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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00114543
Other study ID # NICHD-NRN-0029
Secondary ID M01RR016587M01RR
Status Completed
Phase Phase 3
First received
Last updated
Start date September 2002
Est. completion date November 2007

Study information

Verified date September 2017
Source NICHD Neonatal Research Network
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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 either aggressive or conservative threshold limits. 1,978 infants were enrolled.


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.


Recruitment information / eligibility

Status Completed
Enrollment 1974
Est. completion date November 2007
Est. primary completion date April 2005
Accepts healthy volunteers No
Gender All
Age group N/A to 36 Hours
Eligibility 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

Study Design


Intervention

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.
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.
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.
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.

Locations

Country Name City State
United States Emory University Atlanta Georgia
United States University of Alabama at Birmingham Birmingham Alabama
United States Wake Forest University Charlotte North Carolina
United States Cincinnati Children's Medical Center Cincinnati Ohio
United States Case Western Reserve University, Rainbow Babies and Children's Hospital Cleveland Ohio
United States University of Texas Southwestern Medical Center at Dallas Dallas Texas
United States Wayne State University Detroit Michigan
United States Duke University Durham North Carolina
United States RTI International Durham North Carolina
United States University of Texas Health Science Center at Houston Houston Texas
United States Indiana University Indianapolis Indiana
United States University of Miami Miami Florida
United States Yale University New Haven Connecticut
United States Stanford University Palo Alto California
United States Brown University, Women & Infants Hospital of Rhode Island Providence Rhode Island
United States University of Rochester Rochester New York
United States University of California at San Diego San Diego California

Sponsors (2)

Lead Sponsor Collaborator
NICHD Neonatal Research Network National Center for Research Resources (NCRR)

Country where clinical trial is conducted

United States, 

References & Publications (4)

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 i — View Citation

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. — View Citation

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, Rasmuss — View Citation

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 bet — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Death or neurodevelopmental impairment (MDI <70; PDI <70; cerebral palsy; blindness; or severe hearing loss) 0-22 months corrected age
Secondary Patent ductus arteriosus requiring drug or surgical treatment 36 weeks post conceptual age
Secondary Retinopathy of prematurity 36 weeks post conceptual age
Secondary Bronchopulmonary dysplasia (BPD) 36 weeks post conceptual age
Secondary Ventilator settings and FiO2 at 36 weeks 36 weeks post conceptual age
Secondary Necrotizing enterocolitis (NEC) 120 days old or at discharge
Secondary Intraventricular hemorrhage (IVH) by grade 120 days old or at discharge
Secondary Periventricular leukomalacia 120 days old or at discharge
Secondary Sepsis 120 days old or at discharge
Secondary Hearing assessments 120 days old or at discharge
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