Trial of Aggressive Versus Conservative Phototherapy in Infants <1,000 Grams Birth Weight

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00114543
First received: June 15, 2005
Last updated: January 9, 2011
Last verified: September 2010
  Purpose

This multi-center, randomized clinical trial compared different bilirubin levels as thresholds for timing of phototherapy in extremely low birth weight infants. The primary hypothesis was that there would be no difference in death or neurodevelopmental impairment at 18-22 months corrected age in infants treated by either aggressive or conservative threshold limits. 1,978 infants were enrolled.


Condition Intervention Phase
Hyperbilirubinemia, Neonatal
Jaundice, Neonatal
Infant, Newborn
Infant, Low Birth Weight
Infant, Small for Gestational Age
Infant, Premature
Procedure: Aggressive Phototherapy 501-750g
Procedure: Aggressive Phototherapy 751-1000g
Procedure: Conservative Phototherapy 501-750g
Procedure: Conservative Phototherapy 751-1000g
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Trial of Aggressive or Conservative Phototherapy for Extremely Low Birth Weight Infants

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Death or neurodevelopmental impairment (MDI <70; PDI <70; cerebral palsy; blindness; or severe hearing loss) [ Time Frame: 0-22 months corrected age ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Patent ductus arteriosus requiring drug or surgical treatment [ Time Frame: 36 weeks post conceptual age ] [ Designated as safety issue: Yes ]
  • Retinopathy of prematurity [ Time Frame: 36 weeks post conceptual age ] [ Designated as safety issue: Yes ]
  • Bronchopulmonary dysplasia (BPD) [ Time Frame: 36 weeks post conceptual age ] [ Designated as safety issue: Yes ]
  • Ventilator settings and FiO2 at 36 weeks [ Time Frame: 36 weeks post conceptual age ] [ Designated as safety issue: Yes ]
  • Necrotizing enterocolitis (NEC) [ Time Frame: 120 days old or at discharge ] [ Designated as safety issue: Yes ]
  • Intraventricular hemorrhage (IVH) by grade [ Time Frame: 120 days old or at discharge ] [ Designated as safety issue: Yes ]
  • Periventricular leukomalacia [ Time Frame: 120 days old or at discharge ] [ Designated as safety issue: Yes ]
  • Sepsis [ Time Frame: 120 days old or at discharge ] [ Designated as safety issue: Yes ]
  • Hearing assessments [ Time Frame: 120 days old or at discharge ] [ Designated as safety issue: Yes ]

Enrollment: 1974
Study Start Date: September 2002
Study Completion Date: November 2007
Primary Completion Date: April 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Aggressive ELBW
In Aggressive group 1, infants with birth weights 501-750g.
Procedure: Aggressive Phototherapy 501-750g
Phototherapy started, stopped, and/or restarted when total serum bilirubin levels reach 5 mg/dl during days of life 1-14.
Active Comparator: Aggressive VLBW
In the Aggressive group 2, infants with birth weights 751-1000g.
Procedure: Aggressive Phototherapy 751-1000g
Phototherapy started, stopped, and/or restarted when total serum bilirubin levels reach 5 mg/dl during days of life 1-7, and started, stopped, and/or restarted when levels reach 7 mg/dl during days of life 8-14.
Active Comparator: Conservative ELBW
In the Conservative group 1, infants with birth weights 501-750g.
Procedure: Conservative Phototherapy 501-750g
Phototherapy started, stopped, and/or restarted when total serum bilirubin levels reach ≥8.0 mg/dl during days of life 1-14.
Active Comparator: Conservative VLBW
In the Conservative group 2, infants with birth weights 751-1000g.
Procedure: Conservative Phototherapy 751-1000g
Phototherapy started, stopped, and/or restarted when total serum bilirubin levels reach ≥10.0 mg/dl during days of life 1-14.

Detailed Description:

In NICHD Neonatal Research Network (NRN) centers in 2002, phototherapy was administered to 94 percent of the extremely low birth weight (ELBW) infants who survive more than 12 hours. Yet, it is unclear what level of bilirubin in the blood is harmful for these very tiny infants -- no data existed from large or recent clinical trials to define the risks, benefits, and appropriate indications for phototherapy in these infants. The largest and most recent trial was the NICHD Collaborative Phototherapy Trial which involved infants treated in 1974-1976 and included only 77 ELBW infants. Data from this study and others suggested that phototherapy could have important hazards as well as benefits for ELBW infants.

This NRN study used two different bilirubin levels as thresholds for timing of phototherapy in 1,978 extremely low birth weight infants, examining the primary hypothesis that there would be no difference in death or neurodevelopmental impairment at 18-22 months corrected age between the aggressively and conservatively treated groups.

Enrolled infants were stratified by birth weight (501-750g and 751-1,000g) and randomized to receive phototherapy regimens based on either an aggressive threshold or a conservative threshold of total serum bilirubin.

In the Aggressive group:

  • 501-750 grams birth weight infants, phototherapy was started, stopped, and restarted based on a total serum bilirubin threshold level of 5 mg/dl for day of life 1-14.
  • 751-1,000 grams birth weight infants, phototherapy was started, stopped, and restarted based on a total serum bilirubin threshold level of 5 mg/dl for day of life 1-7 and 7 mg/dl for day of life 8-14.

