Cycled Phototherapy: A Safer Effective Treatment for Small Premature Infants?

NCT ID: NCT01944696

Last Updated: 2016-06-16

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 210 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2018-01-31

Brief Summary

Cycled (intermittent) phototherapy will be compared to continuous (uninterrupted) phototherapy in the treatment of hyperbilirubinemia (newborn jaundice) in extremely low birth weight newborns in a pilot randomized controlled trial.

Hypothesis: Cycled phototherapy (PT) will provide the same benefits as continuous phototherapy in extremely low birth weight (ELBW) infants without the risks that have been associated with continuous phototherapy.

Detailed Description

Phototherapy (PT) is widely used and assumed to be safe as well as effective in reducing total bilirubin (TB) levels. Our recent NICHD Network Trial showed that aggressive use of phototherapy reduces neurodevelopmental impairment (NDI), but may increase deaths among ELBW infants. Among ventilator treated infants <750 g birth weight (BW) (n =696), conservative Bayesian analyses (using a neutral prior probability) identified a 99% (posterior) probability that aggressive phototherapy reduced profound NDI but a 99% probability that it increased deaths relative to conservative phototherapy. The possibility that PT increases deaths among high risk infants is also suggested by the Collaborative Phototherapy trial (performed in the 1970s), the only large RCT in which LBW infants were randomly assigned to receive PT or no PT. The relative risk for death among those randomized to PT relative to those randomized to no PT was 1.32 (0.9-1.82) among all LBW infants and 1.49 (0.93-2.40) among ELBW infants. These findings are consistent with a major increase in mortality but have been ignored because the p was >0.05, an error often made in ignoring important potential treatment hazards when power is limited.

Multiple studies, most performed decades ago in larger infants, found that short on/off cycles of PT (e.g. 15 min on/60 min off, 1 h on/3 h off, or 1 h on/1 h off ) are as effective as uninterrupted PT to reduce TSB. (Cycles with >6 h off PT do not appear to be as effective as uninterrupted PT). The clinical use of uninterrupted rather than cycled PT appears to be based largely on the assumption that PT is safe for all infants.

Conditions

Hyperbilirubinemia; Premature Newborns; Extremely Low Birth Weight

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

continuous (uninterrupted) phototherapy

standard phototherapy

Group Type: ACTIVE_COMPARATOR

phototherapy

Intervention Type: OTHER

Cycled versus continuous phototherapy during the first 2 wks after birth, both administered at bilirubin thresholds used in the NICHD Neonatal Network Phototherapy trial .

15 minute per hour cycled phototherapy

15 minute per hour cycled phototherapy

Group Type: EXPERIMENTAL

phototherapy

Intervention Type: OTHER

Cycled versus continuous phototherapy during the first 2 wks after birth, both administered at bilirubin thresholds used in the NICHD Neonatal Network Phototherapy trial .

Interventions

phototherapy

Cycled versus continuous phototherapy during the first 2 wks after birth, both administered at bilirubin thresholds used in the NICHD Neonatal Network Phototherapy trial .

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• birth weight 401-1000 grams
• age less than or equal to 24 hours

Exclusion Criteria

• hemolytic disease
• major anomaly
• overt nonbacterial infection

• Maximum Eligible Age: 24 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stanford University

OTHER

Sponsor Role: collaborator

Lucile Packard Children's Hospital

OTHER

Sponsor Role: collaborator

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: lead

Responsible Party

Jon Edward Tyson

Professor, Vice Dean for Clinical Research and Healthcare Quality

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jon E Tyson, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center, Houston

David K Stevenson, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford School of Medicine

Locations

University of Alabama at Birmingham School of Medicine - UAB Hospital

Birmingham, Alabama, United States

Site Status: RECRUITING

Stanford University - Lucile Packard Children's Hospital

Palo Alto, California, United States

Site Status: NOT_YET_RECRUITING

University of Cincinnati College of Medicine - Good Samaritan Hospital

Cincinnati, Ohio, United States

Site Status: RECRUITING

The University of Texas Southwestern Medical School - Clements University Hospital

Dallas, Texas, United States

Site Status: RECRUITING

The University of Texas Health Science Center at Houston; Memorial Hermann-TMC-NICU

Houston, Texas, United States

Site Status: RECRUITING

The University of Texas Health Science Center at San Antonio - University Hospital

San Antonio, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jon E Tyson, MD

Role: CONTACT

jon.e.tyson@uth.tmc.edu

713-500-5651

Cody C Arnold, MD

Role: CONTACT

cody.c.arnold@uth.tmc.edu

(713) 500-5633

Facility Contacts

Wally F Carlo, MD

Role: primary

WCarlo@peds.uab.edu

David K Stevenson, MD

Role: primary

dstevenson@stanford.edu

Ron Wong, MD

Role: backup

rjwong@stanford.edu

Brenda Poindexter, MD, MS

Role: primary

Brenda.Poindexter@cchmc.org

Myra Wyckoff, MD

Role: primary

Myra.Wyckoff@UTSouthwestern.edu

Jon E Tyson, MD

Role: primary

jon.e.tyson@uth.tmc.edu

713-500-5651

Cody C Arnold, MD

Role: backup

cody.c.arnold@uth.tmc.edu

(713) 500-5633

Alvaro Moreira, MD

Role: primary

moreiraA@uthscsa.edu

References

Tyson JE, Pedroza C, Langer J, Green C, Morris B, Stevenson D, Van Meurs KP, Oh W, Phelps D, O'Shea M, McDavid GE, Grisby C, Higgins R; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Does aggressive phototherapy increase mortality while decreasing profound impairment among the smallest and sickest newborns? J Perinatol. 2012 Sep;32(9):677-84. doi: 10.1038/jp.2012.64. Epub 2012 May 31.

Reference Type: BACKGROUND

PMID: 22652561 (View on PubMed)

Hintz SR, Stevenson DK, Yao Q, Wong RJ, Das A, Van Meurs KP, Morris BH, Tyson JE, Oh W, Poole WK, Phelps DL, McDavid GE, Grisby C, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Is phototherapy exposure associated with better or worse outcomes in 501- to 1000-g-birth-weight infants? Acta Paediatr. 2011 Jul;100(7):960-5. doi: 10.1111/j.1651-2227.2011.02175.x. Epub 2011 Feb 25.

Reference Type: BACKGROUND

PMID: 21272067 (View on PubMed)

Arnold C, Tyson JE, Pedroza C, Carlo WA, Stevenson DK, Wong R, Dempsey A, Khan A, Fonseca R, Wyckoff M, Moreira A, Lasky R. Cycled Phototherapy Dose-Finding Study for Extremely Low-Birth-Weight Infants: A Randomized Clinical Trial. JAMA Pediatr. 2020 Jul 1;174(7):649-656. doi: 10.1001/jamapediatrics.2020.0559.

Reference Type: DERIVED

PMID: 32338720 (View on PubMed)

Other Identifiers

HSC-MS-13-0406

Identifier Type: -

Identifier Source: org_study_id