Adjuvant Ursodeoxycholic Acid Therapy in Neonates Undergoing Phototherapy for Hyperbilirubinemia: A Randomized Controlled Trial

To evaluate the effect of adjunctive ursodeoxycholic acid on serum bilirubin reduction and duration of phototherapy in neonates with indirect hyperbilirubinemia.

Single-blind, parallel-group randomized controlled trial with 1:1 allocation. Based on the study by Akefi et al., and considering a significance level of α = 0.05 (type I error) and a power of 1−β = 0.95, the required sample size was calculated to be 128 participants per group. Taking into account a 5% potential dropout rate, the final sample size was determined to be 134 participants per group.

Neonatal and NICU departments of hospitals affiliated with Shiraz University of Medical Sciences (Hafez, Namazi, and Zeinabieh). This study will be a single-blind trial. Due to the nature of the intervention, blinding of parents and the nursing staff administering the medication will not be feasible. physician and data analyst will be blinded.

Inclusion Criteria: Age ≤30 days, gestational age ≥35 weeks, indirect hyperbilirubinemia requiring phototherapy, parental informed consent Exclusion Criteria: Direct hyperbilirubinemia, major congenital anomalies, severe liver disease, previous UDCA exposure, hemodynamic instability, immediate need for exchange transfusion

Following informed parental consent, eligible neonates will be enrolled and randomly assigned to two groups. The intervention group will receive oral ursodeoxycholic acid (UDCA) at a dose of 10 mg/kg/dose twice daily in addition to intensive phototherapy, whereas the control group will receive intensive phototherapy alone.

Duration of phototherapy until discharge (hours)

The random allocation sequence will be generated using a permuted block randomization method with blocks of four, ensuring an equal distribution of participants between the intervention and control groups. All six possible block combinations (ABAB, BABA, AABB, BBAA, ABBA, and BAAB) will be used. A table of random numbers will be employed to determine the order of these blocks and create the final allocation list for 268 participants (67 blocks in total)

This study will be conducted as a single-blind trial. Due to the nature of the intervention, blinding of parents and the nursing staff administering the medication will not be feasible. However, the physician responsible for evaluating the outcomes will be blinded to group allocation to minimize assessment bias. In addition, the data analyst will also be blinded to the intervention groups during statistical analysis, using coded data to ensure objectivity.

Information regarding the primary outcome will be made available. Other data may be provided upon request in a de-identified format to protect patient confidentiality.

Immediately after publication of the article.

people working in academic institutions

Reputable academic institutions. The purpose and rationale for the data request will be reviewed at the time of the request, and access will be granted at the discretion of the investigators based on this assessment.

Requests must be submitted via email. Hamide Barzegar hamide.barzegar@gmail.com

The rationale and purpose of the request must be provided via email. If the request is approved, the available data will be provided within 48 hours.