Pentoxifylline Therapy in Biliary Atresia

January 9, 2024 updated by: Sanjiv Harpavat, Baylor College of Medicine

A Phase II Trial of Pentoxifylline in Newly-Diagnosed Biliary Atresia

The purpose of this study is to determine whether pentoxifylline reduces liver damage in infants with biliary atresia.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Biliary atresia (BA) is a devastating liver disease of infancy of unknown etiology, characterized by bile duct obstruction, live fibrosis, and cirrhosis. BA has no known medical treatments. The only proven treatment is a surgical portoenterostomy (the Kasai procedure, or KP) which can achieve bile drainage and improve outcomes in some cases. The KPs success is variable depending on several factors including age of the infant, experience of the surgeon, and extent of liver fibrosis at the time of KP.

In this study, the investigators conduct a phase II trial of a potential new medical therapy for BA: pentoxifylline (PTX). PTX is a methylxanthine derivative closely related to caffeine that has been used safely in infants with other diseases such as sepsis. In adults, PTX has been shown to have a number of properties beneficial to the liver, including preventing liver fibrosis, improving liver regeneration, and reducing cirrhosis-related complications.

The trial's objective is to determine whether PTX has sufficient biological activity against BA to warrant further study. PTX will be administered orally for 90 days as an adjunct to standard therapy (i.e. KP if appropriate). The primary outcome will measure the change in serum conjugated bilirubin levels after 90 days. Secondary outcomes include changes in body weight, serum markers, liver imaging, and time to liver transplant in infants with BA.

Study Type

Interventional

Enrollment (Actual)

17

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Sanjiv Harpavat, MD PhD
  • Phone Number: 2144 832-824-2099
  • Email: harpavat@bcm.edu

Study Contact Backup

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • Texas Children's Hospital and Baylor College of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 5 months (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 0-180 days old
  • Diagnosed with biliary atresia through liver biopsy and/or intra-operative cholangiogram
  • No previous Kasai portoenterostomy performed at another institution
  • Able to take medications orally
  • Legal guardian signs consent after understanding risks and investigational nature of study

Exclusion Criteria:

  • Infants greater than 180 days old
  • Infants receiving a Kasai portoenterostomy at another institution
  • Infants unable to take medications orally

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pentoxifylline

All newly-diagnosed biliary atresia patients fulfilling the study's inclusion criteria will receive oral pentoxifylline, 20 mg/kg/day divided in three doses for a total of 90 days.

The hospital pharmacy will create a 20 mg/ml oral pentoxifylline solution using 400 mg pentoxifylline tablets and established compounding recipes.
Drug: Pentoxifylline
20 mg/kg/day divided in 3 doses, given orally for 90 days
Other Names:
  • Trental

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Normal Serum Conjugated Bilirubin Levels 12 Weeks After Starting PTX (Pentoxifylline) Therapy
Time Frame: 12 weeks after starting therapy
The investigators will track the serum conjugated bilirubin (CB) levels over the course of therapy in patients receiving 90 days of PTX (this laboratory test is drawn as part of routine care). Normal CB is 0.0-0.3 mg/dL, with a higher number of patients meeting this indicating a better outcome.
12 weeks after starting therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Achieving Zero or Positive Weight Z-scores 12 Weeks After Starting PTX Therapy
Time Frame: 12 weeks after starting therapy
The investigators will track the weight of patients over the course of therapy in patients receiving 90 days of PTX (this is recorded as part of routine clinical care). The weight will then be compared to standards to calculate a z-score. Normal weight Z-score is greater than or equal to 0, with a higher number of patients meeting this indicating a better outcome.
12 weeks after starting therapy
Spleen Size at 2 Years of Age
Time Frame: 2 years of age
The investigators will measure spleen size by ultrasound at 2 years of age, in patients who had received PTX therapy earlier and still have their native liver. "Normal" spleen size range (10th-90th percentile) at this age is 6.4-8.6 cm, with a value exceeding this range indicating a worse outcome.
2 years of age
Time to Liver Transplant
Time Frame: Baseline and up to two years after therapy finishes
The investigators will track time to liver transplant. The shorter time to liver transplant indicates a worse outcome.
Baseline and up to two years after therapy finishes
Platelet Levels at 2 Years of Life
Time Frame: 2 years of age
The investigators will record platelet levels at age two years, in patients who had previously been treated with PTX therapy and still have their native liver. Scale 189-403*10^3 Platelets/μL, with a lower level indicating a worse outcome.
2 years of age
Alanine Amino Transferase (ALT) Levels at 2 Years of Life
Time Frame: 2 years of age
The investigators will record the ALT levels at age two years, in patients who had previously been treated with PTX therapy and still have their native liver. Range of normal values: 14-45 U/L, with a higher level indicating a worse outcome.
2 years of age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Baylor College of Medicine

Investigators

  • Principal Investigator: Sanjiv Harpavat, MD PhD, Baylor College of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 4, 2013

Primary Completion (Actual)

February 7, 2018

Study Completion (Actual)

February 20, 2023

Study Registration Dates

First Submitted

January 22, 2013

First Submitted That Met QC Criteria

January 22, 2013

First Posted (Estimated)

January 24, 2013

Study Record Updates

Last Update Posted (Estimated)

January 11, 2024

Last Update Submitted That Met QC Criteria

January 9, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-31387

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The data for subjects will be shared in aggregate.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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