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Cycled Phototherapy

Primary Purpose

Hyper Bilirubinemia, Premature Infant

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Phototherapy lights
Sponsored by
NICHD Neonatal Research Network
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hyper Bilirubinemia focused on measuring Infant, Newborn, Diseases, Phototherapy

Eligibility Criteria

22 Weeks - 27 Weeks (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Infants is inborn
  2. Infant is ≤ 750 grams at birth and/or < 27 weeks gestation at birth by best OB estimate
  3. Infant is 12-36 hours of age.

Exclusion Criteria:

  1. Unable to enroll infant by 36 hours of age
  2. Previous phototherapy
  3. Known hemolytic disease
  4. TSB reported as >6.0 mg/dL before 12 hours age
  5. Major anomaly
  6. Overt nonbacterial infection
  7. Infant is likely to expire soon: Limiting or withdrawal of intensive care is being recommended to the parents, the parents are requesting withdrawal of care, or the pH is < 6.80 or persistent bradycardia with hypoxemia for >2h.

Sites / Locations

  • University of Alabama at BirminghamRecruiting
  • Stanford UniversityRecruiting
  • Emory UniversityRecruiting
  • University of IowaRecruiting
  • University of New MexicoRecruiting
  • University of RochesterRecruiting
  • RTI International
  • Duke UniversityRecruiting
  • Cincinnati Children's Medical CenterRecruiting
  • Case Western Reserve University, Rainbow Babies and Children's HospitalRecruiting
  • Research Institute at Nationwide Children's HospitalRecruiting
  • Univeristy of PennsylvaniaRecruiting
  • Brown University - Women and Infants Hospital of Rhode IslandRecruiting
  • University of Texas Southwestern Medical Center at DallasRecruiting
  • University of Texas Health Science Center at HoustonRecruiting
  • University of UtahRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Continuous Phototherapy

Cycled Phototherapy

Arm Description

Continuous phototherapy

Cycled phototherapy at timed intervals, dependent upon total serum bilirum (TSB) levels.

Outcomes

Primary Outcome Measures

Number of participants survival to discharge
Number of Participants discharged from hospital alive, after birth.

Secondary Outcome Measures

Number of hours of Phototherapy
The reported values will be the mean total hours of phototherapy during the two week intervention period.
Number of irradiance hours
The reported values will be the mean total hours of irradiance during the two week intervention period.
Peak Concentration of Total Serum Bilirubin
The reported values will be the mean peak total serum bilirubin (mg/dL) during the two week intervention period.
Concentration of Total Serum Bilirubin
The reported values will be the mean total serum bilirubin (mg/dL) during the two week intervention period.
Number of Participants with Major neonatal morbidity
Major neonatal morbidity is defined as a severe ICH, ventricular enlargement of cystic white matter disease, BPD, late onset sepsis, NEC or spontaneous intestinal perforation, or >grade 3 ROP before discharge.
Number of Participants with Severe ICH, as a component of the predischarge morbidity
As recorded for the sonongram with the most severe finding in the blood/echodensity in the ventricle or blood/echodensity in the parenchyma
Number of Participants with Ventricular enlargement of cystic white matter disease, as a component predischarge morbidity
If a MRI was done: ventricular size enlarged, cystic PVL or porencephalic /posthemorrhagic cyst/multicystic encephalomalacia observed. If a MRI was not done: the same items as above for sonograms after day 28.
Number of Participants with Bronchopulmonary dysplasia (BPD), as a component predischarge morbidity
BPD defined as highest FiO2 at 36 wk: >0.21
Number of Participants with Late onset sepsis, as a component predischarge morbidity
Late onset blood culture positive septicemia/bacteremia at >72 hours of age.
Number of Participants with Necrotising enterocolitis (NEC) or spontaneous intestinal perforation, as a component predischarge morbidity
Either proven NEC or spontaneous gastrointestinal perforation without proven NEC.
Number of Participants with Grade 3 (or greater) retinopathy of prematurity (ROP), as a component predischarge morbidity
Stage 3 ROP observed in either eye.
Number of Participants with Patent ductus arteriosus (PDA) treated with surgery or NSAIDS
PDA treated with surgery or NSAIDS (indomethacin, ibuprofen or acetaminophen)
Number of Participants with Neurodevelopmental Impairment
Neurodevelopmental Impairment (NDI), as assessed in a sub-population of follow-up of infants <27 wks gestation. Severe NDI will be defined by any of the following: a BSID III cognitive score < 70, Gross Motor Functional (GMF) Level of 3-5, blindness (<20/200 vision) or profound hearing loss (inability to understand commands despite amplification); moderate NDI will be defined as a BSID III cognitive score 70-84 and either a GMF level of 2 or a hearing deficit requiring amplification to understand commands or unilateral blindness; mild NDI will be defined by a cognitive score 70-84, or a cognitive score ≥ 85 and any of the following: presence of a GMF level 1 or hearing loss not requiring amplification. Normal (no NDI) will be defined by a cognitive score ≥ 85 and absence of any neurosensory deficits.
Number of Participants with Neurodevelopmental Impairment or Death
NDI defined in outcome #9

