Infant, Newborn, DiseasesTOPNCT01702805

Transfusion of Prematures Trial

A study testing Liberal Cell Transfusion and Restricted red cell transfusion in people with Infant, Newborn, Diseases and Infant, Extremely Low Birth Weight, run by NICHD Neonatal Research Network at 20 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages Up to 48 hours
Conditions the study is for: Infant, Newborn, Diseases, Infant, Extremely Low Birth Weight, Infant, Small for Gestational Age
What is being tested?: Liberal Cell Transfusion and Restricted red cell transfusion
Type of treatment: Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 1,824 participants
Where: 20 sitesUnited States
Study dates: Dec 2012to 29 Apr 2025
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Up to 48 hours
All sexes
No healthy volunteers
Child

Who may be able to join

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

Who cannot join

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

Show all 13Show fewer

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.

Trial locations and contacts

20 sites in 1 country.

City, postcode or hospital

20 sites in 1 country

United States20 sites

University of New Mexico
Albuquerque, New Mexico, 87131
Emory University
Atlanta, Georgia, 30303
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Cincinnati Children's Medical Center
Cincinnati, Ohio, 45267
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, 44106
Research Institute at Nationwide Children's Hospital
Columbus, Ohio, 43205
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75235
Wayne State University
Detroit, Michigan, 48201
RTI International
Durham, North Carolina, 27705
Duke University
Durham, North Carolina, 27710
University of Texas Health Science Center at Houston
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 46202
University of Iowa
Iowa City, Iowa, 52242
Children's Mercy Hospital
Kansas City, Missouri, 64108
University of California - Los Angeles
Los Angeles, California, 90025
Stanford University
Palo Alto, California, 94304
Univeristy of Pennsylvania
Philadelphia, Pennsylvania, 19104
Brown University, Women & Infants Hospital of Rhode Island
Providence, Rhode Island, 02905
University of Rochester
Rochester, New York, 14642
University of Utah
Salt Lake City, Utah, 84108

Other trials in United States

About this study

Official 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?

Read the detailed description

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.

Conditions: Infant, Newborn, Diseases, Infant, Extremely Low Birth Weight, Infant, Small for Gestational Age, Bronchopulmonary Dysplasia (BPD), Anemia
Being tested: Liberal Cell Transfusion, Restricted red cell transfusion
Keywords: NICHD Neonatal Research Network, Very Low Birth Weight (VLBW), Extremely Low Birth Weight (ELBW), Transfusions
Medical subject headings: Infant, Newborn, Diseases, Bronchopulmonary Dysplasia, Anemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Liberal Cell TransfusionProcedure or surgery
Restricted red cell transfusionProcedure or surgery

Study groups in NCT01702805
Study group	Role	What they receive
Low Threshold Transfusion	Active comparator	Transfusions will be administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group Receives: Procedure: Restricted red cell transfusion
High Threshold Transfusion	Active comparator	Transfusions will be administered using a higher threshold hemoglobin value. Receives: Procedure: Liberal Cell Transfusion

What is being measured

The primary outcome is the main question the study is designed to answer.

Death or Neurodevelopmental Impairment
A composite outcome that measures the occurrence of death or neurodevelomental impairment between birth and 22-26 months corrected age.
Measured: Birth to 22-26 months corrected age
Death
This is measured as Yes if an infant died between birth and 22-26 months corrected age; Otherwise, No.
Measured: Birth to 22-26 months corrected age
Neurodevelopmental Impairment
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.
Measured: at 22-26 months corrected age
Cognitive Delay
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.
Measured: at 22-26 months corrected age
Moderate or Severe Cerebral Palsy
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.
Measured: at 22-26 months corrected age
Severe Vision Impairment
This is measured as Yes if the corrected visual acuity in the better eye of less than 20/200; Otherwise, No.
Measured: at 22-26 months corrected age
Severe Hearing Impairment
This is measured as Yes if bilateral hearing loss occurred for which hearing aids or cochlear implants were warranted; Otherwise, No.
Measured: at 22-26 months corrected age

Secondary outcomes (23)

