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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Hyperbilirubinemia, Premature Newborns, Extremely Low Birth Weight

Intervention / Treatment
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* Other: phototherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: birth weight 401-1000 grams age less than or equal to 24 hours Exclusion Criteria: hemolytic disease major anomaly overt nonbacterial infection

Ages Eligible for Study
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Maximum Age: 24 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: continuous (uninterrupted) phototherapy<br>standard phototherapy | Other: phototherapy<br>* Cycled versus continuous phototherapy during the first 2 wks after birth, both administered at bilirubin thresholds used in the NICHD Neonatal Network Phototherapy trial .<br>|
| Experimental: 15 minute per hour cycled phototherapy<br>15 minute per hour cycled phototherapy | Other: phototherapy<br>* Cycled versus continuous phototherapy during the first 2 wks after birth, both administered at bilirubin thresholds used in the NICHD Neonatal Network Phototherapy trial .<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain stem auditory evoked response wave V latency | a measure of transient or permanent bilirubin neurotoxicity | 35 wks postmenstrual age or discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hyperbilirubinemia, prematurity, extremely low birth weight (ELBW), phototherapy, cycled phototherapy, intermittent phototherapy