NCT Number: NCT01702805
Transfusion of Prematures Trial
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.
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Notify MeKey information
Conditions
Age range
Up to 48 hour
Sex eligibility
All sexes
Study type
Interventional
Phase
Not applicable
Primary location
University of Alabama at Birmingham, Birmingham, Alabama, United States
About this study
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.
Who can participate
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
- 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
Exclusion criteria
- 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.
Treatment and study plan
Restricted red cell transfusion
ProcedurePrimary outcomes
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Death or Neurodevelopmental Impairment
Time frame: 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.
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Death
Time frame: 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
Time frame: 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.
-
Cognitive Delay
Time frame: 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.
-
Moderate or Severe Cerebral Palsy
Time frame: 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.
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Severe Vision Impairment
Time frame: 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.
-
Severe Hearing Impairment
Time frame: 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.
Secondary outcomes
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Survival to Discharge Without Severe Complications
Time frame: Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)
This is measured as Yes if survived to discharge without severe morbidity, defined as bronchopulmonary dysplasia, retinopathy of prematurity (stage 3 or higher or requiring treatment), or serious brain abnormality; Otherwise, No.
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Bronchopulmonary Dysplasia, Diagnosed on the Basis of the Need for Supplemental Oxygen After a Standardized Oxygen Reduction Test at 36 Weeks of Postmenstrual Age
Time frame: at 36 weeks postmenstrual age
This is measured as Yes if experienced bronchopulmonary dysplasia, diagnosed on the basis of the need for supplemental oxygen after a standardized oxygen reduction test at 36 weeks of postmenstrual age; Otherwise, No.
-
Retinopathy of Prematurity Stage >=3 or Treatment for That Condition Received
Time frame: Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)
This is measured as Yes if experienced Retinopathy of Prematurity (ROP) Stage >=3 or received treatment for that condition; Otherwise, No. Higher stages of ROP indicate a worse outcome; the stages range from 1 for "mild" disease, to 5 for "severe" disease.
-
Grade 3 or 4 Intraventricular Hemorrhage, Cystic Periventricular Leukomalacia, or Ventriculomegaly Diagnosed on Ultrasonographic Examination
Time frame: Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)
This is measured as Yes if experienced Grade 3 or 4 intraventricularhemorrhage, cystic periventricular leukomalacia, or ventriculomegaly diagnosed on ultrasonographic examination; Otherwise, No.
-
Necrotizing Enterocolitis, Bell's Stage >=2
Time frame: Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)
This is measured as Yes if experienced necrotizing enterocolitis (NEC), Bell's stage >=2; Otherwise, No. Higher scores of Bell's staging criteria denote a worse outcome, where "1" denotes suspect, "2" definite and "3" advanced NEC.
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Number of Transfusions Per Infant
Time frame: Birth, up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age (PMA)
This is measured as the number of protocol compliant transfusions, clinically justified non-protocol transfusions and unjustified non-protocol transfusions (violations)
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Weight-for-age: Z-score
Time frame: at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first
This is measured as the weight-for-age Z-score at 36 weeks postmenstrual age or at initial hospital discharge, whichever occurs first. The Z-score is determined using Olsen percentile curves, and is derived from a normal distribution, where 0 designates average weight-for-age, and negative scores denote less than average weight-for-age.
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Length-for-age: Z-score
Time frame: at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first
This is measured as the length-for-age Z-score at 36 weeks postmenstrual age or at initial hospital discharge, whichever occurs first. The Z-score is determined using Olsen percentile curves, and is derived from a normal distribution, where 0 designates average length-for-age, and negative scores denote less than average length-for-age.
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Head Circumference-for-age: Z-score
Time frame: at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first
This is measured as the head circumference-for-age Z-score at 36 weeks postmenstrual age or at initial hospital discharge, whichever occurs first. The Z-score is determined using Olsen percentile curves, and is derived from a normal distribution, where 0 designates average head circumference-for-age, and negative scores denote less than average head circumference-for-age.
