Extracorporeal Membrane Oxygenation Clinical Trial
— TITREOfficial title:
TITRE: Trial of Indication-Based Transfusion of Red Blood Cells in ECMO
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.
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 |
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 |
Lead Sponsor | Collaborator |
---|---|
Boston Children's Hospital |
United States, Australia, Canada,
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 |
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