Transfusion of Prematures Trial

NCT01702805 | Completed Results DMC

• 3 other identifiers: NICHD-NRN-0050U01HL112776U01HL112748
• Study Type: interventional
• Target: 1,824
• Locations: 1 country
• Sites: 20

Brief 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.

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

Outcome Measures

Primary Outcomes (7)

• Death or Neurodevelopmental Impairment

  A composite outcome that measures the occurrence of death or neurodevelomental impairment between birth and 22-26 months corrected age.

  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.

  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.

  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.

  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.

  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.

  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.

  at 22-26 months corrected age

Secondary Outcomes (23)

• Survival to Discharge Without Severe Complications

  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

  at 36 weeks postmenstrual 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)

• Necrotizing Enterocolitis, Bell's Stage >=2

  Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)

Study Arms (2)

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

Procedure: Restricted red cell transfusion

High Threshold Transfusion

ACTIVE COMPARATOR

Transfusions will be administered using a higher threshold hemoglobin value.

Procedure: Liberal Cell Transfusion

Interventions

Liberal Cell Transfusion PROCEDURE

High Threshold Transfusion

Restricted red cell transfusion PROCEDURE

Low Threshold Transfusion

Eligibility Criteria

• Age: Up to 48 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• NICHD Neonatal Research Network: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (20)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

University of California - Los Angeles

Los Angeles, California, 90025, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Emory University

Atlanta, Georgia, 30303, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

RTI International

Durham, North Carolina, 27705, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Medical Center

Cincinnati, Ohio, 45267, United States

Location

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

Cleveland, Ohio, 44106, United States

Location

Research Institute at Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Univeristy of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Brown University, Women & Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75235, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Related Publications (4)

• 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.

  PMID: 40375228 DERIVED

• 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.

  PMID: 38700862 DERIVED

• 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.

  PMID: 37733345 DERIVED

• 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.

  PMID: 33382931 DERIVED

Related Links

• NICHD NRN Website
• NICHD Pregnancy \& Perinatology Branch

MeSH Terms

Conditions

Infant, Newborn, Diseases; Bronchopulmonary Dysplasia; Anemia

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Haresh Kirpalani
• Organization: Emeritus Professor U Pennsylvania at CHOP and Emeritus Professor McMaster University, Dept Pediatrics

kirpalan@mcmaster.ca

267-844-3233

Study Officials

• Michele C Walsh, MD

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

  PRINCIPAL INVESTIGATOR

• Abhik Das, PhD

  RTI International

  PRINCIPAL INVESTIGATOR

• Beena Sood, MD

  Wayne State University

  PRINCIPAL INVESTIGATOR

• Abbot R Laptook, MD

  Brown University, Women & Infants Hospital of Rhode Island

  PRINCIPAL INVESTIGATOR

• Michael Cotten, MD

  Duke University

  PRINCIPAL INVESTIGATOR

• Ravi Patel, MD

  Emory University

  PRINCIPAL INVESTIGATOR

• Greg Sokol, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

• Krisa P Van Meurs, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Brenda Poindexter, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

• Waldemar A Carlo, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• Kristi L Watterberg, MD

  University of New Mexico

  PRINCIPAL INVESTIGATOR

• Myra Wyckoff, MD

  University of Texas, Southwestern Medical Center at Dallas

  PRINCIPAL INVESTIGATOR

• Kathleen A Kennedy, MD, MPH

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

• Carl T D'Angio, MD

  University of Rochester

  PRINCIPAL INVESTIGATOR

• Pablo Sanchez, MD

  Research Institute at Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

• William Truog, MD

  Children's Mercy Hospital Kansas City

  PRINCIPAL INVESTIGATOR

• Uday Devaskar, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

• Haresh M Kirpalani, MD

  University of Pennsylvania

  STUDY DIRECTOR

• Bradley Yoder, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2012
• First Posted: October 8, 2012
• Study Start: December 1, 2012
• Primary Completion: January 1, 2020
• Study Completion: April 29, 2025
• Last Updated: November 14, 2025
• Results First Posted: February 11, 2022

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

US (20)