Full Information

First Posted
April 18, 2019
Last Updated
March 23, 2023
Sponsor
NICHD Neonatal Research Network
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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1. Study Identification

Unique Protocol Identification Number
NCT03927833
Brief Title
Cycled Phototherapy
Official Title
Cycled Phototherapy: A Safer Effective Method to Control the Serum Bilirubin Of Extremely Premature Infants?
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 15, 2020 (Actual)
Primary Completion Date
July 2025 (Anticipated)
Study Completion Date
July 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NICHD Neonatal Research Network
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Cycled phototherapy (PT) is likely to increase survival over that with continuous PT among extremely premature infants (< 750 g BW or <27 weeks GA).
Detailed Description
Were they not delivered early, extremely premature infants would normally develop in darkness within the uterus for 3-4 more months longer before birth. Yet, the routine care of these infants has involved the use of uninterrupted (continuous) exposure to bright light during phototherapy (PT), a treatment method that neonatologists have assumed has no serious adverse effects on even the most immature of newborns. Immaturity, thin translucent skin, and a multitude of other problems may make extremely premature infants highly vulnerable to the photo-oxidative injury, lipid peroxidation, DNA damage, reduced cerebral and mesenteric blood flow, or other serious potential hazards of uninterrupted exposure to PT that have now been identified. Such hazards were not recognized when continuous PT was widely incorporated into neonatal care, and the survival rate of extremely premature infants (<27 wks gestation or <750 g birth weight) was much lower than today. PT rapidly photoisomerizes bilirubin in the subcutaneous tissues and vasculature, and six trials of cycled PT have demonstrated that use of cycled PT reduces the total hours of PT and results in minimal or no increase in peak TSB over that with continuous PT in term or moderately preterm infants. Recent findings from a pilot study (NCT01944696) support a PT regimen for this Cycled Phototherapy protocol. Infants born at one of the Neonatal Research Network centers, ≤ 750 grams at birth and/or < 27 weeks gestation at birth by best OB estimate will be considered for this study. Those who qualify will be randomized to either cycled PT or continuous PT. The cycled phototherapy begins with >15 min/h cycled PT regimen and increased to 30 min/h if the TSB is 8.0-9.9 and 60 min/h if the TSB is >10 mg/dL. Those randomized to continuous phototherapy will undergo continuous exposure,as that is commonly used in NRN centers. The PT lamp position will be adjusted to meet the irradiance (µW/cm2/nm) goal of 22 at the umbilicus. The irradiance goal in both groups will be increased from 22 to 33 at a TSB of 10-13 and to 40 at a TSB >13.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyper Bilirubinemia, Premature Infant
Keywords
Infant, Newborn, Diseases, Phototherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Pragmatic randomized clinical trial addressing patient safety.
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
1700 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Continuous Phototherapy
Arm Type
Active Comparator
Arm Description
Continuous phototherapy
Arm Title
Cycled Phototherapy
Arm Type
Experimental
Arm Description
Cycled phototherapy at timed intervals, dependent upon total serum bilirum (TSB) levels.
Intervention Type
Device
Intervention Name(s)
Phototherapy lights
Intervention Description
Phototherapy lights used continuously or timed, following an algorithm based upon TSB levels.
Primary Outcome Measure Information:
Title
Number of participants survival to discharge
Description
Number of Participants discharged from hospital alive, after birth.
Time Frame
Birth to hospital discharge, up to 120 days of life
Secondary Outcome Measure Information:
Title
Number of hours of Phototherapy
Description
The reported values will be the mean total hours of phototherapy during the two week intervention period.
