Cycled Phototherapy for Premature Infants

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

1700 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

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

What data supports the effectiveness of cycled phototherapy for premature infants?

The concept of cycled or intermittent therapy, as seen in HIV treatments, suggests potential benefits like reduced toxicity and improved quality of life, which might be applicable to cycled phototherapy for premature infants. ^{1 2 3 4 5}

How does cycled phototherapy differ from other treatments for premature infants?

Cycled phototherapy, also known as intermittent phototherapy, involves alternating periods of light exposure and darkness, which may help improve health outcomes in premature infants by mimicking natural day-night cycles. This approach is different from continuous phototherapy, which provides constant light exposure, and may offer practical benefits like improved feeding and bonding. ^{6 7 8 9 10}

What is the purpose of this trial?

Cycled phototherapy (PT) is likely to increase survival over that with continuous PT among extremely premature infants (\< 750 g BW or \<27 weeks GA).

Research Team

Jon E. Tyson, MD MPH

Principal Investigator

The University of Texas Health Science Center, Houston

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Short-cycle therapy in HIV-infected adults: rilpivirine combination 4 days on/3 days off therapy. [2022]

2. Netherlands 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]

3. United States 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. [2020]

4. England 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]

5. England pubmed.ncbi.nlm.nih.gov

Prospective randomized comparison of two prophylactic regimens with trimethoprim-sulfamethoxazole in leukemic children: a two year study. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Efficacy of phototherapy devices and outcomes among extremely low birth weight infants: multi-center observational study. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy of Intermittent Phototherapy versus Continuous Phototherapy for Treatment of Neonatal Hyperbilirubinaemia: A Systematic Review and Meta-analysis. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Effect of phototherapy in preterm infants on growth in the neonatal period. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Intermittent phototherapy versus continuous phototherapy for neonatal jaundice. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Timing for the Introduction of Cycled Light for Extremely Preterm Infants: A Randomized Controlled Trial. [2018]