Cycled Phototherapy
- Conditions
- Hyper BilirubinemiaPremature Infant
- Interventions
- Device: Phototherapy lights
- Registration Number
- NCT03927833
- Lead Sponsor
- NICHD Neonatal Research Network
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1700
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Continuous Phototherapy Phototherapy lights Continuous phototherapy Cycled Phototherapy Phototherapy lights Cycled phototherapy at timed intervals, dependent upon total serum bilirum (TSB) levels.
- Primary Outcome Measures
Name Time Method Number of participants survival to discharge Birth to hospital discharge, up to 120 days of life Number of Participants discharged from hospital alive, after birth.
- Secondary Outcome Measures
Name Time Method Number of hours of Phototherapy Start until the end of intervention period (duration of 2 weeks) The reported values will be the mean total hours of phototherapy during the two week intervention period.
Number of Participants with Major neonatal morbidity Birth to hospital discharge, up to 120 days of life 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 irradiance hours Start until the end of intervention period (duration of 2 weeks) The reported values will be the mean total hours of irradiance during the two week intervention period.
Number of Participants with Bronchopulmonary dysplasia (BPD), as a component predischarge morbidity Birth to hospital discharge, up to 120 days of life BPD defined as highest FiO2 at 36 wk: \>0.21
Number of Participants with Ventricular enlargement of cystic white matter disease, as a component predischarge morbidity Birth to hospital discharge, up to 120 days of life 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 Late onset sepsis, as a component predischarge morbidity Birth to hospital discharge, up to 120 days of life Late onset blood culture positive septicemia/bacteremia at \>72 hours of age.
Peak Concentration of Total Serum Bilirubin Start until the end of intervention period (duration of 2 weeks) The reported values will be the mean peak total serum bilirubin (mg/dL) during the two week intervention period.
Number of Participants with Patent ductus arteriosus (PDA) treated with surgery or NSAIDS Birth to hospital discharge, up to 120 days of life PDA treated with surgery or NSAIDS (indomethacin, ibuprofen or acetaminophen)
Number of Participants with Neurodevelopmental Impairment Birth to 26 months corrected age 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.
Concentration of Total Serum Bilirubin Start until the end of intervention period (duration of 2 weeks) The reported values will be the mean total serum bilirubin (mg/dL) during the two week intervention period.
Number of Participants with Severe ICH, as a component of the predischarge morbidity Birth to hospital discharge, up to 120 days of life 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 Necrotising enterocolitis (NEC) or spontaneous intestinal perforation, as a component predischarge morbidity Birth to hospital discharge, up to 120 days of life 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 Birth to hospital discharge, up to 120 days of life Stage 3 ROP observed in either eye.
Number of Participants with Neurodevelopmental Impairment or Death Birth to 26 months corrected age NDI defined in outcome #9
Trial Locations
- Locations (19)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Stanford University
🇺🇸Palo Alto, California, United States
Sharp Mary Birch Hospital for Women & Newborns
🇺🇸San Diego, California, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Northwestern Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
University of Mississippi Medical Center - Children's of Mississippi
🇺🇸Jackson, Mississippi, United States
University of New Mexico
🇺🇸Albuquerque, New Mexico, United States
University of Rochester
🇺🇸Rochester, New York, United States
RTI International
🇺🇸Durham, North Carolina, United States
Duke University
🇺🇸Durham, North Carolina, United States
Cincinnati Children's Medical Center
🇺🇸Cincinnati, Ohio, United States
Case Western Reserve University, Rainbow Babies and Children's Hospital
🇺🇸Cleveland, Ohio, United States
Research Institute at Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Univeristy of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Brown University - Women and Infants Hospital of Rhode Island
🇺🇸Providence, Rhode Island, United States
University of Texas Southwestern Medical Center at Dallas
🇺🇸Dallas, Texas, United States
University of Texas Health Science Center at Houston
🇺🇸Houston, Texas, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States