Cycled Phototherapy for Premature Infants

Not currently recruiting at 18 trial locations

Overseen By Jon Tyson, MD

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: NICHD Neonatal Research Network

Disqualifiers: Hemolytic disease, Major anomaly, Nonbacterial infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how cycled phototherapy (light treatment given at specific intervals) benefits extremely premature infants compared to continuous phototherapy. The researchers aim to determine if cycled phototherapy can improve survival rates for babies born weighing less than 750 grams (about 1.65 pounds) or before 27 weeks of pregnancy. Babies who might qualify for this trial are those born very early or with very low birth weight, and they need to be enrolled within 12 to 36 hours after birth. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance care for future premature infants.

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications.

What prior data suggests that cycled phototherapy is safe for premature infants?

Research has shown that cycled phototherapy, a light treatment for very premature babies, is generally safe when used correctly. This treatment helps lower bilirubin levels, which is crucial for preventing jaundice in newborns. Studies have found that cycled phototherapy is effective without increasing the risk of harm compared to continuous phototherapy.

Additionally, research suggests that babies receiving cycled phototherapy spend less time under the light than those receiving continuous phototherapy. This reduction in exposure may help minimize potential side effects from prolonged light exposure. The available data has not reported any major serious problems directly linked to cycled phototherapy. However, it is important to remember that each baby is different, and their reactions to treatment can vary. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about cycled phototherapy for premature infants because it offers a potentially more personalized approach to treating high bilirubin levels, a common issue in these newborns. Unlike continuous phototherapy, which is a standard treatment that delivers constant light exposure, cycled phototherapy adjusts the light exposure based on the infant's total serum bilirubin (TSB) levels. This tailored method could minimize unnecessary light exposure, potentially reducing stress and side effects for the infant. By optimizing the timing of the light treatment, this approach might improve outcomes and comfort for premature infants compared to the current standard of care.

What evidence suggests that cycled phototherapy might be an effective treatment for premature infants?

This trial will compare cycled phototherapy with continuous phototherapy for managing bilirubin levels in premature infants. Research has shown that cycled phototherapy, where light treatment is given in breaks, can be as effective as continuous phototherapy in lowering bilirubin levels. Studies have found that both methods effectively reduce bilirubin, which can cause jaundice, without major differences in the speed of reduction. Early results suggest that cycled phototherapy might offer the same benefits with potentially less light exposure, which could be safer for the babies. Although a large, randomized trial is needed to confirm these findings, current evidence supports the potential effectiveness of cycled phototherapy in managing bilirubin levels in extremely premature infants. ^{1 4 6 7 8}

Who Is on the Research Team?

Jon E. Tyson, MD MPH

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for extremely premature infants who weigh ≤ 750 grams or are born before 27 weeks of gestation. They must be between 12-36 hours old and born at the hospital conducting the study. Infants with previous phototherapy, certain blood conditions, infections, major anomalies, or those critically ill aren't eligible.

Inclusion Criteria

Infant is ≤ 750 grams at birth and/or < 27 weeks gestation at birth by best OB estimate

The study does not include newborn babies.

My baby is between 12 to 36 hours old.

Exclusion Criteria

TSB reported as >6.0 mg/dL before 12 hours age

I have undergone phototherapy before.

The infant is very sick and may not survive much longer. The doctors have recommended limiting or stopping care, or the parents have asked to stop care. The infant's blood is not carrying enough oxygen and their heart rate is too slow for more than two hours.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either cycled or continuous phototherapy based on randomization

2 weeks

Daily monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 120 days

Long-term follow-up

Participants are assessed for neurodevelopmental impairment

Up to 26 months corrected age

What Are the Treatments Tested in This Trial?

Interventions

• Cycled Phototherapy

Trial Overview The trial is testing if cycled phototherapy (turning lights on and off) improves survival rates in these tiny babies compared to continuous light exposure. It's focused on very small preemies who often face health challenges due to early birth.

How Is the Trial Designed?

