Transfusion of Prematures Trial - Full Text View

Purpose

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	Intervention	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

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label 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?

Resource links provided by NLM:

MedlinePlus related topics: Anemia Birth Weight Blood Transfusion and Donation Common Infant and Newborn Problems Uncommon Infant and Newborn Problems

U.S. FDA Resources

Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:

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.

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	1824
Study Start Date:	December 2012
Estimated Study Completion Date:	August 2017
Estimated Primary Completion Date:	August 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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: Liberal Cell Transfusion
Active Comparator: High Threshold Transfusion Transfusions will be administered using a higher threshold hemoglobin value.	Procedure: Restricted red cell transfusion

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	up to 48 Hours
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01702805

Contacts

Contact: Haresh M Kirpalani, MD	215-590-2455	kirpalanih@email.chop.edu
Contact: Rosemary Higgins, MD	(301) 435-7909	higginsr@mail.nih.gov

Locations

United States, Alabama
University of Alabama at Birmingham	Not yet recruiting
Birmingham, Alabama, United States, 35233
Contact: Waldemar A. Carlo, MD 205-934-4680 wcarlo@peds.uab.edu
Contact: Monica V. Collins, RN BSN (205) 934-5771 mcollins@peds.uab.edu
Principal Investigator: Waldemar A. Carlo, MD
United States, California
University of California - Los Angeles	Not yet recruiting
Los Angeles, California, United States, 90025
Contact: Uday Devaskar, MD 310-825-9357 udevaskar@mednet.ucla.edu
Contact: Teresa Chanlaw, BS (310) 794-4972 tchanlaw@mednet.ucla.edu
Principal Investigator: Uday Devaskar, MD
Stanford University	Not yet recruiting
Palo Alto, California, United States, 94304
Contact: Krisa P. Van Meurs, MD 650-723-5711 vanmeurs@leland.stanford.edu
Contact: M. Bethany Ball, BS CCRC (650) 725-8342 mbball@stanford.edu
Principal Investigator: Krisa P. Van Meurs, MD
United States, Georgia
Emory University	Not yet recruiting
Atlanta, Georgia, United States, 30303
Contact: Barbara J. Stoll, MD 404-727-5740 barbara_stoll@oz.ped.emory.edu
Contact: Ellen Hale, RN BS (404) 616-4218 ellen_hale@oz.ped.emory.edu
Principal Investigator: Barbara J. Stoll, MD
United States, Indiana
Indiana University	Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Brenda B. Poindexter, MD MS 317-274-3592 bpoindex@iupui.edu
Contact: Leslie D. Wilson, RN BSN (317) 274-8255 ldw@iupui.edu
Principal Investigator: Brenda B. Poindexter, MD MS
United States, Iowa
University of Iowa	Recruiting
Iowa City, Iowa, United States, 52242
Contact: Edward F. Bell, MD 319-356-4006 edward-bell@uiowa.edu
Contact: Karen J. Johnson, RN BSN (319) 356-2924 karen-johnson@uiowa.edu
Principal Investigator: Edward F. Bell, MD
United States, Michigan
Wayne State University	Not yet recruiting
Detroit, Michigan, United States, 48201
Contact: Seetha Shankaran, MD 313-580-4452 sshankar@med.wayne.edu
Contact: Rebecca Bara, RN BSN (313) 745-1436 rbara@med.wayne.edu
Principal Investigator: Seetha Shankaran, MD
United States, Missouri
Children's Mercy Hospital	Not yet recruiting
Kansas City, Missouri, United States, 64108
Contact: William Truog, MD 816-234-3592 wtruog@cmh.edu
Contact: Cheri Gauldin, BSN (816) 234-3920 cagauldin@cmh.edu
Principal Investigator: William Truog, MD
United States, New Mexico
University of New Mexico	Not yet recruiting
Albuquerque, New Mexico, United States, 87131
Contact: Kristi L. Watterberg, MD 505-272-3967 kwatterberg@salud.unm.edu
Contact: Conra Backstrom Lacy, RN (505) 272-0367 cbackstrom@salud.unm.edu
Principal Investigator: Kristi L. Watterberg, MD
United States, New York
