Share
Save
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.
Study details:
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
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 0 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2023-04-14
Primary completion: 2024-10-01
Study completion finish: 2025-12-01
Study type
OTHER
Phase
NA
Trial ID
NCT05405426
Intervention or treatment
OTHER: Red blood cell transfusion
Conditions
- • Extracorporeal Membrane Oxygenation
- • Red Blood Cell Transfusion
- • Organ Failure, Multiple
Find a site
Closest Location:
The Children's Hospital at Westmead
Research sites nearby
Select from list below to view details:
The Children's Hospital at Westmead
Westmead, New South Wales, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
ACTIVE_COMPARATOR: Indication-based red blood cell transfusion strategy
| OTHER: Red blood cell transfusion
|
OTHER: Center-specific hemoglobin/hematocrit threshold-based red blood cell transfusion strategy
| OTHER: Red blood cell transfusion
|
What is the study measuring?
Primary outcome
| Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
|---|---|---|
| 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 outcome
| Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
|---|---|---|
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| Number of ECMO circuit component replacements | Replacement of oxygenator and/or pump | At 30 days post-randomization |
| 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) |
| All-cause mortality | Death from any cause | 30 days, in-hospital, and 1 year post-randomization |
| Discharge location | Home vs. rehabilitation facility | At time of hospital discharge (assessed up to 1 year) |
| 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) |
| Child Behavior Checklist (CBCL) | Parent-report; child minimum age 1.5 years. Higher score indicates worse behavior. | 1 year post-randomization (+/- 2 mo) |
| 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) |
| 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) |
| 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) |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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) |
| 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) |
| ICU Length of Stay among survivors during index hospitalization | Duration of hospitalization in the ICU among survivors in days during index hospitalization. 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 |
| Hospital length of stay among survivors during index hospitalization | Duration of hospitalization among survivors in days during index hospitalization | Hospital Admission to discharge death, or 365 days post-randomization, whichever occurs first |
| 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) |
| Number of ICU admissions prior to discharge from index hospitalization among survivors | Number of ICU admissions during index hospitalization. ICU admissions 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 |
Frequently Asked Questions
Please note: some questions and answers are submitted by anonymous patients or using AI, and have not been verified by Clinrol
No questions submitted. Be the first to ask a question!