Clinical trial NCT03927833: Cycled Phototherapy
Official title: Cycled Phototherapy: A Safer Effective Method to Control the Serum Bilirubin Of Extremely Premature Infants?
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Hyper Bilirubinemia
Premature Infant
Keywords: Infant, Newborn, Diseases
Phototherapy
Lead sponsor: NICHD Neonatal Research Network
Sponsor class: NETWORK
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2019-04-25
Enrollment: 1700
Sex: ALL
Minimum age (years): 22
Maximum age (years): 27
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Pragmatic randomized clinical trial addressing patient safety.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants survival to discharge
timeFrame: Birth to hospital discharge, up to 120 days of life
Secondary outcomes:
measure: Number of hours of Phototherapy
timeFrame: Start until the end of intervention period (duration of 2 weeks)
measure: Number of irradiance hours
timeFrame: Start until the end of intervention period (duration of 2 weeks)
measure: Peak Concentration of Total Serum Bilirubin
timeFrame: Start until the end of intervention period (duration of 2 weeks)
measure: Concentration of Total Serum Bilirubin
timeFrame: Start until the end of intervention period (duration of 2 weeks)
measure: Number of Participants with Major neonatal morbidity
timeFrame: Birth to hospital discharge, up to 120 days of life
measure: Number of Participants with Severe ICH, as a component of the predischarge morbidity
timeFrame: Birth to hospital discharge, up to 120 days of life
measure: Number of Participants with Ventricular enlargement of cystic white matter disease, as a component predischarge morbidity
timeFrame: Birth to hospital discharge, up to 120 days of life
measure: Number of Participants with Bronchopulmonary dysplasia (BPD), as a component predischarge morbidity
timeFrame: Birth to hospital discharge, up to 120 days of life
measure: Number of Participants with Late onset sepsis, as a component predischarge morbidity
timeFrame: Birth to hospital discharge, up to 120 days of life
measure: Number of Participants with Necrotising enterocolitis (NEC) or spontaneous intestinal perforation, as a component predischarge morbidity
timeFrame: Birth to hospital discharge, up to 120 days of life
measure: Number of Participants with Grade 3 (or greater) retinopathy of prematurity (ROP), as a component predischarge morbidity
timeFrame: Birth to hospital discharge, up to 120 days of life
measure: Number of Participants with Patent ductus arteriosus (PDA) treated with surgery or NSAIDS
timeFrame: Birth to hospital discharge, up to 120 days of life
measure: Number of Participants with Neurodevelopmental Impairment
timeFrame: Birth to 26 months corrected age
measure: Number of Participants with Neurodevelopmental Impairment or Death
timeFrame: Birth to 26 months corrected age
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: San Diego
country: United States
facility: Sharp Mary Birch Hospital for Women & Newborns
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern Lurie Children's Hospital of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Jackson
country: United States
facility: University of Mississippi Medical Center - Children's of Mississippi
state: Mississippi
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Durham
country: United States
facility: RTI International
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University, Rainbow Babies and Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Research Institute at Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Univeristy of Pennsylvania
state: Pennsylvania
city: Providence
country: United States
facility: Brown University - Women and Infants Hospital of Rhode Island
state: Rhode Island
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Jon Tyson, MD
role: PRINCIPAL_INVESTIGATOR
References: