Study Results
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View full resultsBasic Information
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COMPLETED
NA
1824 participants
INTERVENTIONAL
2012-12-31
2025-04-29
Brief Summary
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Detailed Description
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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
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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Low Threshold Transfusion
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
Restricted red cell transfusion
High Threshold Transfusion
Transfusions will be administered using a higher threshold hemoglobin value.
Liberal Cell Transfusion
Interventions
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Liberal Cell Transfusion
Restricted red cell transfusion
Eligibility Criteria
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Inclusion Criteria
* Gestational age at least 22 weeks but less than 29 weeks
* Admitted to the NICU within 48 hours of life
Exclusion Criteria
* 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.
48 Hours
ALL
No
Sponsors
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National Heart, Lung, and Blood Institute (NHLBI)
NIH
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
NIH
NICHD Neonatal Research Network
NETWORK
Responsible Party
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Principal Investigators
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Michele C Walsh, MD
Role: PRINCIPAL_INVESTIGATOR
Case Western Reserve University, Rainbow Babies and Children's Hospital
Abhik Das, PhD
Role: PRINCIPAL_INVESTIGATOR
RTI International
Beena Sood, MD
Role: PRINCIPAL_INVESTIGATOR
Wayne State University
Abbot R Laptook, MD
Role: PRINCIPAL_INVESTIGATOR
Brown University, Women & Infants Hospital of Rhode Island
Michael Cotten, MD
Role: PRINCIPAL_INVESTIGATOR
Duke University
Ravi Patel, MD
Role: PRINCIPAL_INVESTIGATOR
Emory University
Greg Sokol, MD
Role: PRINCIPAL_INVESTIGATOR
Indiana University
Krisa P Van Meurs, MD
Role: PRINCIPAL_INVESTIGATOR
Stanford University
Brenda Poindexter, MD
Role: PRINCIPAL_INVESTIGATOR
Children's Hospital Medical Center, Cincinnati
Waldemar A Carlo, MD
Role: PRINCIPAL_INVESTIGATOR
University of Alabama at Birmingham
Kristi L Watterberg, MD
Role: PRINCIPAL_INVESTIGATOR
University of New Mexico
Myra Wyckoff, MD
Role: PRINCIPAL_INVESTIGATOR
University of Texas, Southwestern Medical Center at Dallas
Kathleen A Kennedy, MD, MPH
Role: PRINCIPAL_INVESTIGATOR
The University of Texas Health Science Center, Houston
Carl T D'Angio, MD
Role: PRINCIPAL_INVESTIGATOR
University of Rochester
Pablo Sanchez, MD
Role: PRINCIPAL_INVESTIGATOR
Research Institute at Nationwide Children's Hospital
William Truog, MD
Role: PRINCIPAL_INVESTIGATOR
Children's Mercy Hospital Kansas City
Uday Devaskar, MD
Role: PRINCIPAL_INVESTIGATOR
University of California, Los Angeles
Haresh M Kirpalani, MD
Role: STUDY_DIRECTOR
University of Pennsylvania
Bradley Yoder, MD
Role: PRINCIPAL_INVESTIGATOR
University of Utah
Locations
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University of Alabama at Birmingham
Birmingham, Alabama, United States
University of California - Los Angeles
Los Angeles, California, United States
Stanford University
Palo Alto, California, United States
Emory University
Atlanta, Georgia, United States
Indiana University
Indianapolis, Indiana, United States
University of Iowa
Iowa City, Iowa, United States
Wayne State University
Detroit, Michigan, United States
Children's Mercy Hospital
Kansas City, Missouri, United States
University of New Mexico
Albuquerque, New Mexico, United States
University of Rochester
Rochester, New York, United States
RTI International
Durham, North Carolina, United States
Duke University
Durham, North Carolina, United States
Cincinnati Children's Medical Center
Cincinnati, Ohio, United States
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States
Research Institute at Nationwide Children's Hospital
Columbus, Ohio, United States
Univeristy of Pennsylvania
Philadelphia, Pennsylvania, United States
Brown University, Women & Infants Hospital of Rhode Island
Providence, Rhode Island, United States
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States
University of Texas Health Science Center at Houston
Houston, Texas, United States
University of Utah
Salt Lake City, Utah, United States
Countries
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References
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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.
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.
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.
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.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Related Links
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NICHD NRN Website
NICHD Pregnancy \& Perinatology Branch
Other Identifiers
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