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Transfusion of Prematures Trial (TOP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01702805
Recruitment Status : Active, not recruiting
First Posted : October 8, 2012
Last Update Posted : February 5, 2020
National Heart, Lung, and Blood Institute (NHLBI)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
NICHD Neonatal Research Network

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.

Condition or disease Intervention/treatment Phase
Infant, Newborn, Diseases Infant, Extremely Low Birth Weight Infant, Small for Gestational Age Bronchopulmonary Dysplasia (BPD) Anemia Procedure: Liberal Cell Transfusion Procedure: Restricted red cell transfusion Phase 3

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 < 29 weeks GA 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.

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1824 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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?
Actual Study Start Date : December 2012
Actual Primary Completion Date : January 2020
Estimated Study Completion Date : August 2023

Arm Intervention/treatment
Active Comparator: 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
Procedure: Restricted red cell transfusion
Active Comparator: High Threshold Transfusion
Transfusions will be administered using a higher threshold hemoglobin value.
Procedure: Liberal Cell Transfusion

Primary Outcome Measures :
  1. Death or significant neurodevelopmental impairment [ Time Frame: Birth to 22-26 months corrected gestational age ]
    Number of children surviving without significant neurodevelopmental impairment at 22-26 months of corrected age.

Secondary Outcome Measures :
  1. Grade 3 or 4 IVH, cystic PVL, or ventriculomegaly [ Time Frame: Birth to 36 weeks PMA ]
  2. Moderate or severe cerebral palsy [ Time Frame: Birth to 26 months corrected age ]
  3. Episodes of necrotizing enterocolitis [ Time Frame: Birth to 36 weeks PMA ]
    Episodes of NEC Bell stage II or higher.

  4. Time to full feeds [ Time Frame: Birth to 36 weeks PMA ]
    The amount of time it takes for infant to achieve full feeds.

  5. Length of hospital stay [ Time Frame: Birth to 36 weeks PMA ]
  6. Number of transfusions [ Time Frame: Birth to 36 weeks PMA ]
    Number of transfusions, numbers of donor exposures by RBC donors or other blood product

  7. Age at final tracheal extubation [ Time Frame: Birth to 36 weeks PMA ]
  8. Age at final caffeine dose [ Time Frame: Birth to 36 weeks PMA ]
  9. Growth [ Time Frame: Birth to 36 weeks PMA ]
    Weight, length, and head circumference at 36 weeks postmenstrual age

  10. Survival to discharge without severe morbidity [ Time Frame: Birth to 36 weeks PMA ]
    Survival to discharge without severe morbidity, defined as any of the following: bronchopulmonary dysplasia, retinopathy of prematurity (stage >3 or requiring treatment), or serious brain abnormality (grade 3 or 4 intraventricular hemorrhage, periventricular leukomalacia, or ventriculomegaly).

  11. Respiratory disease [ Time Frame: Birth to 26 months corrected age ]
    The presence of respiratory disease necessitating readmission before 22-26 months follow-up.

  12. Hydrocephalus shunt, microcephaly, or seizure disorder [ Time Frame: Birth to 26 months corrected age ]
  13. Economic cost-benefit analysis [ Time Frame: Birth to 26 months corrected age ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   up to 48 Hours   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Birth weight less than 1000 grams.
  • Gestational age at least 22 weeks but less than 29 completed 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
  • High probability that the family is socially disorganized to the point of being unable to attend follow-up at 22-26 months.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01702805

Show Show 20 study locations
Sponsors and Collaborators
NICHD Neonatal Research Network
National Heart, Lung, and Blood Institute (NHLBI)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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Principal Investigator: 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
Study Director: Haresh M Kirpalani, MD University of Pennsylvania
Principal Investigator: Bradley Yoder, MD University of Utah
Additional Information:
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Responsible Party: NICHD Neonatal Research Network Identifier: NCT01702805    
Other Study ID Numbers: NICHD-NRN-0050
U01HL112776 ( U.S. NIH Grant/Contract )
U01HL112748 ( U.S. NIH Grant/Contract )
First Posted: October 8, 2012    Key Record Dates
Last Update Posted: February 5, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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 (
Keywords provided by NICHD Neonatal Research Network:
NICHD Neonatal Research Network
Very Low Birth Weight (VLBW)
Extremely Low Birth Weight (ELBW)
Additional relevant MeSH terms:
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Bronchopulmonary Dysplasia
Infant, Newborn, Diseases
Birth Weight
Body Weight
Signs and Symptoms
Ventilator-Induced Lung Injury
Lung Injury
Lung Diseases
Respiratory Tract Diseases
Infant, Premature, Diseases