Survival to Discharge Without Severe Complications
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.
Measured: Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)
Bronchopulmonary Dysplasia, Diagnosed on the Basis of the Need for Supplemental Oxygen After a Standardized Oxygen Reduction Test at 36 Weeks of 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.
Measured: at 36 weeks postmenstrual age
Retinopathy of Prematurity Stage >=3 or Treatment for That Condition Received
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.
Measured: 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
This is measured as Yes if experienced Grade 3 or 4 intraventricularhemorrhage, cystic periventricular leukomalacia, or ventriculomegaly diagnosed on ultrasonographic examination; Otherwise, No.
Measured: Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)
Necrotizing Enterocolitis, Bell's Stage >=2
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.
Measured: Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)
Number of Transfusions Per Infant
This is measured as the number of protocol compliant transfusions, clinically justified non-protocol transfusions and unjustified non-protocol transfusions (violations)
Measured: Birth, up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age (PMA)
Weight-for-age: Z-score
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.
Measured: at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first
Length-for-age: Z-score
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.
Measured: at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first
Head Circumference-for-age: Z-score
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.
Measured: at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first
Postmenstrual Age at Final Trachael Extubation
This is measured as the average postmenstrual age (in weeks) at final tracheal extubation in infants who were intubated.
Measured: at final trachael extubation, assessed from birth up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age
Postmenstrual Age at Final Caffeine Dose in Infants Who Received Caffeine Treatment
This is measured as the average postmenstrual age (in weeks) at final caffeine dose in infants who received caffeine treatment.
Measured: at final caffeine dose, assessed from birth up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age
Length of Stay
This is measured as the length of stay (in days) up to initial hospital discharge or death, whichever occurred first.
Measured: at initial hospital discharge or at death if it occurs earlier (a median of 97 days)
Time to Full Enteral Feeding
This is measured as the amount of days it took for full enteral feeding to occur.
Measured: 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
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.
Measured: at 22-26 months corrected age
Hydrocephalus Shunt
This is measured as Yes if experienced Hydrocephalus shunt by follow-up; Otherwise, No.
Measured: Initial hospital discharge to 22-26 months corrected age
Microcephaly
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.
Measured: at 22-26 months corrected age
Seizure Disorder
This is measured as Yes if experienced one or more seizures since discharge or of regular use of anticonvulsants or seizure medications; Otherwise, No.
Measured: Initial hospital discharge to 22-26 months corrected age
Respiratory Disease Necessitating Readmission Before Follow-up
This is measured as Yes if obtained Respiratory disease necessitating readmission before follow-up; Otherwise, No.
Measured: Initial hospital discharge to 22-26 months corrected age
Composite Language Score Less Than 85
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.
Measured: at 22-26 months corrected age
Composite Motor Score Less Than 85
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.
Measured: at 22-26 months corrected age
Composite Cognitive Score Less Than 70
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.
Measured: at 22-26 months corrected age
Composite Language Score Less Than 70
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.
Measured: at 22-26 months corrected age
Composite Motor Score Less Than 70
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.
Measured: at 22-26 months corrected age

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 201229 Apr 2025

First posted8 Oct 2012 (estimated)
Study startDec 2012
Primary completionJan 2020
Study completion29 Apr 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Infant, Newborn, DiseasesStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 1,824 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01702805
Sponsor's protocol ID: NICHD-NRN-0050
Other IDs: U01HL112776, U01HL112748
Acronym: TOP
Status last verified: Nov 2025
First submitted: 30 Aug 2012
Last updated: 14 Nov 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: NIH has had a long-standing policy to share and make available to the public the results and accomplishments of the activities that it funds. The NRN plans to share de-identified data after final publication in an NIH supported data repository such as the NICHD Data and Specimen Hub (https://dash.nichd.nih.gov)

Publications

Conrad AL, DeMauro SB, Kirpalani H, Ziolkowski K, Hintz SR, Vohr BR, Watson V, Colaizy TT, Bell EF, Brumbaugh JE, Bann CM, Tan SM, Newman JE, Das A. The transfusion of prematures early school age follow-up (TOP 5): protocol for a longitudinal cohort study. BMC Pediatr. 2025 May 15;25(1):387. doi: 10.1186/s12887-025-05732-3.
PubMed 40375228
Salas AA, Gunn E, Carlo WA, Bell EF, Das A, Josephson CD, Patel RM, Tan S, Kirpalani H; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network. Timing of Red Blood Cell Transfusions and Occurrence of Necrotizing Enterocolitis: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2024 May 1;7(5):e249643. doi: 10.1001/jamanetworkopen.2024.9643.
PubMed 38700862
Chock VY, Kirpalani H, Bell EF, Tan S, Hintz SR, Ball MB, Smith E, Das A, Loggins YC, Sood BG, Chalak LF, Wyckoff MH, Kicklighter SD, Kennedy KA, Patel RM, Carlo WA, Johnson KJ, Watterberg KL, Sanchez PJ, Laptook AR, Seabrook RB, Cotten CM, Mancini T, Sokol GM, Ohls RK, Hibbs AM, Poindexter BB, Reynolds AM, DeMauro SB, Chawla S, Baserga M, Walsh MC, Higgins RD, Van Meurs KP; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Tissue Oxygenation Changes After Transfusion and Outcomes in Preterm Infants: A Secondary Near-Infrared Spectroscopy Study of the Transfusion of Prematures Randomized Clinical Trial (TOP NIRS). JAMA Netw Open. 2023 Sep 5;6(9):e2334889. doi: 10.1001/jamanetworkopen.2023.34889.
PubMed 37733345
Kirpalani H, Bell EF, Hintz SR, Tan S, Schmidt B, Chaudhary AS, Johnson KJ, Crawford MM, Newman JE, Vohr BR, Carlo WA, D'Angio CT, Kennedy KA, Ohls RK, Poindexter BB, Schibler K, Whyte RK, Widness JA, Zupancic JAF, Wyckoff MH, Truog WE, Walsh MC, Chock VY, Laptook AR, Sokol GM, Yoder BA, Patel RM, Cotten CM, Carmen MF, Devaskar U, Chawla S, Seabrook R, Higgins RD, Das A; Eunice Kennedy Shriver NICHD Neonatal Research Network. Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants. N Engl J Med. 2020 Dec 31;383(27):2639-2651. doi: 10.1056/NEJMoa2020248.
PubMed 33382931

