Transfusion of Prematures Trial (TOP)
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| ClinicalTrials.gov Identifier: NCT01702805 |
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Recruitment Status :
Active, not recruiting
First Posted : October 8, 2012
Last Update Posted : August 12, 2020
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| 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 gestational age at least 22 weeks but less than 29 weeks 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.
A secondary study entitled "Economic Evaluation Ancillary to the Transfusion of Prematures Randomized Controlled Trial" will determine whether higher transfusion threshold will result in lower total costs to society over the first 22 to 26 corrected months of life and estimate the incremental cost-effectiveness ratio for survival without neurodevelopmental impairment, from the perspective of society, the third-party payer, and the family.
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 |
| 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 |
|---|---|
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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
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Procedure: Restricted red cell transfusion |
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Active Comparator: High Threshold Transfusion
Transfusions will be administered using a higher threshold hemoglobin value.
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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 defined as one or more of the following: cognitive delay (BSID-III Cognitive score < 85), moderate or severe cerebral palsy, or severe visual or hearing impairment at 22-26 months of corrected age
- Survival to discharge without severe morbidity [ Time Frame: Birth to the earliest of hospital discharge to home, 120 days in hospital, transfer to another facility or death ]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).
- Length [ Time Frame: Birth to 36 weeks PMA ]Z-score for length at 36 weeks postmenstrual age or at discharge from NICU, whichever occurs first based on Olsen growth curves (Olsen IE, Groveman SA, Lawson ML, Clark RH, and Zemel BS. New intrauterine growth curves based on United States data. Pediatrics 2010; 125(2):e214-e224).
- Weight [ Time Frame: Birth to 36 weeks PMA ]Z-score for weight at 36 weeks postmenstrual age or at discharge from NICU, whichever occurs first based on Olsen growth curves (Olsen IE, Groveman SA, Lawson ML, Clark RH, and Zemel BS. New intrauterine growth curves based on United States data. Pediatrics 2010; 125(2):e214-e224).
- Head Circumference [ Time Frame: Birth to 36 weeks PMA ]Z-score for head circumference at 36 weeks postmenstrual age or at discharge from NICU, whichever occurs first based on Olsen growth curves (Olsen IE, Groveman SA, Lawson ML, Clark RH, and Zemel BS. New intrauterine growth curves based on United States data. Pediatrics 2010; 125(2):e214-e224).
- Grade 3 or 4 intraventricular hemorrhage, periventricular leukomalacia, or ventriculomegaly [ Time Frame: Birth to the earliest of hospital discharge to home, 120 days in hospital, transfer to another facility or death ]Serious abnormality on cranial ultrasound examination
- Age at final tracheal extubation [ Time Frame: Birth to 36 weeks PMA ]
- Age at final caffeine dose [ Time Frame: Birth to 36 weeks PMA ]
- Number of transfusions [ Time Frame: Birth to 36 weeks PMA ]Ever received any transfusion
- Numbers of donor exposures [ Time Frame: Birth to 36 weeks PMA ]Numbers of donor exposures by RBC donors or other blood product
- Length of hospital stay [ Time Frame: Birth to the earliest of hospital discharge to home, 120 days in hospital, transfer to another facility or death ]Length of hospital stay in the level 3 NICU referral site, or in the level 3 area of the referral site
- Necrotizing Enterocolitis [ Time Frame: Birth to the earliest of hospital discharge to home, 120 days in hospital, transfer to another facility or death ]Episodes of necrotizing enterocolitis of Bell stage 2 or higher
- Bronchopulmonary Dysplasia [ Time Frame: Birth to 36 weeks PMA ]
- Retinopathy of Prematurity [ Time Frame: Birth to the earliest of hospital discharge to home, 120 days in hospital, transfer to another facility or death ]Stage >3 or requiring treatment
- Cerebral Palsy [ Time Frame: Birth to 22-26 months corrected gestational age ]The incidence of ambulatory and non-ambulatory CP defined by GMFCS
- Hydrocephalus shunt, microcephaly, or seizure disorder [ Time Frame: Birth to 22-26 months corrected gestational age ]
- Respiratory disease [ Time Frame: Birth to 22-26 months corrected gestational age ]The presence of respiratory disease necessitating readmission before 22-26 months follow-up.
- BSID III cognitive, language and motor scores [ Time Frame: Birth to 22-26 months corrected gestational age ]Including cognitive outcomes at 1 SD cut-off on the BSID III standardized scales and BSID III cognitive, language and motor scores at 2 SD cut-offs (<70).
- Economic cost-benefit analysis [ Time Frame: Birth to 22-26 months corrected gestational age ]
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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 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
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
- 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.
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
Show 20 study locations
| 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 |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | NICHD Neonatal Research Network |
| ClinicalTrials.gov 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: | August 12, 2020 |
| Last Verified: | August 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 (https://dash.nichd.nih.gov) |
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NICHD Neonatal Research Network Very Low Birth Weight (VLBW) Extremely Low Birth Weight (ELBW) Transfusions |
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Bronchopulmonary Dysplasia Infant, Newborn, Diseases Birth Weight Body Weight Ventilator-Induced Lung Injury |
Lung Injury Lung Diseases Respiratory Tract Diseases Infant, Premature, Diseases |