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NCT Number: NCT07110987

The Efficacy of Ursodeoxycholic Acid (UDCA) as Adjuvant Therapy to Phototherapy in the Management of Neonatal Indirect Hyperbilirubinemia

This is a prospective, open-label, randomized controlled trial conducted at Lattakia University Hospital (Tishreen University), aiming to evaluate the efficacy of Ursodeoxycholic Acid (UDCA) as an adjuvant to triple phototherapy in the management of indirect hyperbilirubinemia in neonates ≥34 weeks of gestation.

Eligible neonates will be randomly assigned to one of two groups:

Group A: continuous triple phototherapy only

Group B: UDCA (10 mg/kg/day in two oral doses) in addition to triple continuous phototherapy.

Stratified randomization will be applied according to etiology (hemolytic, non-hemolytic, G6PD deficiency). The primary outcome is the rate and time of decline in total and indirect serum bilirubin to below phototherapy thresholds, monitored every 12 hours until discharge.

This trial seeks to determine whether UDCA may reduce phototherapy duration or enhance bilirubin clearance in a safe and effective manner.

Although this is an open-label trial for care providers and participants , the statstican conducting data analysis will be blinded to group allocation to reduce assessment bias.

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Key information

Conditions

Hyperbilirubinemia, Neonatal Indirect Anemia Anemia, Hemolytic Anemia, Hemolytic, Congenital Carbohydrate Metabolism, Inborn Errors Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Glucosephosphate Dehydrogenase Deficiency Hematologic Diseases Hemic and Lymphatic Diseases Hyperbilirubinemia Hyperbilirubinemia, Neonatal Infant, Newborn, Diseases Metabolic Diseases Metabolism, Inborn Errors Nutritional and Metabolic Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

Up to 1 month

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Lattakia University Hospital

Latakia, 0000, Syria

Location status: Recruiting

Location contact

Adnan H Dayoub, Prof.Neonat

SUB_INVESTIGATOR

Alshelly

CONTACT

[email protected]

+963930052903

Ashraf M Alshelly, MD, Ped.Res.

PRINCIPAL_INVESTIGATOR

About this study

This is a prospective, open-label, randomized controlled clinical trial designed to assess the efficacy of ursodeoxycholic acid (UDCA) as an adjuvant to continuous triple phototherapy in neonates with indirect hyperbilirubinemia.

The study includes neonates ≥34 weeks gestational age and appropriate for gestational age (AGA), who meet the American Academy of Pediatrics (AAP) criteria for starting phototherapy.

Participants will be randomized 1:1 into two parallel arms:

Group A (Control): Continuous triple phototherapy

Group B (Intervention): Continuous triple phototherapy + oral UDCA at a dose of 10 mg/kg/day divided into two doses, using locally available Ursorasha (Rasha Pharma, license #1991/1192).

Randomization will be performed using stratified block randomization, with three stratification layers to balance known confounding factors across groups:

  • Hemolytic jaundice (ABO or Rh incompatibility)
  • Non-hemolytic jaundice (physiological or breast milk)
  • G6PD deficiency

Total serum bilirubin (TSB) will be monitored every 12 hours and compared across groups. Primary outcome is the time needed for bilirubin to drop below phototherapy threshold, according to age-specific AAP phototherapy nomograms.

Additional secondary analyses will include the rate of bilirubin decline at 24 and 48 hours, need for rescue therapy, and subgroup analysis based on gestational age (late preterm vs term), and jaundice type.

Based on retrospective hospital data, the anticipated enrollment is 70 neonates. However, due to the lower prevalence of G6PD deficiency, this subgroup may not yield enough cases for statistically powered subgroup analysis. It will instead be analyzed descriptively or as exploratory.

The study includes clearly defined inclusion/exclusion criteria and a unified therapeutic protocol applied to all infants.

Inclusion criteria

Neonates ≥34 weeks GA, AGA, with indirect hyperbilirubinemia requiring phototherapy.

Exclusion criteria

Neonates <34 weeks, non-AGA, suspected/confirmed sepsis, TPN, liver disorders, or infants of diabetic mothers.

This protocol was initiated and registered within 21 days of enrolling the first patient. The study has received initial approval from the Department of Pediatrics at Lattakia University Hospital (formerly Tishreen University Hospital) under Committee Decision #70. Final administrative ethics approval from the university is in progress due to procedural delays in our country.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Neonates with gestational age ≥ 34 weeks
  • Appropriate for Gestational Age (AGA) infants
  • Presence of indirect hyperbilirubinemia that meets the threshold for phototherapy.