University of Rochester	Recruiting
Rochester, New York, United States, 14642
Contact: Carl T D'Angio, MD 585-273-4911 carl_dangio@urmc.rochester.edu
Contact: Holly Wadkins 585-275-0218 Holly_Wadkins@urmc.rochester.edu
Principal Investigator: Carl T D'Angio, MD
United States, North Carolina
Duke University	Not yet recruiting
Durham, North Carolina, United States, 27710
Contact: Ronald N. Goldberg, MD 919-681-6025 goldb008@mc.duke.edu
Contact: Gloria Siaw, BSN CRA (919) 681-5859 gloria.siaw@duke.edu
Principal Investigator: Ronald N. Goldberg, MD
Sub-Investigator: C. Michael Cotten, MD MHS
RTI International	Active, not recruiting
Durham, North Carolina, United States, 27705
United States, Ohio
Cincinnati Children's Medical Center	Not yet recruiting
Cincinnati, Ohio, United States, 45267
Contact: Kurt Schibler, MD 513-636-3972 kurt.schibler@cchmc.org
Contact: Cathy Grisby, BSN CCRC (513) 558-4953 grisbyca@email.uc.edu
Principal Investigator: Kurt Schibler, MD
Case Western Reserve University, Rainbow Babies and Children's Hospital	Recruiting
Cleveland, Ohio, United States, 44106
Contact: Michele C. Walsh, MD MS 216-844-3759 mcw3@cwru.edu
Contact: Nancy S. Newman, BA RN (216) 368-3084 nxs5@cwru.edu
Principal Investigator: Michele C. Walsh, MD MS
Research Institute at Nationwide Children's Hospital	Not yet recruiting
Columbus, Ohio, United States, 43205
Contact: Leif Nelin, MD 614-722-3030 Leif.Nelin@nationwidechildrens.org
Contact: Christine Fortney, MS, RN 614-722-6489 christine.fortney@nationwidechildrens.org
Principal Investigator: Leif Nelin, MD
United States, Pennsylvania
Univeristy of Pennsylvania	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Barbara Schmidt, MD 215-662-3228 barbara.schmidt@uphs.upenn.edu
Contact: Aasma Chaudhary, BS 215-615-5442 aasma.chaudhary@uphs.upenn.edu
Principal Investigator: Barbara Schmidt, MD
United States, Rhode Island
Brown University, Women & Infants Hospital of Rhode Island	Recruiting
Providence, Rhode Island, United States, 02905
Contact: Abbot R. Laptook, MD 401-274-1122 alaptook@WIHRI.org
Contact: Angelita Hensman (401) 274-1122 ahensman@wihri.org
Principal Investigator: Abbot R. Laptook, MD
United States, Texas
University of Texas Southwestern Medical Center at Dallas	Not yet recruiting
Dallas, Texas, United States, 75235
Contact: Pablo J. Sanchez, MD 214-648-3753 Pablo.Sanchez@UTSouthwestern.edu
Contact: Diana M. Vasil, RNC-NIC (214) 648-3789 Diana.Vasil@utsouthwestern.edu
Principal Investigator: Pablo J. Sanchez, MD
University of Texas Health Science Center at Houston	Not yet recruiting
Houston, Texas, United States, 77030
Contact: Kathleen A. Kennedy, MD MPH 713-500-6708 Kathleen.A.Kennedy@uth.tmc.edu
Contact: Georgia E. McDavid, RN (713) 500-5734 Georgia.E.McDavid@uth.tmc.edu
Principal Investigator: Kathleen A. Kennedy, MD MPH
Sub-Investigator: Jon E. Tyson, MD MPH

Sponsors and Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

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

More Information

Additional Information:

NICHD NRN Website This link exits the ClinicalTrials.gov site

NICHD Pregnancy & Perinatology Branch This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:	NCT01702805 History of Changes
Other Study ID Numbers:	NICHD-NRN-0048, U01HL112776, U01HL112748
Study First Received:	August 30, 2012
Last Updated:	February 13, 2013
Health Authority:	United States: Federal Government United States: Institutional Review Board

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

NICHD Neonatal Research Network
Very Low Birth Weight (VLBW)
Extremely Low Birth Weight (ELBW)
Transfusions

Additional relevant MeSH terms:

Anemia
Birth Weight
Bronchopulmonary Dysplasia
Infant, Newborn, Diseases
Hematologic Diseases
Body Weight

Signs and Symptoms
Ventilator-Induced Lung Injury
Lung Injury
Lung Diseases
Respiratory Tract Diseases
Infant, Premature, Diseases

ClinicalTrials.gov processed this record on May 23, 2013

Transfusion of Prematures Trial (TOP)