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Transfusion of Prematures Trial (TOP)

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ClinicalTrials.gov Identifier: NCT01702805
Recruitment Status : Active, not recruiting
First Posted : October 8, 2012
Last Update Posted : March 11, 2019
Sponsor:
Collaborators:
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

Tracking Information
First Submitted Date  ICMJE August 30, 2012
First Posted Date  ICMJE October 8, 2012
Last Update Posted Date March 11, 2019
Actual Study Start Date  ICMJE December 2012
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 5, 2012)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01702805 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 5, 2012)
  • Grade 3 or 4 IVH, cystic PVL, or ventriculomegaly [ Time Frame: Birth to 36 weeks PMA ]
  • Moderate or severe cerebral palsy [ Time Frame: Birth to 26 months corrected age ]
  • Episodes of necrotizing enterocolitis [ Time Frame: Birth to 36 weeks PMA ]
    Episodes of NEC Bell stage II or higher.
  • Time to full feeds [ Time Frame: Birth to 36 weeks PMA ]
    The amount of time it takes for infant to achieve full feeds.
  • Length of hospital stay [ Time Frame: Birth to 36 weeks PMA ]
  • Number of transfusions [ Time Frame: Birth to 36 weeks PMA ]
    Number of transfusions, numbers of donor exposures by RBC donors or other blood product
  • Age at final tracheal extubation [ Time Frame: Birth to 36 weeks PMA ]
  • Age at final caffeine dose [ Time Frame: Birth to 36 weeks PMA ]
  • Growth [ Time Frame: Birth to 36 weeks PMA ]
    Weight, length, and head circumference at 36 weeks postmenstrual age
  • 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).
  • Respiratory disease [ Time Frame: Birth to 26 months corrected age ]
    The presence of respiratory disease necessitating readmission before 22-26 months follow-up.
  • Hydrocephalus shunt, microcephaly, or seizure disorder [ Time Frame: Birth to 26 months corrected age ]
  • Economic cost-benefit analysis [ Time Frame: Birth to 26 months corrected age ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Transfusion of Prematures Trial
Official Title  ICMJE 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?
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Infant, Newborn, Diseases
  • Infant, Extremely Low Birth Weight
  • Infant, Small for Gestational Age
  • Bronchopulmonary Dysplasia (BPD)
  • Anemia
Intervention  ICMJE
  • Procedure: Liberal Cell Transfusion
  • Procedure: Restricted red cell transfusion
Study Arms  ICMJE
  • 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
    Intervention: Procedure: Restricted red cell transfusion
  • Active Comparator: High Threshold Transfusion
    Transfusions will be administered using a higher threshold hemoglobin value.
    Intervention: Procedure: Liberal Cell Transfusion
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: October 5, 2012)
1824
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2019
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 48 Hours   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01702805
Other Study ID Numbers  ICMJE NICHD-NRN-0050
U01HL112776 ( U.S. NIH Grant/Contract )
U01HL112748 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
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 (https://dash.nichd.nih.gov)
Responsible Party NICHD Neonatal Research Network
Study Sponsor  ICMJE NICHD Neonatal Research Network
Collaborators  ICMJE
  • National Heart, Lung, and Blood Institute (NHLBI)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators  ICMJE
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
PRS Account NICHD Neonatal Research Network
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP