Pilot Study of Pentoxifylline for Hepatopulmonary Syndrome

March 6, 2015 updated by: University of Alabama at Birmingham

Open Label Single Arm Pilot Study of Pentoxifylline in Advanced Hepatopulmonary Syndrome

The Hepatopulmonary syndrome (HPS) results from intrapulmonary microvascular dilatation that impairs arterial oxygenation in the setting of cirrhosis or portal hypertension. As many as 10-20% of cirrhotics being evaluated for orthotopic liver transplantation (OLT) have advanced HPS and mortality is greater in those with HPS than in those without HPS. Currently, OLT is the only effective treatment, although post-operative mortality in HPS is increased relative to cirrhotic patients without HPS, with a one-year survival of between 68-80 %. Therefore, an effective medical therapy for advanced HPS could improve both pre-operative and post-operative mortality.

Recent work in experimental models of HPS has revealed that both nitric oxide synthase-derived nitric oxide and heme oxygenase-derived carbon monoxide cause intrapulmonary vasodilatation. These alterations appear to be driven in part by TNF-α modulation of pulmonary blood flow and intravascular monocyte accumulation. Pentoxifylline is a nonspecific phosphodiesterase inhibitor with inhibitory effects on TNF-α and has recently been shown to be beneficial in patients with severe alcoholic hepatitis where TNF-α overproduction contributes to liver injury. In experimental HPS, pentoxifylline administration also decreases the severity of oxygenation abnormalities. However, pentoxifylline therapy has been associated with dose limiting side effects in patients with liver disease and the tolerability of pentoxifylline in cirrhotic patients with advanced HPS is unknown. Therefore, this open label single arm clinical trial was designed to evaluate the efficacy and tolerability of 8 weeks of pentoxifylline in cirrhotic patients with advanced HPS being considered for OLT.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 1

Contacts and Locations

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

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham

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

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patient undergoing liver transplantation evaluation for cirrhosis
  • HPS (positive contrast echocardiography, hypoxemia, no other cause)
  • PaO2 < 65mmHg
  • ability and willingness to give informed consent

Exclusion Criteria:

  • Patients under the age of 19
  • active bacterial infections
  • known malignancy
  • intrinsic cardiopulmonary disease
  • known intolerance to pentoxifylline

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: single
Drug: pentoxifylline
pentoxifylline extended release 800mg PO TID for 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
change in arterial oxygenation (PaO2) and/or alveolar arterial oxygen gradient
Time Frame: 8 weeks
8 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
adverse events and safety of pentoxifylline therapy
Time Frame: 8 weeks
8 weeks

Collaborators and Investigators

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

Sponsor

University of Alabama at Birmingham

Investigators

  • Principal Investigator: Michael B Fallon, MD, University of Alabama at Birmingham

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

June 1, 2004

Primary Completion (Actual)

October 1, 2006

Study Completion (Actual)

October 1, 2006

Study Registration Dates

First Submitted

January 3, 2008

First Submitted That Met QC Criteria

January 3, 2008

First Posted (Estimate)

January 15, 2008

Study Record Updates

Last Update Posted (Estimate)

March 9, 2015

Last Update Submitted That Met QC Criteria

March 6, 2015

Last Verified

January 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • F030604005
  • R03DK065958 (U.S. NIH Grant/Contract)

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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