Exclusion criteria

  • Gestational age < 34 weeks
  • Small or Large for Gestational Age
  • Direct (conjugated) hyperbilirubinemia > 20% of total bilirubin
  • Suspected or confirmed sepsis
  • Neonates of diabetic mothers
  • Presence of congenital or acquired liver disease
  • Receiving Total Parenteral Nutrition (TPN)

Treatment and study plan

Phototherapy

Procedure

Triple continuous phototherapy per AAP Guudelines

Other names: Triple continuous phototherapy

Ursodeoxycholic acid (UDCA)

Drug

10mg/kg/day orally divided in two doses (URSORASHA) . Given with feeds untill the bilirubin level drop down to limits that don't need therapy due to AAP guidelines.

Other names: Ursodiol, UDCA

Primary outcomes

  1. Reduction of total serum bilirubin to below phototherapy threshold

    Time frame: Day 0 to Day 7

    Measurement of serum total bilirubin levels every 12 hours until they fall below the phototherapy threshold based on gestational age and postnatal age. Outcome is considered achieved once bilirubin levels drop below threshold and phototherapy can be discontinued .

  2. Time to bilirubin reduction below treatment threshold

    Time frame: Day 0 to Day 7

    Time (in hours) from treatment initiation to TSB falling below phototherapy threshold in each group.

  3. Mean reduction in total serum bilirubin at 12 hours

    Time frame: 12 hours of starting therapy

    To compare the average decrease in total serum bilirubin after 12 hours between the two groups.

Secondary outcomes

  1. Comparison of Hospital stay between both groups

    Time frame: Day 0 to Day 7

    The total length of hospital stay (in days) will be compared between both groups (phototherapy alone and UDCA + phototherapy) to assess the impac5 of UDCA on hospital stay duration.

  2. Comparison of bilirubin reduction between late preterm (34weeks-36weeks+6 days) and term infants (≥37 weeks) in each treatment group.

    Time frame: Up to 7 Days

    This outcome aims to evaluate whether the gestational maturity of neonates affects the response to the assigned treatment. The kinetics of bilirubin reduction (mg/dL over time) will be analyzed separately within the phototherapy-only group and the phototherapy + UDCA group, comparing late preterm and term neonates.

  3. Comparison of bilirubin decline in each gestational age group (preterm vs preterm) and (term vs term) across jaundice types between treatment arms.

    Time frame: Day 0 to Day 7.

    This outcome investigates whether the effectiveness of UDCA as an adjuvant varies by both gestational age and jaundice type. Within each gestational age group (late preterm and term), the bilirubin decline trends in rate (mg/dl) will be compared between the treatment groups across each of the following etiologies:

    • Hemolytic jaundice
    • Non-hemolytic jaundice
    • G6PD-related jaundice

  4. Need for retreatment

    Time frame: Day 0 to Day 10 , Up to 3 days after treatment discontinuation.

    percentage of infants who required re-initiation of phototherapy after initial discontinuation in each Arm .

  5. Incidence of adverse effects in the UDCA group

    Time frame: Day 0 to Day 7

    Any reported side effects in neonates receiving UDCA

  6. Time to bilirubin reduction below threshold between treatment groups within each gestational age category

    Time frame: Up to 7 Days

    Time from initiation of treatment to bilirubin falling below treatment threshold for:

    • Late preterm (34-36+6 weeks): Group A vs. Group B
    • Term (≥37 weeks): Group A vs. Group B

  7. Time to bilirubin reduction between late preterm and term neonates within each treatment group

    Time frame: Up to 7 Days

    To assess whether gestational age affects time to bilirubin normalization within each group.

  8. Time to bilirubin normalization in each gestational age group across jaundice types

    Time frame: Up to 7 Days.

    For each gestational age (late preterm, term), compare time to normalization among jaundice types (hemolytic, non-hemolytic, G6PD) between groups.

Study contacts

Contact information is provided by the study sponsor or research team.

Ashraf M Alshelly, MD, Ped.Res.

CONTACT

[email protected]

+963930052903

Sponsors and collaborators

Lead sponsor

Tishreen University Hospital

Other

Registry information

Official study title

A Prospective Open-label Randomized Controlled Trial , Evaluating the Efficacy of Ursodeoxycholic Acid (UDCA) as an Adjuvant to Phototherapy in Neonates With Indirect Hyperbilirubinemia

Acronym: UDCA-Neo

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Aug 8, 2025
Registry last updated
Apr 21, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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