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Postmenstrual Age at Final Trachael Extubation
Time frame: at final trachael extubation, assessed from birth up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age
This is measured as the average postmenstrual age (in weeks) at final tracheal extubation in infants who were intubated.
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Postmenstrual Age at Final Caffeine Dose in Infants Who Received Caffeine Treatment
Time frame: at final caffeine dose, assessed from birth up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age
This is measured as the average postmenstrual age (in weeks) at final caffeine dose in infants who received caffeine treatment.
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Length of Stay
Time frame: at initial hospital discharge or at death if it occurs earlier (a median of 97 days)
This is measured as the length of stay (in days) up to initial hospital discharge or death, whichever occurred first.
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Time to Full Enteral Feeding
Time frame: 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)
This is measured as the amount of days it took for full enteral feeding to occur.
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Severe Cerebral Palsy
Time frame: at 22-26 months corrected age
This is measured as Yes if Gross Motor Function Classification System (GMFCS) is levels IV or V; 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.
-
Hydrocephalus Shunt
Time frame: Initial hospital discharge to 22-26 months corrected age
This is measured as Yes if experienced Hydrocephalus shunt by follow-up; Otherwise, No.
-
Microcephaly
Time frame: at 22-26 months corrected age
This is measured as a head circumference-for-age Z-score of less than -2; Otherwise, No. The Z-score is determined using WHO percentile curves, and is derived from a normal distribution, where 0 designates average head circumference-for-age, and negative scores denote less than average head circumference-for-age.
-
Seizure Disorder
Time frame: Initial hospital discharge to 22-26 months corrected age
This is measured as Yes if experienced one or more seizures since discharge or of regular use of anticonvulsants or seizure medications; Otherwise, No.
-
Respiratory Disease Necessitating Readmission Before Follow-up
Time frame: Initial hospital discharge to 22-26 months corrected age
This is measured as Yes if obtained Respiratory disease necessitating readmission before follow-up; Otherwise, No.
-
Composite Language Score Less Than 85
Time frame: at 22-26 months corrected age
This is measured as Yes if scored less than 85 on the Bayley Scale of Infant and Toddler Development (BSID)-III composite language score; Otherwise, No. Higher scores indicate better performance. Composite BSID-III scores of less than 85 are less than 1 standard deviation below the mean of 100.
-
Composite Motor Score Less Than 85
Time frame: at 22-26 months corrected age
This is measured as Yes if scored less than 85 on the Bayley Scale of Infant and Toddler Development (BSID)-III composite motor score; Otherwise, No. Higher scores indicate better performance. Composite BSID-III scores of less than 85 are less than 1 standard deviation below the mean of 100.
-
Composite Cognitive Score Less Than 70
Time frame: at 22-26 months corrected age
This is measured as Yes if scored less than 85 on the Bayley Scale of Infant and Toddler Development (BSID)-III composite cognitive score; Otherwise, No. Higher scores indicate better performance. Composite BSID-III scores of less than 70 are less than 2 standard deviations below the mean of 100.
-
Composite Language Score Less Than 70
Time frame: at 22-26 months corrected age
This is measured as Yes if scored less than 85 on the Bayley Scale of Infant and Toddler Development (BSID)-III composite language score; Otherwise, No. Higher scores indicate better performance. Composite BSID-III scores of less than 70 are less than 2 standard deviations below the mean of 100.
-
Composite Motor Score Less Than 70
Time frame: at 22-26 months corrected age
This is measured as Yes if scored less than 85 on the Bayley Scale of Infant and Toddler Development (BSID)-III composite motor score; Otherwise, No. Higher scores indicate better performance. Composite BSID-III scores of less than 70 are less than 2 standard deviations below the mean of 100.
Sponsors and collaborators
Lead sponsor
NICHD Neonatal Research Network
Network
Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- National Heart, Lung, and Blood Institute (NHLBI)
Registry information
Official study title
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?
Acronym: TOP
Important dates
- Study start
- 2012
- Primary completion
- 2020
- Study completion
- 2025
- First posted
- Oct 8, 2012
- Registry last updated
- Nov 14, 2025
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
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