Pentoxifylline Therapy in Biliary Atresia

This study is currently recruiting participants.
Verified January 2013 by Baylor College of Medicine
Sponsor:
Collaborator:
Texas Children's Hospital
Information provided by (Responsible Party):
Sanjiv Harpavat, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT01774487
First received: January 22, 2013
Last updated: January 23, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Biliary Atresia
Drug: Pentoxifylline
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Pentoxifylline in Newly-Diagnosed Biliary Atresia

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Change in serum conjugated bilirubin [ Time Frame: Baseline and after 90 days of therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in Weight [ Time Frame: Baseline and after 90 days of therapy ] [ Designated as safety issue: No ]
  • Change in serum markers [ Time Frame: Baseline and up to two years after therapy finishes ] [ Designated as safety issue: No ]
    The investigators will track the change in serum liver markers and platelets over the course of two years in patients receiving 90 days of PTX therapy.

  • Change in liver imaging [ Time Frame: Baseline and up to two years after therapy finishes ] [ Designated as safety issue: No ]
    The investigators will track liver ultrasound changes, including liver and spleen size.

  • Time to liver transplant [ Time Frame: Baseline and up to two years after therapy finishes ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: January 2013
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Trental

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.

  Eligibility

Ages Eligible for Study:   up to 180 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01774487

Contacts
Contact: Sanjiv Harpavat, MD PhD 832-824-2099 ext 2144 harpavat@bcm.edu
Contact: Ross Shepherd, MD 832-824-2099 ext 1223 Ross.Shepherd@bcm.edu

Locations
United States, Texas
Texas Children's Hospital and Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Sanjiv Harpavat, MD PhD    832-824-2099 ext 2144    harpavat@bcm.edu   
Contact: Ross Shepherd, MD    832-824-2099 ext 1223    Ross.Shepherd@bcm.edu   
Principal Investigator: Sanjiv Harpavat, MD PhD         
Principal Investigator: Ross Shepherd, MD         
Sub-Investigator: Mary Brandt, MD         
Sub-Investigator: Shelly Kim, PharmD         
Sub-Investigator: Charles Minard, PhD         
Sub-Investigator: Paula Hertel, MD         
Sub-Investigator: Milton Finegold, MD         
Sponsors and Collaborators
Baylor College of Medicine
Texas Children's Hospital
Investigators
Principal Investigator: Sanjiv Harpavat, MD PhD Baylor College of Medicine
Principal Investigator: Ross Shepherd, MD Baylor College of Medicine
  More Information

Publications:

Responsible Party: Sanjiv Harpavat, Assistant Professor, Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT01774487     History of Changes
Other Study ID Numbers: BCM/TCH-H-31387
Study First Received: January 22, 2013
Last Updated: January 23, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Baylor College of Medicine:
Biliary Atresia
Pentoxifylline
Trental
Serum bilirubin
Conjugated bilirubin
Liver transplantation
Fibrosis

Additional relevant MeSH terms:
Biliary Atresia
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Digestive System Abnormalities
Congenital Abnormalities
Pentoxifylline
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Radiation-Protective Agents
Protective Agents
Physiological Effects of Drugs
Vasodilator Agents
Cardiovascular Agents
Free Radical Scavengers
Antioxidants

ClinicalTrials.gov processed this record on April 17, 2014