Time Frame
Start until the end of intervention period (duration of 2 weeks)
Title
Number of irradiance hours
Description
The reported values will be the mean total hours of irradiance during the two week intervention period.
Time Frame
Start until the end of intervention period (duration of 2 weeks)
Title
Peak Concentration of Total Serum Bilirubin
Description
The reported values will be the mean peak total serum bilirubin (mg/dL) during the two week intervention period.
Time Frame
Start until the end of intervention period (duration of 2 weeks)
Title
Concentration of Total Serum Bilirubin
Description
The reported values will be the mean total serum bilirubin (mg/dL) during the two week intervention period.
Time Frame
Start until the end of intervention period (duration of 2 weeks)
Title
Number of Participants with Major neonatal morbidity
Description
Major neonatal morbidity is defined as a severe ICH, ventricular enlargement of cystic white matter disease, BPD, late onset sepsis, NEC or spontaneous intestinal perforation, or >grade 3 ROP before discharge.
Time Frame
Birth to hospital discharge, up to 120 days of life
Title
Number of Participants with Severe ICH, as a component of the predischarge morbidity
Description
As recorded for the sonongram with the most severe finding in the blood/echodensity in the ventricle or blood/echodensity in the parenchyma
Time Frame
Birth to hospital discharge, up to 120 days of life
Title
Number of Participants with Ventricular enlargement of cystic white matter disease, as a component predischarge morbidity
Description
If a MRI was done: ventricular size enlarged, cystic PVL or porencephalic /posthemorrhagic cyst/multicystic encephalomalacia observed. If a MRI was not done: the same items as above for sonograms after day 28.
Time Frame
Birth to hospital discharge, up to 120 days of life
Title
Number of Participants with Bronchopulmonary dysplasia (BPD), as a component predischarge morbidity
Description
BPD defined as highest FiO2 at 36 wk: >0.21
Time Frame
Birth to hospital discharge, up to 120 days of life
Title
Number of Participants with Late onset sepsis, as a component predischarge morbidity
Description
Late onset blood culture positive septicemia/bacteremia at >72 hours of age.
Time Frame
Birth to hospital discharge, up to 120 days of life
Title
Number of Participants with Necrotising enterocolitis (NEC) or spontaneous intestinal perforation, as a component predischarge morbidity
Description
Either proven NEC or spontaneous gastrointestinal perforation without proven NEC.
Time Frame
Birth to hospital discharge, up to 120 days of life
Title
Number of Participants with Grade 3 (or greater) retinopathy of prematurity (ROP), as a component predischarge morbidity
Description
Stage 3 ROP observed in either eye.
Time Frame
Birth to hospital discharge, up to 120 days of life
Title
Number of Participants with Patent ductus arteriosus (PDA) treated with surgery or NSAIDS
Description
PDA treated with surgery or NSAIDS (indomethacin, ibuprofen or acetaminophen)
Time Frame
Birth to hospital discharge, up to 120 days of life
Title
Number of Participants with Neurodevelopmental Impairment
Description
Neurodevelopmental Impairment (NDI), as assessed in a sub-population of follow-up of infants <27 wks gestation. Severe NDI will be defined by any of the following: a BSID III cognitive score < 70, Gross Motor Functional (GMF) Level of 3-5, blindness (<20/200 vision) or profound hearing loss (inability to understand commands despite amplification); moderate NDI will be defined as a BSID III cognitive score 70-84 and either a GMF level of 2 or a hearing deficit requiring amplification to understand commands or unilateral blindness; mild NDI will be defined by a cognitive score 70-84, or a cognitive score ≥ 85 and any of the following: presence of a GMF level 1 or hearing loss not requiring amplification. Normal (no NDI) will be defined by a cognitive score ≥ 85 and absence of any neurosensory deficits.
Time Frame
Birth to 26 months corrected age
Title
Number of Participants with Neurodevelopmental Impairment or Death
Description
NDI defined in outcome #9
Time Frame
Birth to 26 months corrected age