Group I: Cycled Phototherapy Experimental Treatment 1 Intervention

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

Group II: Continuous Phototherapy Active Control 1 Intervention

Continuous phototherapy

Cycled Phototherapy is already approved in United States, European Union for the following indications:

Approved in United States as Cycled Phototherapy for:

• Neonatal jaundice (hyperbilirubinemia) in extremely low birth weight infants

Approved in European Union as Intermittent Phototherapy for:

• Neonatal jaundice (hyperbilirubinemia) in preterm infants

Who Is Running the Clinical Trial?

NICHD Neonatal Research Network

Lead Sponsor

Trials

62

Recruited

209,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

Intermittent phototherapy is as effective as continuous phototherapy for treating neonatal hyperbilirubinaemia, based on a meta-analysis of four studies involving 716 neonates.

Intermittent phototherapy is associated with shorter treatment duration and fewer side effects compared to continuous phototherapy, making it a safer option for infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Intermittent Phototherapy versus Continuous Phototherapy for Treatment of Neonatal Hyperbilirubinaemia: A Systematic Review and Meta-analysis. Chu, L., Xue, X., Qiao, J.[2021]

A systematic review of 12 randomized controlled trials involving 1600 infants found little to no difference in the effectiveness of intermittent versus continuous phototherapy for reducing bilirubin levels in jaundiced newborns.

While intermittent phototherapy may offer practical advantages, such as reduced total hours of exposure, the safety outcomes, particularly regarding bilirubin-induced brain dysfunction, remain uncertain and require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent phototherapy versus continuous phototherapy for neonatal jaundice. Gottimukkala, SB., Lobo, L., Gautham, KS., et al.[2023]

In a study of 1404 extremely premature infants, phototherapy using light-emitting diodes (LEDs) resulted in the greatest initial reduction in total serum bilirubin (TSB) levels compared to other devices, with a mean decrease of 2.2 mg/dl in the first 24 hours.

While LEDs were most effective initially, other devices like spotlights showed similar performance in long-term outcomes, indicating the need for further research on the long-term effects of different phototherapy devices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of phototherapy devices and outcomes among extremely low birth weight infants: multi-center observational study. Morris, BH., Tyson, JE., Stevenson, DK., et al.[2022]

A meta-analysis of 26 trials involving 37,298 women showed that dose-intense chemotherapy (administered every 2 weeks) significantly reduced the 10-year risk of breast cancer recurrence (28.0% vs 31.4%) and mortality (18.9% vs 21.3%) compared to standard 3-week schedules.

The study found that increasing dose intensity, whether by shortening treatment intervals or using sequential drug administration, effectively lowers the risk of recurrence and death from breast cancer without increasing the risk of death from other causes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials. [2023]

Extremely preterm infants (≤28 weeks gestation) who received early cycled light (ECL) showed a trend towards improved weight gain compared to those who received late cycled light (LCL), with mean weight gain of 193.8 grams in the ECL group versus 176.3 grams in the LCL group during specific postmenstrual age weeks.

Infants in the ECL group were discharged from the hospital an average of 5.5 days earlier than those in the LCL group, suggesting potential benefits of early cycled light on hospital stay, although this difference was not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Timing for the Introduction of Cycled Light for Extremely Preterm Infants: A Randomized Controlled Trial. Brandon, DH., Silva, SG., Park, J., et al.[2018]

A once-daily short-cycle structured intermittent therapy (SIT) regimen effectively maintained suppression of plasma HIV RNA in 7 out of 8 patients for 60-84 weeks, demonstrating its potential as a viable treatment option.

The regimen preserved CD4(+) T cell counts and did not significantly alter liver enzyme or lipid levels, suggesting it is a safe alternative to continuous antiretroviral therapy, especially in resource-limited settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A proof-of-concept study of short-cycle intermittent antiretroviral therapy with a once-daily regimen of didanosine, lamivudine, and efavirenz for the treatment of chronic HIV infection. Dybul, M., Nies-Kraske, E., Dewar, R., et al.[2020]

In a study involving 199 HIV-1-infected young people, short cycle therapy (5 days on, 2 days off ART) was found to be non-inferior to continuous therapy in maintaining viral suppression over 48 weeks, with only 6% of participants in the short cycle group experiencing viral loads above 50 copies per mL.

