TITRE: Trial of Indication-Based Transfusion of Red Blood Cells in ECMO
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 228
- 试验地点
- 43
- 主要终点
- Bayley Infant Scales of Development, 4th edition (Bayley-4)
研究概览
简要总结
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.
详细描述
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 22 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 240 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Single (Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 0 Days 至 6 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age < 6 year at ECMO cannulation
- •Veno-arterial (VA) mode of ECMO
- •First ECMO run during the index hospitalization
排除标准
- •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
- •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
- •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).
研究组 & 干预措施
Indication-based red blood cell transfusion strategy
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.
干预措施: Red blood cell transfusion (Other)
Center-specific hemoglobin/hematocrit threshold-based red blood cell transfusion strategy
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.
干预措施: Red blood cell transfusion (Other)
结局指标
主要结局
Bayley Infant Scales of Development, 4th edition (Bayley-4)
时间窗: One year post-randomization (+/- 2 mo)
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.
Wechsler Preschool and Primary Scale of Intelligence (WPPSI - IV)
时间窗: One year post-randomization (+/-2 mo)
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.
Baseline-adjusted change in pSOFA (pediatric Sequential Organ Failure Assessment) score
时间窗: At randomization and at 30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient)
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.
次要结局
- 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))
- Number of ECMO circuit component replacements(At 30 days post-randomization)
- Presence vs. absence of hemolysis(Daily up to 30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient))
- All-cause mortality(30 days, in-hospital, and 1 year post-randomization)
- Discharge location(At time of hospital discharge (assessed up to 1 year))
- Adaptive Behavior Assessment System-3 (ABAS-3)(1 year post-randomization (+/- 2 mo))
- Child Behavior Checklist (CBCL)(1 year post-randomization (+/- 2 mo))
- Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0)(9 months post-randomization (+/- 1 mo))
- Pediatric Quality of Life Inventory Cardiac Module(9 months post-randomization (+/- 1 mo))
- Number of Donor Exposures(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(From ECMO decannulation hour to 72 hours following ECMO decannulation)
- 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(During Hospitalization: From Randomization to Extubation from Mechanical Ventilation, death, hospital discharge, or 365 days post-randomization, whichever is earliest)
- Occurrence of Seizures(Randomization to Hospital Discharge or 90 days post-randomization, whichever is earliest)
- Stroke or Intracranial Hemorrhage 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(ECMO cannulation to 90 days post-randomization or hospital discharge, whichever occurs first)
- Pediatric Overall Performance Category (POPC)(Randomization to study completion (completion of 12 month neurodevelopment assessment))
- Functional Status Score (FSS)(Randomization to study completion (completion of 12 month neurodevelopment assessment))
- ICU Length of Stay among survivors during index hospitalization(ICU Admission to ICU discharge, death or 365 post-randomization, whichever occurs first)
- Hospital length of stay among survivors during index hospitalization(Hospital Admission to discharge death, or 365 days post-randomization, whichever occurs first)
- Pediatric Cerebral Performance Category (PCPC)(Randomization to study completion (completion of 12 month neurodevelopment assessment))
- Number of ICU admissions prior to discharge from index hospitalization among survivors(Index ICU discharge to Hospital discharge or 365 days post-randomization, whichever occurs first)
- Presence vs. absence of hospital-acquired blood stream Infection(30 days post-randomization (up to time of ECMO decannulation if earlier; varies according to patient))
- Proportion of ECMO days meeting moderate - severe bleeding criteria(Daily up to 30 days post-randomization (or up to time of ECMO decannulation if earlier; varies according to patient))
研究者
Ravi Thiagarajan
Professor/Division of Cardiovascular Critical Care, Dept. of Cardiology
Boston Children's Hospital