Hyper BilirubinemiaNCT03927833
Cycled Phototherapy
A study testing Phototherapy lights in people with Hyper Bilirubinemia and Premature Infant, run by NICHD Neonatal Research Network at 19 sites in United States.
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). Read more about this study
- Who is it for?
- Ages 22 to 27 weeks
- Conditions the study is for
- Hyper Bilirubinemia, Premature Infant
- What is being tested?
- Phototherapy lights
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,700 participants
- Where
- 19 sitesUnited States
- Study dates
- 16 Jul 2020to 31 Jul 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 to 27 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
United States19 sites
University of New Mexico
Albuquerque, New Mexico, 87131
Emory University
Atlanta, Georgia, 30303
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Northwestern Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Cincinnati Children's Medical Center
Cincinnati, Ohio, 45267
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, 44106
Research Institute at Nationwide Children's Hospital
Columbus, Ohio, 43205
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75235
RTI International
Durham, North Carolina, 27705
Duke University
Durham, North Carolina, 27710
University of Texas Health Science Center at Houston
Houston, Texas, 77030
University of Iowa
Iowa City, Iowa, 52242
University of Mississippi Medical Center - Children's of Mississippi
Jackson, Mississippi, 39216
Stanford University
Palo Alto, California, 94304
Univeristy of Pennsylvania
Philadelphia, Pennsylvania, 19104
Brown University - Women and Infants Hospital of Rhode Island
Providence, Rhode Island, 02905
University of Rochester
Rochester, New York, 14642
University of Utah
Salt Lake City, Utah, 84108
Sharp Mary Birch Hospital for Women & Newborns
San Diego, California, 92123
About this study
Official title: Cycled Phototherapy: A Safer Effective Method to Control the Serum Bilirubin Of Extremely Premature Infants?
Cycled phototherapy (PT) is likely to increase survival over that with continuous PT among extremely premature infants (< 750 g BW or <27 weeks GA).
Read the 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.
- Conditions
- Hyper Bilirubinemia, Premature Infant
- Being tested
- Phototherapy lights
- Keywords
- Infant, Newborn, Diseases, Phototherapy
- Medical subject headings
- Premature Birth, Infant, Newborn, Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Phototherapy lightsDevice
Phototherapy lights used continuously or timed, following an algorithm based upon TSB levels.
| Study group | Role | What they receive |
|---|---|---|
| Continuous Phototherapy | Active comparator | Continuous phototherapy Receives: Device: Phototherapy lights |
| Cycled Phototherapy | Experimental | Cycled phototherapy at timed intervals, dependent upon total serum bilirum (TSB) levels. Receives: Device: Phototherapy lights |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants survival to discharge
Number of Participants discharged from hospital alive, after birth.
Measured: Birth to hospital discharge, up to 120 days of life
Secondary outcomes (14)
Number of hours of Phototherapy
The reported values will be the mean total hours of phototherapy during the two week intervention period.
Measured: Start until the end of intervention period (duration of 2 weeks)
Number of irradiance hours
The reported values will be the mean total hours of irradiance during the two week intervention period.
Measured: Start until the end of intervention period (duration of 2 weeks)
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.
Measured: Start until the end of intervention period (duration of 2 weeks)
Concentration of Total Serum Bilirubin
The reported values will be the mean total serum bilirubin (mg/dL) during the two week intervention period.
Measured: Start until the end of intervention period (duration of 2 weeks)
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.
Measured: Birth to hospital discharge, up to 120 days of life
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
Measured: Birth to hospital discharge, up to 120 days of life
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.
Measured: Birth to hospital discharge, up to 120 days of life
Number of Participants with Bronchopulmonary dysplasia (BPD), as a component predischarge morbidity
BPD defined as highest FiO2 at 36 wk: >0.21
Measured: Birth to hospital discharge, up to 120 days of life
Number of Participants with Late onset sepsis, as a component predischarge morbidity
Late onset blood culture positive septicemia/bacteremia at >72 hours of age.
Measured: Birth to hospital discharge, up to 120 days of life
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.
Measured: Birth to hospital discharge, up to 120 days of life
Number of Participants with Grade 3 (or greater) retinopathy of prematurity (ROP), as a component predischarge morbidity
Stage 3 ROP observed in either eye.
Measured: Birth to hospital discharge, up to 120 days of life
Number of Participants with Patent ductus arteriosus (PDA) treated with surgery or NSAIDS
PDA treated with surgery or NSAIDS (indomethacin, ibuprofen or acetaminophen)
Measured: Birth to hospital discharge, up to 120 days of life
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.