Short cycle therapy demonstrated a better safety profile, with significantly fewer ART-related adverse events compared to continuous therapy (2 vs. 14 events), making it a promising option for young patients stable on efavirenz-based ART.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekends-off efavirenz-based antiretroviral therapy in HIV-infected children, adolescents, and young adults (BREATHER): a randomised, open-label, non-inferiority, phase 2/3 trial. [2021]

In a study of 120 preterm infants, those receiving continuous and intermittent phototherapy showed slower weight gain in the first week compared to the control group, with only 44% and 57.6% regaining birth weight, respectively, versus 80% in controls.

However, by weeks 2 and 3, both phototherapy groups exhibited greater weight gain than the control group, suggesting that while phototherapy may initially hinder growth, it can lead to catch-up growth later on.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of phototherapy in preterm infants on growth in the neonatal period. Wu, PY., Lim, RC., Hodgman, JE., et al.[2019]

In a study of HIV-infected adults on a short-cycle therapy (SCT) regimen with rilpivirine, 100% of participants maintained virological suppression after 48 weeks, demonstrating the efficacy of this treatment approach.

The SCT regimen also resulted in high patient satisfaction (average score of 57.7/60) and no adverse events, suggesting it is a safe and effective alternative to continuous therapy for selected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-cycle therapy in HIV-infected adults: rilpivirine combination 4 days on/3 days off therapy. Luise, D., Lattuada, E., Rizzardo, S., et al.[2022]

In a study involving children with acute hematologic malignancies, both continuous and intermittent prophylaxis with trimethoprim-sulfamethoxazole showed similar effectiveness in preventing severe infections, with 17 infections in the continuous group and 21 in the intermittent group.

The side effects were also comparable between the two regimens, suggesting that neither approach is superior in terms of safety or efficacy, allowing decisions to be made based on cost and patient preference.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective randomized comparison of two prophylactic regimens with trimethoprim-sulfamethoxazole in leukemic children: a two year study. Rossi, MR., Banfi, P., Cappuccilli, M., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7186919/

Cycled Phototherapy Dose-Finding Study for Extremely Low ... A large, randomized trial is needed to assess whether cycled phototherapy would increase survival and survival without impairment in small, preterm infants.

2. publications.aap.org publications.aap.org/pediatrics/article/154/3/e2024068026/199038/Phototherapy-to-Prevent-Severe-Neonatal

Phototherapy to Prevent Severe Neonatal ... With proper administration of effective phototherapy to an infant without concurrent hemolysis, total serum or plasma bilirubin concentrations will decrease.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0377123725001091

Original Article Intermittent phototherapy vs continuous ... Intermittent phototherapy (with 12 hours on and 12 hours off cycles), along with clinical and lab monitoring was as effective as continuous phototherapy.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9979775/

Intermittent phototherapy versus continuous ... - PubMed Central The available evidence detected little or no difference between intermittent and continuous phototherapy with respect to rate of decline of bilirubin.

5. cochranelibrary.com cochranelibrary.com/cdsr/doi/10.1002/14651858.CD008168.pub2/references

Intermittent phototherapy versus continuous ... Primary outcomes reported did not match primary and secondary outcomes in trial registry. NCT01944696: Cycled phototherapy: a safer effective treatment for ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03927833

Study Details | NCT03927833 | Cycled Phototherapy Were they not delivered early, extremely premature infants would normally develop in darkness within the uterus for 3-4 more months longer before birth.

7. med.uth.edu med.uth.edu/pediatrics/cycled-phototherapy-study/

Cycled Phototherapy Study (CPT) - McGovern Medical School The Cycled Phototherapy Study aims to compare two different doses of phototherapy (continuous and cycled) in extremely preterm infants.

8. pm.amegroups.org pm.amegroups.org/article/view/6323/html

Phototherapy for preterm newborns—historical controversies ... Cycled phototherapyOther Section​​ Among newborns surviving 14 days, 128 treated with cycled phototherapy were exposed to 34±19 hours of phototherapy versus 72± ...