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

Infant, Premature Clinical Trial

— Phototherapy  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00114543
• Other study ID #: NICHD-NRN-0029
• Secondary ID: M01RR016587M01RR
• Status: Completed
• Phase: Phase 3
• 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
• 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

Related Conditions & MeSH terms

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

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

External Links

•   NICHD Neonatal Research Network