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 : February 5, 2020
|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|
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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||1824 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
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
- 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.
- 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 ]
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 ClinicalTrials.gov identifier (NCT number): NCT01702805
|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|