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

NCT ID: NCT00114543

Last Updated: 2019-03-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1974 participants

Study Classification

INTERVENTIONAL

Study Start Date

2002-09-30

Study Completion Date

2007-11-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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Aggressive ELBW

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

Group Type ACTIVE_COMPARATOR

Aggressive Phototherapy 501-750g

Intervention Type PROCEDURE

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

Aggressive VLBW

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

Group Type ACTIVE_COMPARATOR

Aggressive Phototherapy 751-1000g

Intervention Type 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.

Conservative ELBW

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

Group Type ACTIVE_COMPARATOR

Conservative Phototherapy 501-750g

Intervention Type PROCEDURE

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

Conservative VLBW

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

Group Type ACTIVE_COMPARATOR

Conservative Phototherapy 751-1000g

Intervention Type PROCEDURE

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

Interventions

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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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type PROCEDURE

Eligibility Criteria

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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
Minimum Eligible Age

12 Hours

Maximum Eligible Age

36 Hours

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Center for Research Resources (NCRR)

NIH

Sponsor Role collaborator

NICHD Neonatal Research Network

NETWORK

Sponsor Role lead

Responsible Party

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University of Texas Health Science Center at Houston

Principal Investigators

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Abbot R. Laptook, MD

Role: PRINCIPAL_INVESTIGATOR

Brown University, Women & Infants Hospital of Rhode Island

Michele C. Walsh, MD MS

Role: PRINCIPAL_INVESTIGATOR

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

Ronald N. Goldberg, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Brenda B. Poindexter, MD MS

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Abhik Das, PhD

Role: PRINCIPAL_INVESTIGATOR

RTI International

Ronnie Guillet, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University of Rochester

Pablo J. Sanchez, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas, Southwestern Medical Center at Dallas

Barbara J. Stoll, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Krisa P. Van Meurs, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Neil N. Finer, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Kurt Schibler, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Medical Center, Cincinnati

Waldemar A. Carlo, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Brenda H. Morris, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center, Houston

Seetha Shankaran, MD

Role: PRINCIPAL_INVESTIGATOR

Wayne State University

Richard A. Ehrenkranz, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Shahnaz Duara, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

T. Michael O'Shea, MD MPH

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Stanford University

Palo Alto, California, United States

Site Status

University of California at San Diego

San Diego, California, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Indiana University

Indianapolis, Indiana, United States

Site Status

Wayne State University

Detroit, Michigan, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

Wake Forest University

Charlotte, North Carolina, United States

Site Status

RTI International

Durham, North Carolina, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

Cincinnati Children's Medical Center

Cincinnati, Ohio, United States

Site Status

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

Cleveland, Ohio, United States

Site Status

Brown University, Women & Infants Hospital of Rhode Island

Providence, Rhode Island, United States

Site Status

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, United States

Site Status

University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status

Countries

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United States

References

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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.

Reference Type RESULT
PMID: 18971491 (View on PubMed)

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.

Reference Type RESULT
PMID: 17069786 (View on PubMed)

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.

Reference Type RESULT
PMID: 17974745 (View on PubMed)

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.

Reference Type RESULT
PMID: 20105142 (View on PubMed)

Related Links

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https://neonatal.rti.org/

NICHD Neonatal Research Network

Other Identifiers

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M01RR016587

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR000030

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR000032

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR000039

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR000044

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR006022

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR000633

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR000070

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR007122

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR000750

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR000080

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR008084

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01HD036790

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD021364

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD021373

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD021385

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD021397

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027851

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027853

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027856

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027871

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027880

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027904

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD034216

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD040461

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD040492

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD040498

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD040521

Identifier Type: NIH

Identifier Source: secondary_id

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U10HD040689

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NICHD-NRN-0029

Identifier Type: -

Identifier Source: org_study_id

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