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

NCT ID: NCT07110987

Last Updated: 2025-12-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-06-26

Study Completion Date

2027-03-01

Brief Summary

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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.

Detailed Description

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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:

1. Hemolytic jaundice (ABO or Rh incompatibility)
2. Non-hemolytic jaundice (physiological or breast milk)
3. 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.

Conditions

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Hyperbilirubinemia, Neonatal Indirect

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Group A - phototherapy only

Infants who have indirect hyperbilirubinemia recieve continuous triple phototherapy only .

Group Type ACTIVE_COMPARATOR

Phototherapy

Intervention Type PROCEDURE

Triple continuous phototherapy per AAP Guudelines

Group B - phototherapy + UDCA

Phototherapy + UDCA

Group Type EXPERIMENTAL

Phototherapy

Intervention Type PROCEDURE

Triple continuous phototherapy per AAP Guudelines

ursodeoxycholic acid (UDCA)

Intervention Type 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.

Interventions

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Phototherapy

Triple continuous phototherapy per AAP Guudelines

Intervention Type PROCEDURE

ursodeoxycholic acid (UDCA)

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.

Intervention Type DRUG

Other Intervention Names

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Triple continuous phototherapy Ursodiol UDCA

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

1. Gestational age \< 34 weeks
2. Small or Large for Gestational Age
3. Direct (conjugated) hyperbilirubinemia \> 20% of total bilirubin
4. Suspected or confirmed sepsis
5. Neonates of diabetic mothers
6. Presence of congenital or acquired liver disease
7. Receiving Total Parenteral Nutrition (TPN)
Maximum Eligible Age

1 Month

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Tishreen University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Ashraf Maan Alshelly

MD, Pediatric Resident

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Adnan H Dayoub, Prof.Neonat

Role: STUDY_DIRECTOR

Lattakia university hospital (Tishreen university Hospital ) , Lattakia university

Locations

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Lattakia University Hospital

Latakia, , Syria

Site Status RECRUITING

Countries

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Syria

Central Contacts

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Ashraf M Alshelly, MD, Ped.Res.

Role: CONTACT

+963930052903

Facility Contacts

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Alshelly

Role: primary

+963930052903

References

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Rodrigues CM, Steer CJ. The therapeutic effects of ursodeoxycholic acid as an anti-apoptotic agent. Expert Opin Investig Drugs. 2001 Jul;10(7):1243-53. doi: 10.1517/13543784.10.7.1243.

Reference Type BACKGROUND
PMID: 11772248 (View on PubMed)

2. Wang H, et al. Effect of ursodeoxycholic acid on neonatal indirect hyperbilirubinemia: A meta-analysis. World J Pediatr. 2022;18(5):375-383. PMID: 35689782

Reference Type RESULT

3. Hassan NM, El Said NM. Role of ursodeoxycholic acid in treatment of neonatal indirect hyperbilirubinemia. Iraqi J Pediatr. 2015;32(1):42-47.

Reference Type RESULT

Ughasoro MD, Adimorah GN, Chukwudi NK, Nnakenyi ID, Iloh KK, Udemba CE. Reductive effect of ursodeoxycholic acid on bilirubin levels in neonates on phototherapy. Clin Exp Gastroenterol. 2019 Jul 29;12:349-354. doi: 10.2147/CEG.S207523. eCollection 2019.

Reference Type RESULT
PMID: 31534356 (View on PubMed)

Rezaie M, Gholami R, Jafari M, Haghighinejad H. Evaluating the effect of ursodeoxycholic acid on total bilirubin of neonates with glucose-6-phosphate dehydrogenase deficiency complicated by indirect hyperbilirubinaemia. J Paediatr Child Health. 2021 Aug;57(8):1175-1181. doi: 10.1111/jpc.15411. Epub 2021 Mar 8.

Reference Type RESULT
PMID: 33682983 (View on PubMed)

Related Links

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https://pubmed.ncbi.nlm.nih.gov/35689782/

PubMed - Meta-analysis on UDCA in neonates

Other Identifiers

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Alshelly-UDCA-2025

Identifier Type: -

Identifier Source: org_study_id

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