Effectiveness of oral methylprednisolone as an additional treatment for infants with cholestasis in Dr Soetomo General Academic Hospital, Surabaya, Indonesia

ISRCTN	ISRCTN45080388
DOI	https://doi.org/10.1186/ISRCTN45080388
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	0468/KEPK/VIII/2022
Sponsor	Airlangga University
Funder	Kementerian Pendidikan, Kebudayaan, Riset, dan Teknologi

Submission date: 22/10/2022
Registration date: 29/10/2022
Last edited: 09/08/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Digestive System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Cholestasis is an obstruction of bile flow which causes disruption of the secretion of various substances from the liver into the duodenum (small intestine), so that these materials are retained in the liver and cause damage. The diagnosis of cholestasis is based on clinical conditions and laboratory tests. Clinically, the baby looks yellow (jaundice) with a serum direct bilirubin level over 1.5 mg/dl and/or over 15% of the total bilirubin level. Oral corticosteroids have been used in clinical practice in infants with cholestasis and mostly give satisfactory results if given early before the baby is 2 months old. However, no randomized controlled trial (RCT) has been conducted to compare the improvement of cholestasis in infants receiving oral corticosteroids vs placebo (dummy drug). Until now there have been no publications on the use of corticosteroids as the main treatment of biliary atresia (bile duct blockage), although many experts believe that an immunological process (inflammatory and autoreactive) is the underlying cause. The aim of this study is to analyze the effect of giving oral methylprednisolone to infants with cholestasis on the improvement of jaundice, stool color, blood biochemical levels, and inflammatory markers.

Who can participate?
Patients aged 14 days to 3 months old with cholestasis

What does the study involve?
Participants are randomly allocated into two groups. The intervention group receive a combination of oral methylprednisolone (generic) and standard therapy for 14 days with dose 2 mg/kg/day in divided doses. The control group receive placebo and standard therapy for 14 days. Standard therapy given is urdafalk 10 mg/kg/time every 8 hours.

What are the possible benefits and risks of participating?
By participating in this study, parents get information about the condition of their child's disease because a complete examination is carried out and they will be followed up on a regular basis. Parents also get a souvenir.
There are several possible risks such as a chubby face (moon face), vomiting, diarrhea, and constipation. Drawing blood can cause risks such as pain and bruising at the needle puncture site. Even though all efforts have been made to minimize the risk in this study, there is always the possibility that undesirable things will occur, such as the child not feeling comfortable or other side effects of treatment, such as a moon face, vomiting, diarrhea, constipation, and disturbances in blood glucose levels that can occur from side effects of the treatment. Participants can withdraw from the study at any time.

Where is the study run from?
Dr Soetomo General Academic Hospital (Indonesia)

When is the study starting and how long is it expected to run for?
June 2022 to August 2023

Who is funding the study?
Kemdikbudristek (Indonesia)

Who is the main contact?
Bagus Setyoboedi, bagus.setyoboedi@fk.unair.ac.id

Contact information

Dr Bagus Setyoboedi
Principal investigator

Jl Prof Dr. Moestopo 6-8 Surabaya
Surabaya
60286
Indonesia

Phone	+62 (0)8123560043
Email	bagus.setyoboedi@fk.unair.ac.id

Study information

Primary study design	Interventional
Study design	Single interventional double-blinded randomized controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Effectiveness of oral methylprednisolone as adjuvant therapy on clinical improvement, biochemical markers, and inflammation in infants with cholestasis
Study objectives	There is an effect of oral methylprednisolone in infants with cholestasis on the improvement of jaundice, stool color, blood biochemical levels (bilirubin, aspartate aminotransferase [AST], alanine aminotransferase [ALT]), and inflammatory markers
Ethics approval(s)	Approved 15/08/2022, Ethical Committee of Dr Soetomo General Academic Hospital, Surabaya, Indonesia (Jl Prof Dr. Moestopo 6-8 Surabaya, East Java, Indonesia; +62 (0)31 5501164; kepk@rsudrsoetomo.jatimprov.go.id), ref: 0648/KEPK/VIII/2022
Health condition(s) or problem(s) studied	Cholestasis
Intervention	Subjects are randomised into two groups, namely: 1. Methylprednisolone (+)/intervention group: receive a combination of oral methylprednisolone (generic) and standard therapy for 14 days with dose 2 mg/kg/day in divided doses. After 14 days of subjects receiving methylprednisolone, the observation is completed and the patient is continued with services according to the protocol. 2. Methylprednisolone (-)/control group: receive placebo and standard therapy for 14 days. Standard therapy given is urdafalk 10 mg/kg/time every 8 hours.
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Metylprednisolone (generic)
Primary outcome measure(s)	1. Stool colour measured using stool colour card at baseline and 14 days 2. Level of AST, ALT and bilirubin measured using ELISA at baseline and 14 days 3. Level of marker inflammation (IFN-γ, IL1β, IL2, IL4, IL6, IL10, TGF-β, ANCA) measured using ELISA at baseline and 14 days
Key secondary outcome measure(s)	There are no secondary outcome measures
Completion date	01/08/2023

Eligibility

Participant type(s)	Patient
Age group	Mixed
Lower age limit	14 Days
Upper age limit	3 Months
Sex	All
Target sample size at registration	40
Total final enrolment	40
Key inclusion criteria	1. Suffered from cholestasis 2. Aged 14 days to 3 months old
Key exclusion criteria	1. Suffering from congenital abnormalities 2. Suffering from genetic disorders 3. Suffering from severe infection/sepsis 4. Hemodynamic condition is unstable 5. Parents refuse to participate in research
Date of first enrolment	13/10/2022
Date of final enrolment	15/07/2023

Locations

Countries of recruitment

Indonesia

Study participating centre

Airlangga University

Jl Prof Dr Moestopo 6-8 Surabaya
Surabaya
60286
Indonesia

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Other
IPD sharing plan	Raw data including the characteristics of participants and laboratory results will be shared 1 year after the study and for 2 years with a link that will be available in the journal.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		14/07/2024	09/08/2024	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

09/08/2024: Publication reference and total final enrolment added.
28/10/2022: Trial's existence confirmed by the Ethical Committee of Dr Soetomo General Academic Hospital.