Clinical trial NCT01944696: Cycled Phototherapy: A Safer Effective Treatment for Small Premature Infants?
Official title: Cycled Phototherapy: A Safer Effective Treatment for Small Premature Infants?
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hyperbilirubinemia
Premature Newborns
Extremely Low Birth Weight
Keywords: hyperbilirubinemia
prematurity
extremely low birth weight (ELBW)
phototherapy
cycled phototherapy
intermittent phototherapy
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
Collaborators: name: Stanford University
name: Lucile Packard Children's Hospital
First posted: 2013-09-18
Enrollment: 210
Sex: ALL
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Brain stem auditory evoked response wave V latency
timeFrame: 35 wks postmenstrual age or discharge
Secondary outcomes:
measure: Peak Total Serum Bilirubin (tsb)
timeFrame: 14 days from birth
Other outcomes:
measure: Neurodevelopmental status
timeFrame: 2 years adjusted age
measure: Survival
timeFrame: Before discharge from the neonatal ICU and at 2 years adjusted age
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham School of Medicine - UAB Hospital
state: Alabama
city: Palo Alto
country: United States
facility: Stanford University - Lucile Packard Children's Hospital
state: California
city: Cincinnati
country: United States
facility: University of Cincinnati College of Medicine - Good Samaritan Hospital
state: Ohio
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical School - Clements University Hospital
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston; Memorial Hermann-TMC-NICU
state: Texas
city: San Antonio
country: United States
facility: The University of Texas Health Science Center at San Antonio - University Hospital
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Jon E Tyson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford School of Medicine
name: David K Stevenson, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
citation: 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.