Cycled Phototherapy

Premature Infant Clinical Trial

Official title:

Cycled Phototherapy: A Safer Effective Method to Control the Serum Bilirubin Of Extremely Premature Infants?

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03927833
• Other study ID #: NICHD-NRN-0061
• Secondary ID: UG1HD034216UG1HD
• Status: Recruiting
• Phase: N/A
• Start date: July 15, 2020
• Est. completion date: July 2025

Study information

• Verified date: June 2024
• Source: NICHD Neonatal Research Network
• Contact: Jon Tyson, MD
• Phone: 713-500-5790
• Email: Jon.E.Tyson[@]uth.tmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Recruiting
• Enrollment: 1700
• Est. completion date: July 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 22 Weeks to 27 Weeks

Eligibility

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.

Related Conditions & MeSH terms

• Hyper Bilirubinemia
• Hyperbilirubinemia
• Premature Birth
• Premature Infant

Intervention

Device:
• Phototherapy lights
Phototherapy lights used continuously or timed, following an algorithm based upon TSB levels.

Locations

Country	Name	City	State
United States	University of New Mexico	Albuquerque	New Mexico
United States	Emory University	Atlanta	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Northwestern Lurie Children's Hospital of Chicago	Chicago	Illinois
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	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	Duke University	Durham	North Carolina
United States	RTI International	Durham	North Carolina
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	University of Mississippi Medical Center - Children's of Mississippi	Jackson	Mississippi
United States	Stanford University	Palo Alto	California
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 Rochester	Rochester	New York
United States	University of Utah	Salt Lake City	Utah
United States	Sharp Mary Birch Hospital for Women & Newborns	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
NICHD Neonatal Research Network	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants survival to discharge	Number of Participants discharged from hospital alive, after birth.	Birth to hospital discharge, up to 120 days of life
Secondary	Number of hours of Phototherapy	The reported values will be the mean total hours of phototherapy during the two week intervention period.	Start until the end of intervention period (duration of 2 weeks)
Secondary	Number of irradiance hours	The reported values will be the mean total hours of irradiance during the two week intervention period.	Start until the end of intervention period (duration of 2 weeks)
Secondary	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.	Start until the end of intervention period (duration of 2 weeks)
Secondary	Concentration of Total Serum Bilirubin	The reported values will be the mean total serum bilirubin (mg/dL) during the two week intervention period.	Start until the end of intervention period (duration of 2 weeks)
Secondary	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.	Birth to hospital discharge, up to 120 days of life
Secondary	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	Birth to hospital discharge, up to 120 days of life
Secondary	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.	Birth to hospital discharge, up to 120 days of life
Secondary	Number of Participants with Bronchopulmonary dysplasia (BPD), as a component predischarge morbidity	BPD defined as highest FiO2 at 36 wk: >0.21	Birth to hospital discharge, up to 120 days of life
Secondary	Number of Participants with Late onset sepsis, as a component predischarge morbidity	Late onset blood culture positive septicemia/bacteremia at >72 hours of age.	Birth to hospital discharge, up to 120 days of life
Secondary	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.	Birth to hospital discharge, up to 120 days of life
Secondary	Number of Participants with Grade 3 (or greater) retinopathy of prematurity (ROP), as a component predischarge morbidity	Stage 3 ROP observed in either eye.	Birth to hospital discharge, up to 120 days of life
Secondary	Number of Participants with Patent ductus arteriosus (PDA) treated with surgery or NSAIDS	PDA treated with surgery or NSAIDS (indomethacin, ibuprofen or acetaminophen)	Birth to hospital discharge, up to 120 days of life
Secondary	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.	Birth to 26 months corrected age
Secondary	Number of Participants with Neurodevelopmental Impairment or Death	NDI defined in outcome #9	Birth to 26 months corrected age