Measured: Birth to 26 months corrected age
Number of Participants with Neurodevelopmental Impairment or Death
NDI defined in outcome #9
Measured: Birth to 26 months corrected age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2019
- Study start16 Jul 2020
- Primary completion4 Nov 2025
- Study completion31 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hyper BilirubinemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Pragmatic randomized clinical trial addressing patient safety.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 1,700 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NICHD Neonatal Research Network
- Sponsor type
- Research network
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Jon Tyson, MD, Principal investigator, The University of Texas Health Science Center, Houston
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03927833
- Sponsor's protocol ID
- NICHD-NRN-0061
- Other IDs
- UG1HD034216, UG1HD027904, UG1HD021364, UG1HD027853, UG1HD040689, UG1HD040492, UG1HD027851, UG1HD087229
- Status last verified
- Dec 2025
- First submitted
- 18 Apr 2019
- Last updated
- 17 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: 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)
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cycled Phototherapy: A Safer Effective Method to Control the Serum Bilirubin Of Extremely Premature Infants?
- ClinicalTrials.gov ID
- NCT03927833
- Acronym / sponsor ID
- NICHD-NRN-0061
- Conditions
- Hyper Bilirubinemia, Premature Infant
- Keywords
- Infant, Newborn, Diseases, Phototherapy
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 1,700 participants (estimated)
- Lead sponsor
- NICHD Neonatal Research NetworkResearch network
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 16 Jul 2020 (actual)
- Primary completion
- 4 Nov 2025 (actual)
- Study completion
- 31 Jul 2027 (estimated)
- First posted
- 25 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Pragmatic randomized clinical trial addressing patient safety.
| Arm | Type | Receives |
|---|---|---|
| Continuous Phototherapy | Active comparator | Device: Phototherapy lightsContinuous phototherapy |
| Cycled Phototherapy | Experimental | Device: Phototherapy lightsCycled phototherapy at timed intervals, dependent upon total serum bilirum (TSB) levels. |
Who may qualify
- Ages
- 22 to 27 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Phototherapy lightsPhototherapy lights used continuously or timed, following an algorithm based upon TSB levels. | Device | Continuous Phototherapy, Cycled Phototherapy |
Primary outcome
Number of participants survival to discharge
Time frame: Birth to hospital discharge, up to 120 days of life
Number of Participants discharged from hospital alive, after birth.
14 secondary outcomes
Number of hours of Phototherapy
Time frame: Start until the end of intervention period (duration of 2 weeks)
Number of irradiance hours
Time frame: Start until the end of intervention period (duration of 2 weeks)
Peak Concentration of Total Serum Bilirubin
Time frame: Start until the end of intervention period (duration of 2 weeks)
Concentration of Total Serum Bilirubin
Time frame: Start until the end of intervention period (duration of 2 weeks)
Number of Participants with Major neonatal morbidity
Time frame: Birth to hospital discharge, up to 120 days of life
Number of Participants with Severe ICH, as a component of the predischarge morbidity
Time frame: Birth to hospital discharge, up to 120 days of life
Number of Participants with Ventricular enlargement of cystic white matter disease, as a component predischarge morbidity
Time frame: Birth to hospital discharge, up to 120 days of life
Number of Participants with Bronchopulmonary dysplasia (BPD), as a component predischarge morbidity
Time frame: Birth to hospital discharge, up to 120 days of life
Number of Participants with Late onset sepsis, as a component predischarge morbidity
Time frame: Birth to hospital discharge, up to 120 days of life
Number of Participants with Necrotising enterocolitis (NEC) or spontaneous intestinal perforation, as a component predischarge morbidity
Time frame: Birth to hospital discharge, up to 120 days of life
Number of Participants with Grade 3 (or greater) retinopathy of prematurity (ROP), as a component predischarge morbidity
Time frame: Birth to hospital discharge, up to 120 days of life
Number of Participants with Patent ductus arteriosus (PDA) treated with surgery or NSAIDS
Time frame: Birth to hospital discharge, up to 120 days of life
Number of Participants with Neurodevelopmental Impairment
Time frame: Birth to 26 months corrected age
Number of Participants with Neurodevelopmental Impairment or Death
Time frame: Birth to 26 months corrected age
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2026.
- Individual participant dataSharing planned: Yes. 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)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jon Tyson, MD principal investigator
The University of Texas Health Science Center, Houston
19 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Phototherapy lights in people with Hyper Bilirubinemia and Premature Infant, run by NICHD Neonatal Research Network at 19 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 17 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants survival to discharge (time frame: Birth to hospital discharge, up to 120 days of life). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2026.