Transfusion of Prematures (TOP) Trial: Does a Liberal Red Blood Cell Transfusion Strategy Improve Neurologically-Intact Survival of Extremely-Low-Birth-Weight Infants as Compared to a Restrictive Strategy?
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 1,824
- 试验地点
- 40
- 主要终点
- Death
研究概览
简要总结
The objective of the TOP trial is to determine whether higher hemoglobin thresholds for transfusing ELBW infants resulting in higher hemoglobin levels lead to improvement in the primary outcome of survival and rates of neurodevelopmental impairment (NDI) at 22-26 months of age, using standardized assessments by Bayley.
详细描述
Long-term outcomes of extremely low birth weight (ELBW) preterm infants, those weighing less than or equal to 1000 g at birth, are poor and pose a major health care burden. Virtually all of these infants are transfused, but at inconsistent hemoglobin (Hgb) thresholds.
The investigators propose in TOP to randomize infants less than or equal to 1000 g BW and gestational age at least 22 weeks but less than 29 weeks to receive red blood cell (RBC) transfusions according to one of two strategies of Hgb thresholds, either a high Hgb (liberal transfusion) or a low Hgb (restrictive transfusion) algorithm. It is currently unknown which transfusion strategy is superior. TOP is powered to demonstrate which strategy reduces the primary outcome of death or neurodisability in survivors at 22-26 months.
A secondary study entitled "Effect of Blood Transfusion Practices on Cerebral and Somatic Oximetry", also known as the NIRS study, will determine differences in cerebral oxygenation and fractional tissue oxygen extraction with NIRS between high and low hemoglobin threshold groups during red blood cell transfusions. The investigators also propose to determine whether abnormal cerebral NIRS measures are a better predictor of NDI than hemoglobin alone and whether abnormal mesenteric NIRS measures are associated with the development of NEC within the 48 hours following a transfusion.
A secondary study entitled "Economic Evaluation Ancillary to the Transfusion of Prematures Randomized Controlled Trial" will determine whether higher transfusion threshold will result in lower total costs to society over the first 22 to 26 corrected months of life and estimate the incremental cost-effectiveness ratio for survival without neurodevelopmental impairment, from the perspective of society, the third-party payer, and the family.
Extended follow-up: Subjects will be seen for a follow-up visit at 5-6 years corrected age to assess neurological and functional outcomes at early school age based on neonatal transfusion threshold.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- — 至 48 Hours（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Birth weight less than or equal to 1000 grams.
- •Gestational age at least 22 weeks but less than 29 weeks
- •Admitted to the NICU within 48 hours of life
排除标准
- •Considered nonviable by the attending neonatologist
- •Cyanotic congenital heart disease
- •Parents opposed to the transfusion of blood
- •Parents with hemoglobinopathy or congenital anemia
- •In-utero fetal transfusion
- •Twin-to-twin transfusion syndrome
- •Isoimmune hemolytic disease
- •Lack of parental consent
- •Severe acute hemorrhage, acute shock, sepsis with coagulopathy, or need for perioperative transfusion.
- •Prior blood transfusion on clinical grounds beyond the first 6 hours of life
- •Infant has received erythropoietin prior to randomization, or is intended to receive erythropoietin through the neonatal course
- •Congenital condition, other than premature birth, that adversely affects life expectancy or neurodevelopment.
- •High probability that the family is socially disorganized to the point of being unable to attend follow-up at 22-26 months.
结局指标
主要结局
Death
时间窗: Birth to 22-26 months corrected age
This is measured as Yes if an infant died between birth and 22-26 months corrected age; Otherwise, No.
Neurodevelopmental Impairment
时间窗: at 22-26 months corrected age
This is measured as Yes if any hearing impairment or visual impairment is noted, if severe or moderate cerebral palsy is noted, or if the cognitive score of the Bayley III score is more than 1 standard deviation below the average; Otherwise, No.
Moderate or Severe Cerebral Palsy
时间窗: at 22-26 months corrected age
This is measured as Yes if the Gross Motor Function Classification System (GMFCS) score is level II or higher; Otherwise, No. Higher values of the GMFCS are worse than lower values; a level of "I" denotes mild cerebral palsy (CP); level "II" or "III" moderate CP; level "IV" or "V" severe CP.
Severe Hearing Impairment
时间窗: at 22-26 months corrected age
This is measured as Yes if bilateral hearing loss occurred for which hearing aids or cochlear implants were warranted; Otherwise, No.
Death or Neurodevelopmental Impairment
时间窗: Birth to 22-26 months corrected age
A composite outcome that measures the occurrence of death or neurodevelomental impairment between birth and 22-26 months corrected age.
Cognitive Delay
时间窗: at 22-26 months corrected age
This is measured as Yes if the Bayley Scale of Infant and Toddler Development (BSID)-III cognitive score is more than 1 standard deviation below the average; Otherwise, No.
Severe Vision Impairment
时间窗: at 22-26 months corrected age
This is measured as Yes if the corrected visual acuity in the better eye of less than 20/200; Otherwise, No.
次要结局
- Survival to Discharge Without Severe Complications(Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days))
- Weight-for-age: Z-score(at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first)
- Head Circumference-for-age: Z-score(at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first)
- Postmenstrual Age at Final Caffeine Dose in Infants Who Received Caffeine Treatment(at final caffeine dose, assessed from birth up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age)
- Composite Motor Score Less Than 85(at 22-26 months corrected age)
- Composite Language Score Less Than 70(at 22-26 months corrected age)
- Composite Motor Score Less Than 70(at 22-26 months corrected age)
- Retinopathy of Prematurity Stage >=3 or Treatment for That Condition Received(Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days))
- Grade 3 or 4 Intraventricular Hemorrhage, Cystic Periventricular Leukomalacia, or Ventriculomegaly Diagnosed on Ultrasonographic Examination(Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days))
- Length-for-age: Z-score(at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first)
- Hydrocephalus Shunt(Initial hospital discharge to 22-26 months corrected age)
- Respiratory Disease Necessitating Readmission Before Follow-up(Initial hospital discharge to 22-26 months corrected age)
- Composite Language Score Less Than 85(at 22-26 months corrected age)
- Bronchopulmonary Dysplasia, Diagnosed on the Basis of the Need for Supplemental Oxygen After a Standardized Oxygen Reduction Test at 36 Weeks of Postmenstrual Age(at 36 weeks postmenstrual age)
- Necrotizing Enterocolitis, Bell's Stage >=2(Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days))
- Number of Transfusions Per Infant(Birth, up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age (PMA))
- Postmenstrual Age at Final Trachael Extubation(at final trachael extubation, assessed from birth up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age)
- Length of Stay(at initial hospital discharge or at death if it occurs earlier (a median of 97 days))
- Time to Full Enteral Feeding(at first full enteral feeding, assessed from birth up to initial hospital discharge or to death if it occurs earlier (a median of 97 days))
- Severe Cerebral Palsy(at 22-26 months corrected age)
- Microcephaly(at 22-26 months corrected age)
- Seizure Disorder(Initial hospital discharge to 22-26 months corrected age)
- Composite Cognitive Score Less Than 70(at 22-26 months corrected age)