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 14 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official 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?
ClinicalTrials.gov ID: NCT01702805
Acronym / sponsor ID: TOP / NICHD-NRN-0050
Conditions: Infant, Newborn, Diseases, Infant, Extremely Low Birth Weight, Infant, Small for Gestational Age, Bronchopulmonary Dysplasia (BPD), Anemia
Keywords: NICHD Neonatal Research Network, Very Low Birth Weight (VLBW), Extremely Low Birth Weight (ELBW), Transfusions
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,824 participants (actual)
Lead sponsor: NICHD Neonatal Research NetworkResearch network
Collaborators: National Heart, Lung, and Blood Institute (NHLBI), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study start: Dec 2012 (actual)
Primary completion: Jan 2020 (actual)
Study completion: 29 Apr 2025 (actual)
First posted: 8 Oct 2012 (estimated)
Results: Posted 11 Feb 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Low Threshold Transfusion	Active comparator	Procedure: Restricted red cell transfusionTransfusions will be administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group
High Threshold Transfusion	Active comparator	Procedure: Liberal Cell TransfusionTransfusions will be administered using a higher threshold hemoglobin value.

Who may qualify

Ages: Up to 48 hours
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (3 listed)

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

Key exclusion criteria (13 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Liberal Cell Transfusion	Procedure or surgery	High Threshold Transfusion
Restricted red cell transfusion	Procedure or surgery	Low Threshold Transfusion

Primary outcome

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.
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.
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.

23 secondary outcomes

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)
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
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)
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)
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)
Number of Transfusions Per Infant
Time frame: Birth, up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age (PMA)
Weight-for-age: Z-score
Time frame: at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first
Length-for-age: Z-score
Time frame: at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first
Head Circumference-for-age: Z-score
Time frame: at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first
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
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
Length of Stay
Time frame: at initial hospital discharge or at death if it occurs earlier (a median of 97 days)
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)
Severe Cerebral Palsy
Time frame: at 22-26 months corrected age
Hydrocephalus Shunt
Time frame: Initial hospital discharge to 22-26 months corrected age
Microcephaly
Time frame: at 22-26 months corrected age
Seizure Disorder
Time frame: Initial hospital discharge to 22-26 months corrected age
Respiratory Disease Necessitating Readmission Before Follow-up
Time frame: Initial hospital discharge to 22-26 months corrected age
Composite Language Score Less Than 85
Time frame: at 22-26 months corrected age
Composite Motor Score Less Than 85
Time frame: at 22-26 months corrected age
Composite Cognitive Score Less Than 70
Time frame: at 22-26 months corrected age
Composite Language Score Less Than 70
Time frame: at 22-26 months corrected age
Composite Motor Score Less Than 70
Time frame: at 22-26 months corrected age

Results and safety

Results posted to the registry on 11 Feb 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
High Tranfusion Threshold	911	845
Low Transfusion Threshold	913	847

Primary outcome: Death or Neurodevelopmental Impairment

Time frame: Birth to 22-26 months corrected age. Count of participants. Unit: Participants

Measure	High Transfusion Threshold n = 845	Low Transfusion Threshold n = 847
Death or Neurodevelopmental Impairment	423	422
No Death nor Neurodevelopmental Impairment	422	425

Low Transfusion Threshold: Risk Ratio (RR): 1.00 (95% CI 0.92 to 1.10), p = 0.93, Robust Poisson Regression

Population analysed: The analysis population includes all randomized infants with available data for death and/or neurodevelopmental impairment.

Primary outcome: Death

Time frame: Birth to 22-26 months corrected age. Count of participants. Unit: Participants

Measure	High Transfusion Threshold n = 903	Low Transfusion Threshold n = 901
Death	146	135
No Death	757	766

Population analysed: The analysis population includes all randomized infants with available vital status.

