Transfusion of Prematures Trial (TOP)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT01702805
First received: August 30, 2012
Last updated: March 19, 2014
Last verified: February 2014

August 30, 2012
March 19, 2014
December 2012
August 2015   (final data collection date for primary outcome measure)
Death or significant neurodevelopmental impairment [ Time Frame: Birth to 22-26 months corrected gestational age ] [ Designated as safety issue: Yes ]
Number of children surviving without significant neurodevelopmental impairment at 22-26 months of corrected age.
Same as current
Complete list of historical versions of study NCT01702805 on ClinicalTrials.gov Archive Site
  • Grade 3 or 4 IVH, cystic PVL, or ventriculomegaly [ Time Frame: Birth to 36 weeks PMA ] [ Designated as safety issue: Yes ]
  • Moderate or severe cerebral palsy [ Time Frame: Birth to 26 months corrected age ] [ Designated as safety issue: Yes ]
  • Episodes of necrotizing enterocolitis [ Time Frame: Birth to 36 weeks PMA ] [ Designated as safety issue: Yes ]
    Episodes of NEC Bell stage II or higher.
  • Time to full feeds [ Time Frame: Birth to 36 weeks PMA ] [ Designated as safety issue: Yes ]
    The amount of time it takes for infant to achieve full feeds.
  • Length of hospital stay [ Time Frame: Birth to 36 weeks PMA ] [ Designated as safety issue: Yes ]
  • Number of transfusions [ Time Frame: Birth to 36 weeks PMA ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
  • Age at final caffeine dose [ Time Frame: Birth to 36 weeks PMA ] [ Designated as safety issue: Yes ]
  • Growth [ Time Frame: Birth to 36 weeks PMA ] [ Designated as safety issue: Yes ]
    Weight, length, and head circumference at 36 weeks postmenstrual age
  • Survival to discharge without severe morbidity [ Time Frame: Birth to 36 weeks PMA ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
  • Economic cost-benefit analysis [ Time Frame: Birth to 26 months corrected age ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Transfusion of Prematures Trial
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?

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.

Long-term outcomes of extremely low birth weight (ELBW) preterm infants, those weighing less than 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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
1824
August 2017
August 2015   (final data collection date for primary outcome measure)

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.
Both
up to 48 Hours
No
Contact: Haresh M Kirpalani, MD 215-590-1653
Contact: Rosemary Higgins, MD (301) 435-5575
United States
 
NCT01702805
NICHD-NRN-0050, U01HL112776, U01HL112748
Yes
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Heart, Lung, and Blood Institute (NHLBI)
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: Ron N Goldberg, MD Duke University
Principal Investigator: Barbara J Stoll, MD Emory University
Principal Investigator: Brenda B Poindexter, MD, MS Indiana University
Principal Investigator: Krisa P Van Meurs, MD Stanford University
Principal Investigator: Kurt Schibler, MD Cincinnati Children's Medical Center
Principal Investigator: Waldemar A Carlo, MD University of Alabama at Birmingham
Principal Investigator: Kristi L Watterberg, MD University of New Mexico
Principal Investigator: Pablo J Sanchez, 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: Leif Nelin, MD Research Institute at Nationwide Children's Hospital
Principal Investigator: William Truog, MD Children's Mercy Hospital-Kansas City, MO
Principal Investigator: Uday Devaskar, MD University of California, Los Angeles
Study Director: Haresh M Kirpalani, MD University of Pennsylvania
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
February 2014

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