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

Hyperbilirubinemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01944696
• Other study ID #: HSC-MS-13-0406
• Status: Recruiting
• Phase: N/A
• First received: September 12, 2013
• Last updated: June 15, 2016
• Start date: March 2014
• Est. completion date: January 2018

Study information

• Verified date: June 2016
• Source: The University of Texas Health Science Center, Houston
• Contact: Jon E Tyson, MD
• Phone: 713-500-5651
• Email: jon.e.tyson[@]uth.tmc.edu
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 210
• Est. completion date: January 2018
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 24 Hours

Eligibility

Inclusion Criteria:

• birth weight 401-1000 grams

• age less than or equal to 24 hours

Exclusion Criteria:

• hemolytic disease

• major anomaly

• overt nonbacterial infection

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Birth Weight
• Extremely Low Birth Weight
• Hyperbilirubinemia
• Premature Birth
• Premature Newborns

Intervention

Other:
• 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 .

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham School of Medicine - UAB Hospital	Birmingham	Alabama
United States	University of Cincinnati College of Medicine - Good Samaritan Hospital	Cincinnati	Ohio
United States	The University of Texas Southwestern Medical School - Clements University Hospital	Dallas	Texas
United States	The University of Texas Health Science Center at Houston; Memorial Hermann-TMC-NICU	Houston	Texas
United States	Stanford University - Lucile Packard Children's Hospital	Palo Alto	California
United States	The University of Texas Health Science Center at San Antonio - University Hospital	San Antonio	Texas

Sponsors (3)

Lead Sponsor	Collaborator
The University of Texas Health Science Center, Houston	Lucile Packard Children's Hospital, Stanford University

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Neurodevelopmental status	The Network supports and assures carefully standardized neurodevelopmental testing at 2 years adjusted age for inborn ELBW patients. The reliability of these exams is verified annually in the Network. These assessments will provide data for survival rates without impairment	2 years adjusted age	Yes
Other	Survival	The Neonatal Research Network supports and assures outcome assessment at 2 years adjusted age for inborn ELBW patients. These assessments will provide data for survival rates and survival rates without impairment	Before discharge from the neonatal ICU and at 2 years adjusted age	Yes
Primary	Brain stem auditory evoked response wave V latency	a measure of transient or permanent bilirubin neurotoxicity	35 wks postmenstrual age or discharge	Yes
Secondary	Peak Total Serum Bilirubin (tsb)	Total serum bilirubin (TSB) measurements will be obtained following a study protocol modeled on standard practice for monitoring TSB in ELBW newborns.	14 days from birth	Yes