10. Eligibility

Sex
All
Minimum Age & Unit of Time
22 Weeks
Maximum Age & Unit of Time
27 Weeks
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Infants is inborn Infant is ≤ 750 grams at birth and/or < 27 weeks gestation at birth by best OB estimate Infant is 12-36 hours of age. Exclusion Criteria: Unable to enroll infant by 36 hours of age Previous phototherapy Known hemolytic disease TSB reported as >6.0 mg/dL before 12 hours age Major anomaly Overt nonbacterial infection Infant is likely to expire soon: Limiting or withdrawal of intensive care is being recommended to the parents, the parents are requesting withdrawal of care, or the pH is < 6.80 or persistent bradycardia with hypoxemia for >2h.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jon Tyson, MD
Phone
713-500-5790
Email
Jon.E.Tyson@uth.tmc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Abhik Das, PhD
Phone
301-230-4640
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jon Tyson, MD
Organizational Affiliation
The University of Texas Health Science Center, Houston
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
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
Waldemar A. Carlo, MD
Phone
205-934-4680
First Name & Middle Initial & Last Name & Degree
Waldemar A. Carlo, MD
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Krisa P. Van Meurs, MD
First Name & Middle Initial & Last Name & Degree
Krisa P. Van Meurs, MD
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30303
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ravi Patel, MD
First Name & Middle Initial & Last Name & Degree
Ravi Patel, MD
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Edward F Bell, MD
First Name & Middle Initial & Last Name & Degree
Edward F Bell
Facility Name
University of New Mexico
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kristi L. Watterberg, MD
First Name & Middle Initial & Last Name & Degree
Kristi L. Watterberg, MD
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carl T D'Angio, MD
First Name & Middle Initial & Last Name & Degree
Carl T D'Angio, MD
Facility Name
RTI International
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
C. Michael Cotten, MD
First Name & Middle Initial & Last Name & Degree
C. Michael Cotten, MD MHS
Facility Name
Cincinnati Children's Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stephanie Merhar, MD
First Name & Middle Initial & Last Name & Degree
Stephanie Merhar, MD
Facility Name
Case Western Reserve University, Rainbow Babies and Children's Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anna Maria Hibbs, MD
First Name & Middle Initial & Last Name & Degree
Anna Maria Hibbs, MD
Facility Name
Research Institute at Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pablo Sanchez, MD
First Name & Middle Initial & Last Name & Degree
Pablo Sanchez, MD
Facility Name
Univeristy of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eric Eichenwald, MD
First Name & Middle Initial & Last Name & Degree
Eric Eicenwald, MD
Facility Name
Brown University - Women and Infants Hospital of Rhode Island
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Abbot R. Laptook, MD
First Name & Middle Initial & Last Name & Degree
Abbot R Laptook, MD
Facility Name
University of Texas Southwestern Medical Center at Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Myra Myckoff, MD
First Name & Middle Initial & Last Name & Degree
Myra Myckoff, MD
Facility Name
University of Texas Health Science Center at Houston
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 MPH
First Name & Middle Initial & Last Name & Degree
Jon E. Tyson, MD MPH
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84108
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robin Ohls, MD
First Name & Middle Initial & Last Name & Degree
Robin Ohls, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
NIH has had a long-standing policy to share and make available to the public the results and accomplishments of the activities that it funds. The NRN plans to share de-identified data after final publication in an NIH supported data repository such as the NICHD Data and Specimen Hub (https://dash.nichd.nih.gov)

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Cycled Phototherapy

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