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

NCT00114543 | Completed Phase 3 DMC

• 30 other identifiers: NICHD-NRN-0029M01RR016587M01RR000030M01RR000032M01RR000039M01RR000044M01RR006022M01RR000633M01RR000070M01RR007122M01RR000750M01RR000080M01RR008084U01HD036790U10HD021364U10HD021373U10HD021385U10HD021397U10HD027851U10HD027853U10HD027856U10HD027871U10HD027880U10HD027904U10HD034216U10HD040461U10HD040492U10HD040498U10HD040521U10HD040689
• Study Type: interventional
• Target: 1,974
• Locations: 1 country
• Sites: 17

Brief Summary

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.

Conditions

Hyperbilirubinemia, Neonatal; Jaundice, Neonatal; Infant, Newborn; Infant, Low Birth Weight; Infant, Small for Gestational Age; Infant, Premature

Keywords

NICHD Neonatal Research Network; Bilirubin; Phototherapy; Very Low Birth Weight (VLBW); Extremely Low Birth Weight (ELBW); Prematurity; Neurodevelopmental outcome

Outcome Measures

Primary Outcomes (1)

• Death or neurodevelopmental impairment (MDI <70; PDI <70; cerebral palsy; blindness; or severe hearing loss)

  0-22 months corrected age

Secondary Outcomes (9)

• Patent ductus arteriosus requiring drug or surgical treatment

  36 weeks post conceptual age

• Retinopathy of prematurity

  36 weeks post conceptual age

• Bronchopulmonary dysplasia (BPD)

  36 weeks post conceptual age

• Ventilator settings and FiO2 at 36 weeks

  36 weeks post conceptual age

• Necrotizing enterocolitis (NEC)

  120 days old or at discharge

Study Arms (4)

Aggressive ELBW

ACTIVE COMPARATOR

In Aggressive group 1, infants with birth weights 501-750g.

Procedure: Aggressive Phototherapy 501-750g

Aggressive VLBW

ACTIVE COMPARATOR

In the Aggressive group 2, infants with birth weights 751-1000g.

Procedure: Aggressive Phototherapy 751-1000g

Conservative ELBW

ACTIVE COMPARATOR

In the Conservative group 1, infants with birth weights 501-750g.

Procedure: Conservative Phototherapy 501-750g

Conservative VLBW

ACTIVE COMPARATOR

In the Conservative group 2, infants with birth weights 751-1000g.

Procedure: Conservative Phototherapy 751-1000g

Interventions

Aggressive Phototherapy 501-750g PROCEDURE

Phototherapy started, stopped, and/or restarted when total serum bilirubin levels reach 5 mg/dl during days of life 1-14.

Aggressive ELBW

Aggressive Phototherapy 751-1000g PROCEDURE

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.

Aggressive VLBW

Conservative Phototherapy 501-750g PROCEDURE

Phototherapy started, stopped, and/or restarted when total serum bilirubin levels reach ≥8.0 mg/dl during days of life 1-14.

Conservative ELBW

Conservative Phototherapy 751-1000g PROCEDURE

Phototherapy started, stopped, and/or restarted when total serum bilirubin levels reach ≥10.0 mg/dl during days of life 1-14.

Conservative VLBW

Eligibility Criteria

• Age: 12 Hours - 36 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• grams birth weight
• hours postnatal age

You may not qualify if:

• 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

Sponsors & Collaborators

• NICHD Neonatal Research Network: lead
• National Center for Research Resources (NCRR): collaborator

Study Sites (17)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

University of California at San Diego

San Diego, California, 92103-8774, United States

Location

Yale University

New Haven, Connecticut, 06504, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Emory University

Atlanta, Georgia, 30303, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Wake Forest University

Charlotte, North Carolina, 27157, United States

Location

RTI International

Durham, North Carolina, 27705, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Medical Center

Cincinnati, Ohio, 45267, United States

Location

Case Western Reserve University, Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Brown University, Women & Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75235, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Related Publications (4)

• Morris BH, Oh W, Tyson JE, Stevenson DK, Phelps DL, O'Shea TM, McDavid GE, Perritt RL, Van Meurs KP, Vohr BR, Grisby C, Yao Q, Pedroza C, Das A, Poole WK, Carlo WA, Duara S, Laptook AR, Salhab WA, Shankaran S, Poindexter BB, Fanaroff AA, Walsh MC, Rasmussen MR, Stoll BJ, Cotten CM, Donovan EF, Ehrenkranz RA, Guillet R, Higgins RD; NICHD Neonatal Research Network. Aggressive vs. conservative phototherapy for infants with extremely low birth weight. N Engl J Med. 2008 Oct 30;359(18):1885-96. doi: 10.1056/NEJMoa0803024.

  PMID: 18971491 RESULT

• Ahlfors CE, Vreman HJ, Wong RJ, Bender GJ, Oh W, Morris BH, Stevenson DK; Phototherapy Subcommittee; National Institute of Child Health and Development (NICHD) Neonatal Research Network. Effects of sample dilution, peroxidase concentration, and chloride ion on the measurement of unbound bilirubin in premature newborns. Clin Biochem. 2007 Feb;40(3-4):261-7. doi: 10.1016/j.clinbiochem.2006.09.006. Epub 2006 Sep 29.

  PMID: 17069786 RESULT

• Bender GJ, Cashore WJ, Oh W. Ontogeny of bilirubin-binding capacity and the effect of clinical status in premature infants born at less than 1300 grams. Pediatrics. 2007 Nov;120(5):1067-73. doi: 10.1542/peds.2006-3024.

  PMID: 17974745 RESULT

• Oh W, Stevenson DK, Tyson JE, Morris BH, Ahlfors CE, Bender GJ, Wong RJ, Perritt R, Vohr BR, Van Meurs KP, Vreman HJ, Das A, Phelps DL, O'Shea TM, Higgins RD; NICHD Neonatal Research Network Bethesda MD. Influence of clinical status on the association between plasma total and unbound bilirubin and death or adverse neurodevelopmental outcomes in extremely low birth weight infants. Acta Paediatr. 2010 May;99(5):673-678. doi: 10.1111/j.1651-2227.2010.01688.x. Epub 2010 Jan 25.

  PMID: 20105142 RESULT

Related Links

• NICHD Neonatal Research Network

MeSH Terms

Conditions

Hyperbilirubinemia, Neonatal; Jaundice, Neonatal; Premature Birth

Condition Hierarchy (Ancestors)

Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperbilirubinemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• 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

  Children's Hospital Medical Center, Cincinnati

  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 University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK

Study Record Dates

• First Submitted: June 15, 2005
• First Posted: June 16, 2005
• Study Start: September 1, 2002
• Primary Completion: April 1, 2005
• Study Completion: November 1, 2007
• Last Updated: March 22, 2019

Record last verified: 2017-09

Locations

US (17)