Primary outcome: Neurodevelopmental Impairment

Time frame: at 22-26 months corrected age. Count of participants. Unit: Participants

Measure	High Transfusion Threshold n = 699	Low Transfusion Threshold n = 712
Neurodevelopmental Impairment	277	287
No Neurodevelopmental Impairment	422	425

Population analysed: The analysis population includes all randomized infants with available data for neurodevelopmental impairment.

Primary outcome: Cognitive Delay

Time frame: at 22-26 months corrected age. Count of participants. Unit: Participants

Measure	High Transfusion Threshold n = 695	Low Transfusion Threshold n = 712
Cognitive Delay	269	270
No Cognitive Delay	426	442

Population analysed: The analysis population includes all randomized infants with available data at the two-year followup.

23 secondary outcomes are reported in the full results.

Adverse events

Time frame: Birth to 37 weeks PMA. Other adverse events reported at 0.05% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
High Tranfusion Threshold	206 of 908 (22.7%)	184 of 908 (20.3%)	146 of 903
Low Transfusion Threshold	197 of 906 (21.7%)	164 of 906 (18.1%)	135 of 901

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 40375228Conrad AL, DeMauro SB, Kirpalani H, Ziolkowski K, Hintz SR, Vohr BR, Watson V, Colaizy TT, Bell EF, Brumbaugh JE, Bann CM, Tan SM, Newman JE, Das A. The transfusion of prematures early school age follow-up (TOP 5): protocol for a longitudinal cohort study. BMC Pediatr. 2025 May 15;25(1):387. doi: 10.1186/s12887-025-05732-3.
Derived from this study: PubMed 38700862Salas AA, Gunn E, Carlo WA, Bell EF, Das A, Josephson CD, Patel RM, Tan S, Kirpalani H; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network. Timing of Red Blood Cell Transfusions and Occurrence of Necrotizing Enterocolitis: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2024 May 1;7(5):e249643. doi: 10.1001/jamanetworkopen.2024.9643.
Derived from this study: PubMed 37733345Chock VY, Kirpalani H, Bell EF, Tan S, Hintz SR, Ball MB, Smith E, Das A, Loggins YC, Sood BG, Chalak LF, Wyckoff MH, Kicklighter SD, Kennedy KA, Patel RM, Carlo WA, Johnson KJ, Watterberg KL, Sanchez PJ, Laptook AR, Seabrook RB, Cotten CM, Mancini T, Sokol GM, Ohls RK, Hibbs AM, Poindexter BB, Reynolds AM, DeMauro SB, Chawla S, Baserga M, Walsh MC, Higgins RD, Van Meurs KP; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Tissue Oxygenation Changes After Transfusion and Outcomes in Preterm Infants: A Secondary Near-Infrared Spectroscopy Study of the Transfusion of Prematures Randomized Clinical Trial (TOP NIRS). JAMA Netw Open. 2023 Sep 5;6(9):e2334889. doi: 10.1001/jamanetworkopen.2023.34889.
Derived from this study: PubMed 33382931Kirpalani H, Bell EF, Hintz SR, Tan S, Schmidt B, Chaudhary AS, Johnson KJ, Crawford MM, Newman JE, Vohr BR, Carlo WA, D'Angio CT, Kennedy KA, Ohls RK, Poindexter BB, Schibler K, Whyte RK, Widness JA, Zupancic JAF, Wyckoff MH, Truog WE, Walsh MC, Chock VY, Laptook AR, Sokol GM, Yoder BA, Patel RM, Cotten CM, Carmen MF, Devaskar U, Chawla S, Seabrook R, Higgins RD, Das A; Eunice Kennedy Shriver NICHD Neonatal Research Network. Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants. N Engl J Med. 2020 Dec 31;383(27):2639-2651. doi: 10.1056/NEJMoa2020248.
NICHD NRN WebsiteLink provided by the sponsor.
NICHD Pregnancy \& Perinatology BranchLink provided by the sponsor.
Individual participant dataSharing planned: Yes. NIH has had a long-standing policy to share and make available to the public the results and accomplishments of the activities that it funds. The NRN plans to share de-identified data after final publication in an NIH supported data repository such as the NICHD Data and Specimen Hub (https://dash.nichd.nih.gov)

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Michele C Walsh, MD principal investigator

Case Western Reserve University, Rainbow Babies and Children's Hospital

Abhik Das, PhD principal investigator

RTI International

Beena Sood, MD principal investigator

Wayne State University

20 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Death or Neurodevelopmental Impairment (time frame: Birth to 22-26 months corrected age). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01702805, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2025.