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Hyperbilirubinemia, NeonatalPhase 3PhototherapyNCT00114543

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

A Phase 3 study testing Aggressive Phototherapy 501-750g, Aggressive Phototherapy 751-1000g and Conservative Phototherapy 501-750g in people with Hyperbilirubinemia, Neonatal and Jaundice, Neonatal, run by NICHD Neonatal Research Network at 17 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 12 to 36 hours
What is being tested?
Aggressive Phototherapy 501-750g, Aggressive Phototherapy 751-1000g and Conservative Phototherapy 501-750g
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,974 participants
Where
17 sitesUnited States
Study dates
Sep 2002to Nov 2007
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 36 hours
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

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

Who cannot join

  • 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

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

United States17 sites
  • Emory University

    Atlanta, Georgia, 30303

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35233

  • Wake Forest University

    Charlotte, North Carolina, 27157

  • Cincinnati Children's Medical Center

    Cincinnati, Ohio, 45267

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

    Cleveland, Ohio, 44106

  • University of Texas Southwestern Medical Center at Dallas

    Dallas, Texas, 75235

  • Wayne State University

    Detroit, Michigan, 48201

  • RTI International

    Durham, North Carolina, 27705

  • Duke University

    Durham, North Carolina, 27710

  • University of Texas Health Science Center at Houston

    Houston, Texas, 77030

  • Indiana University

    Indianapolis, Indiana, 46202

  • University of Miami

    Miami, Florida, 33136

  • Yale University

    New Haven, Connecticut, 06504

  • Stanford University

    Palo Alto, California, 94304

  • Brown University, Women & Infants Hospital of Rhode Island

    Providence, Rhode Island, 02905

  • University of Rochester

    Rochester, New York, 14642

  • University of California at San Diego

    San Diego, California, 92103-8774

Other trials in United States

About this study

Official title: A Randomized Trial of Aggressive or Conservative Phototherapy for Extremely Low Birth Weight Infants

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.

Read the 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.

Being tested
Aggressive Phototherapy 501-750g, Aggressive Phototherapy 751-1000g, Conservative Phototherapy 501-750g, Conservative Phototherapy 751-1000g
Keywords
NICHD Neonatal Research Network, Bilirubin, Phototherapy, Very Low Birth Weight (VLBW), Extremely Low Birth Weight (ELBW), Prematurity, Neurodevelopmental outcome
Medical subject headings
Hyperbilirubinemia, Neonatal, Jaundice, Neonatal, Premature Birth

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Aggressive Phototherapy 501-750gProcedure or surgery

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

  • Aggressive Phototherapy 751-1000gProcedure or surgery

    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 Phototherapy 501-750gProcedure or surgery

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

  • Conservative Phototherapy 751-1000gProcedure or surgery

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

Study groups in NCT00114543
Study groupRoleWhat they receive
Aggressive ELBWActive comparatorIn Aggressive group 1, infants with birth weights 501-750g.
Receives: Procedure: Aggressive Phototherapy 501-750g
Aggressive VLBWActive comparatorIn the Aggressive group 2, infants with birth weights 751-1000g.
Receives: Procedure: Aggressive Phototherapy 751-1000g
Conservative ELBWActive comparatorIn the Conservative group 1, infants with birth weights 501-750g.
Receives: Procedure: Conservative Phototherapy 501-750g
Conservative VLBWActive comparatorIn the Conservative group 2, infants with birth weights 751-1000g.
Receives: Procedure: Conservative Phototherapy 751-1000g

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 0-22 months corrected age

Secondary outcomes (9)
  1. Patent ductus arteriosus requiring drug or surgical treatment

    Measured: 36 weeks post conceptual age

  2. Retinopathy of prematurity

    Measured: 36 weeks post conceptual age

  3. Bronchopulmonary dysplasia (BPD)

    Measured: 36 weeks post conceptual age

  4. Ventilator settings and FiO2 at 36 weeks

    Measured: 36 weeks post conceptual age

  5. Necrotizing enterocolitis (NEC)

    Measured: 120 days old or at discharge

  6. Intraventricular hemorrhage (IVH) by grade

    Measured: 120 days old or at discharge

  7. Periventricular leukomalacia

    Measured: 120 days old or at discharge

  8. Sepsis

    Measured: 120 days old or at discharge

  9. Hearing assessments

    Measured: 120 days old or at discharge

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jun 2005 (estimated)
  2. Study startSep 2002
  3. Primary completionApr 2005
  4. Study completionNov 2007

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
1,974 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00114543
Sponsor's protocol ID
NICHD-NRN-0029
Other IDs
M01RR016587, M01RR000030, M01RR000032, M01RR000039, M01RR000044, M01RR006022, M01RR000633, M01RR000070
Acronym
Phototherapy
Status last verified
Sep 2017
First submitted
15 Jun 2005
Last updated
22 Mar 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 18971491
  • 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.

    PubMed 17069786
  • 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.

    PubMed 17974745
  • 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.

    PubMed 20105142

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Aggressive Phototherapy 501-750g, Aggressive Phototherapy 751-1000g and Conservative Phototherapy 501-750g in people with Hyperbilirubinemia, Neonatal and Jaundice, Neonatal, run by NICHD Neonatal Research Network at 17 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Death or neurodevelopmental impairment (MDI <70; PDI <70; cerebral palsy; blindness; or severe hearing loss) (time frame: 0-22 months corrected age). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00114543, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2019.

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