospital discharge, whichever occurs first
Secondary 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. Randomization to study completion (completion of 12 month neurodevelopment assessment)
Secondary 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 Randomization to study completion (completion of 12 month neurodevelopment assessment)
Secondary ICU Length of Stay among survivors Duration of hospitalization in the ICU among survivors in days. For ICU readmissions only the only days in the first 2 ICU readmissions will be included ICU Admission to ICU discharge, death or 365 post-randomization, whichever occurs first
Secondary Hospital length of stay among survivors Duration of hospitalization among survivors in days Hospital Admission to discharge death, or 365 days post-randomization, whichever occurs first
Secondary 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. Randomization to study completion (completion of 12 month neurodevelopment assessment)
Secondary Number of ICU readmissions prior to discharge from index hospitalization among survivors Number of ICU readmissions. ICU readmissions are defined as number of ICU admissions following discharge from the first ICU admission. Index ICU discharge to Hospital discharge or 365 days post-randomization, whichever occurs first
See also
  Status Clinical Trial Phase
Completed NCT03685383 - Cytokine Adsorption in Post-cardiac Arrest Syndrome in Patients Requiring Extracorporeal Cardiopulmonary Resuscitation N/A
Not yet recruiting NCT05106491 - Efficacy and Safety of Synchronized Cardiac Support in Cardiogenic Shock Patients N/A
Recruiting NCT05699005 - Individualized or Conventional Transfusion Strategies During Peripheral VA-ECMO Phase 1
Recruiting NCT05444764 - PREdiCtIon of Weanability, Survival and Functional outcomEs After ECLS
Completed NCT05038943 - Evaluation of Safety and Effectiveness of The SherpaPak in Donation After Circulatory Death Heart Transplantation N/A
Not yet recruiting NCT05341687 - Prognostic Value of Respiratory System Compliance Under VV-ECMO on 180-day Mortality in COVID-19 ARDS.
Suspended NCT04385771 - Cytokine Adsorption in Patients With Severe COVID-19 Pneumonia Requiring Extracorporeal Membrane Oxygenation N/A
Recruiting NCT03766282 - Pharmacokinetics in Extracorporeal Membrane Oxygenation
Completed NCT03355625 - Platelet Function During Extracorporeal Membrane Oxygenation in Adult Patients
Completed NCT01521195 - Oxygen Consumption In Critically Ill Children N/A
Recruiting NCT04620070 - ON-SCENE Initiation of Extracorporeal CardioPulmonary Resuscitation During Refractory Out-of-Hospital Cardiac Arrest N/A
Recruiting NCT06062212 - Effect of Transpulmonary MP on Prognosis of Patients With Severe ARDS Treated With VV-ECMO
Recruiting NCT05730114 - Monitoring Antiplatelet Drugs in Cardiac Arrest Patients
Completed NCT05154071 - Impact of the Implementation of a Referral Veno-venous Extracorporeal Membrane Oxygenation Centre on Mortality
Recruiting NCT04536272 - Reduced Anticoagulation Targets in ECLS (RATE) Phase 3
Completed NCT05693051 - Use of Prone Position Ventilation in Danish Patients With COVID-19 Induced Severe ARDS Treated With VV-ECMO
Completed NCT03764319 - Low Frequency, Ultra-low Tidal Volume Ventilation in Patients With ARDS and ECMO N/A
Recruiting NCT05762029 - Treatment of Extracorporeal Membrane Oxygenation in Severe Poisoning
Completed NCT02995811 - Characterising Changes in Muscle Quantity and Quality in Patients Requiring ECMO Oxygen During Critical Illness
Recruiting NCT04754854 - Reduction of Blood Recirculation in Veno-Venous ECMO