In the Conservative group:

  • 501-750 grams birth weight infants, phototherapy was started, stopped, and restarted based on a total serum bilirubin threshold level of 8 mg/dl for day of life 1-14.
  • 751-1,000 grams birth weight infants, phototherapy was started, stopped, and restarted based on a total serum bilirubin threshold level of 10 mg/dl for day of life 1-14.

The phototherapy regimens are designed to fall within the range of clinical practice and to assure a sizable difference between groups in total serum bilirubin levels and duration of phototherapy.

The primary outcome was death or neurodevelopmental impairment at 18-22 months corrected age determined at an outpatient clinic visit. Secondary outcomes included death, abnormal neurodevelopmental outcome, severe hearing loss, cerebral palsy, blindness, and important medical outcomes.

  Eligibility

Ages Eligible for Study:   up to 36 Hours
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • 501-1000 grams birth weight
  • 12-36 hours postnatal age

Exclusion criteria:

  • Terminal condition (pH <6.8 for >2 hours OR persistent bradycardia, heart rate <100 bpm, associated with hypoxia for >2 hours]
  • Prior use of phototherapy
  • Major congenital anomaly
  • Hydrops fetalis or severe hemolytic disease diagnosed in-utero
  • Overt congenital nonbacterial infection
  • Parental refusal or inability to provide consent
  • Attending physician refusal
  • Parents who are considered unlikely to return for follow-up evaluation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00114543

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, California
Stanford University
Palo Alto, California, United States, 94304
University of California at San Diego
San Diego, California, United States, 92103-8774
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06504
United States, Florida
University of Miami
Miami, Florida, United States, 33136
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30303
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48201
United States, New York
University of Rochester
Rochester, New York, United States, 14642
United States, North Carolina
Wake Forest University
Charlotte, North Carolina, United States, 27157
Duke University
Durham, North Carolina, United States, 27710
RTI International
Durham, North Carolina, United States, 27705
United States, Ohio
Cincinnati Children's Medical Center
Cincinnati, Ohio, United States, 45267
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106
United States, Rhode Island
Brown University, Women & Infants Hospital of Rhode Island
Providence, Rhode Island, United States, 02905
United States, Texas
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75235
University of Texas Health Science Center at Houston
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: Abbot R. Laptook, MD Brown University, Women & Infants Hospital of Rhode Island
Principal Investigator: Michele C. Walsh, MD MS Case Western Reserve University, Rainbow Babies and Children's Hospital
Principal Investigator: Ronald N. Goldberg, MD Duke University
Principal Investigator: Brenda B. Poindexter, MD MS Indiana University
Principal Investigator: Abhik Das, PhD RTI International
Principal Investigator: Ronnie Guillet, MD PhD University of Rochester
Principal Investigator: Pablo J. Sanchez, MD University of Texas Southwestern Medical Center at Dallas
Principal Investigator: Barbara J. Stoll, MD Emory University
Principal Investigator: Krisa P. Van Meurs, MD Stanford University
Principal Investigator: Neil N. Finer, MD University of California, San Diego
Principal Investigator: Kurt Schibler, MD Cincinnati Children's Medical Center
Principal Investigator: Waldemar A. Carlo, MD University of Alabama at Birmingham
Principal Investigator: Brenda H. Morris, MD The University of Texas Health Science Center, Houston
Principal Investigator: Seetha Shankaran, MD Wayne State University
Principal Investigator: Richard A. Ehrenkranz, MD Yale University
Principal Investigator: Shahnaz Duara, MD University of Miami
Principal Investigator: T. Michael O`Shea, MD MPH Wake Forest School of Medicine
  More Information

Additional Information:
Publications:

Responsible Party: Brenda H. Morris, Lead Principal Investigator, University of Texas Health Science Center at Houston
ClinicalTrials.gov Identifier: NCT00114543     History of Changes
Other Study ID Numbers: NICHD-NRN-0029, M01RR016587, M01RR000030, M01RR000032, M01RR000039, M01RR000044, M01RR006022, M01RR000633, M01RR000070, M01RR007122, M01RR000750, M01RR000080, M01RR008084, U01HD036790, U10HD021364, U10HD021373, U10HD021385, U10HD021397, U10HD027851, U10HD027853, U10HD027856, U10HD027871, U10HD027880, U10HD027904, U10HD034216, U10HD040461, U10HD040492, U10HD040498, U10HD040521, U10HD040689
Study First Received: June 15, 2005
Last Updated: January 9, 2011
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
Bilirubin
Phototherapy
Very Low Birth Weight (VLBW)
Extremely Low Birth Weight (ELBW)
Prematurity
Neurodevelopmental outcome

Additional relevant MeSH terms:
Birth Weight
Hyperbilirubinemia
Jaundice
Jaundice, Neonatal
Hyperbilirubinemia, Neonatal
Body Weight
Signs and Symptoms
Pathologic Processes
Skin Manifestations
Infant, Newborn, Diseases

ClinicalTrials.gov processed this record on July 29, 2014