Cycled Phototherapy: A Safer Effective Treatment for Small Premature Infants?
Primary Purpose
Hyperbilirubinemia, Premature Newborns, Extremely Low Birth Weight
Status
Unknown status
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
phototherapy
Sponsored by
About this trial
This is an interventional prevention trial for Hyperbilirubinemia focused on measuring hyperbilirubinemia, prematurity, extremely low birth weight (ELBW), phototherapy, cycled phototherapy, intermittent phototherapy
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
Sites / Locations
- University of Alabama at Birmingham School of Medicine - UAB HospitalRecruiting
- Stanford University - Lucile Packard Children's Hospital
- University of Cincinnati College of Medicine - Good Samaritan HospitalRecruiting
- The University of Texas Southwestern Medical School - Clements University HospitalRecruiting
- The University of Texas Health Science Center at Houston; Memorial Hermann-TMC-NICURecruiting
- The University of Texas Health Science Center at San Antonio - University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
continuous (uninterrupted) phototherapy
15 minute per hour cycled phototherapy
Arm Description
standard phototherapy
15 minute per hour cycled phototherapy
Outcomes
Primary Outcome Measures
Brain stem auditory evoked response wave V latency
a measure of transient or permanent bilirubin neurotoxicity
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT01944696
First Posted
September 12, 2013
Last Updated
June 15, 2016
Sponsor
The University of Texas Health Science Center, Houston
Collaborators
Stanford University, Lucile Packard Children's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT01944696
Brief Title
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
2. Study Status
Record Verification Date
June 2016
Overall Recruitment Status
Unknown status
Study Start Date
March 2014 (undefined)
Primary Completion Date
January 2017 (Anticipated)
Study Completion Date
January 2018 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The University of Texas Health Science Center, Houston
Collaborators
Stanford University, Lucile Packard Children's Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperbilirubinemia, Premature Newborns, Extremely Low Birth Weight
Keywords
hyperbilirubinemia, prematurity, extremely low birth weight (ELBW), phototherapy, cycled phototherapy, intermittent phototherapy
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
210 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
continuous (uninterrupted) phototherapy
Arm Type
Active Comparator
Arm Description
standard phototherapy
Arm Title
15 minute per hour cycled phototherapy
Arm Type
Experimental
Arm Description
15 minute per hour cycled phototherapy
Intervention Type
Other
Intervention Name(s)
phototherapy
Intervention Description
Cycled versus continuous phototherapy during the first 2 wks after birth, both administered at bilirubin thresholds used in the NICHD Neonatal Network Phototherapy trial .
Primary Outcome Measure Information:
Title
Brain stem auditory evoked response wave V latency
Description
a measure of transient or permanent bilirubin neurotoxicity
Time Frame
35 wks postmenstrual age or discharge
Secondary Outcome Measure Information:
Title
Peak Total Serum Bilirubin (tsb)
Description
Total serum bilirubin (TSB) measurements will be obtained following a study protocol modeled on standard practice for monitoring TSB in ELBW newborns.
Time Frame
14 days from birth
Other Pre-specified Outcome Measures:
Title
Neurodevelopmental status
Description
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
Time Frame
2 years adjusted age
Title
Survival
Description
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
Time Frame
Before discharge from the neonatal ICU and at 2 years adjusted age
10. Eligibility
Sex
All
Maximum Age & Unit of Time
24 Hours
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jon E Tyson, MD
Phone
713-500-5651
Email
jon.e.tyson@uth.tmc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Cody C Arnold, MD
Phone
(713) 500-5633
Email
cody.c.arnold@uth.tmc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jon E Tyson, MD
Organizational Affiliation
The University of Texas Health Science Center, Houston
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David K Stevenson, MD
Organizational Affiliation
Stanford School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham School of Medicine - UAB Hospital
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wally F Carlo, MD
Email
WCarlo@peds.uab.edu
First Name & Middle Initial & Last Name & Degree
Wally F Carlo, MD
Facility Name
Stanford University - Lucile Packard Children's Hospital
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David K Stevenson, MD
Email
dstevenson@stanford.edu
First Name & Middle Initial & Last Name & Degree
Ron Wong, MD
Email
rjwong@stanford.edu
First Name & Middle Initial & Last Name & Degree
David K Stevenson, MD
First Name & Middle Initial & Last Name & Degree
Ron Wong, MD
Facility Name
University of Cincinnati College of Medicine - Good Samaritan Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45220
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brenda Poindexter, MD, MS
Email
Brenda.Poindexter@cchmc.org
First Name & Middle Initial & Last Name & Degree
Brenda Poindexter, MD, MS
Facility Name
The University of Texas Southwestern Medical School - Clements University Hospital
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Myra Wyckoff, MD
Email
Myra.Wyckoff@UTSouthwestern.edu
First Name & Middle Initial & Last Name & Degree
Myra Wyckoff, MD
Facility Name
The University of Texas Health Science Center at Houston; Memorial Hermann-TMC-NICU
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jon E Tyson, MD
Phone
713-500-5651
Email
jon.e.tyson@uth.tmc.edu
First Name & Middle Initial & Last Name & Degree
Cody C Arnold, MD
Phone
(713) 500-5633
Email
cody.c.arnold@uth.tmc.edu
First Name & Middle Initial & Last Name & Degree
Joh E Tyson, MD
First Name & Middle Initial & Last Name & Degree
Cody C Arnold, MD
First Name & Middle Initial & Last Name & Degree
Mona Khan, MD
Facility Name
The University of Texas Health Science Center at San Antonio - University Hospital
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alvaro Moreira, MD
Email
moreiraA@uthscsa.edu
First Name & Middle Initial & Last Name & Degree
Alvaro Moreira, MD
12. IPD Sharing Statement
Citations:
PubMed Identifier
22652561
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.
Results Reference
background
PubMed Identifier
21272067
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.
Results Reference
background
PubMed Identifier
32338720
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. Erratum In: JAMA Pediatr. 2020 Jul 1;174(7):732.
Results Reference
derived
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Cycled Phototherapy: A Safer Effective Treatment for Small Premature Infants?
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