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Pilot Study of Pentoxifylline for Hepatopulmonary Syndrome

This study has been terminated.
(Poor tolerability of drug and side effects)
Sponsor:
Information provided by:
University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT00593658
First received: January 3, 2008
Last updated: NA
Last verified: January 2008
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Hepatopulmonary Syndrome
 Drug: pentoxifylline
 Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open Label Single Arm Pilot Study of Pentoxifylline in Advanced Hepatopulmonary Syndrome

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • change in arterial oxygenation (PaO2) and/or alveolar arterial oxygen gradient [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • adverse events and safety of pentoxifylline therapy [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 9
Study Start Date: June 2004
Study Completion Date: September 2006
Primary Completion Date: October 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: single Drug: pentoxifylline
pentoxifylline extended release 800mg PO TID for 8 weeks

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00593658

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
Principal Investigator: Michael B Fallon, MD University of Alabama at Birmingham
  More Information

No publications provided by University of Alabama at Birmingham

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Michael B. Fallon, MD, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT00593658     History of Changes
Other Study ID Numbers: F030604005, RO3-DK65958
Study First Received: January 3, 2008
Last Updated: January 3, 2008
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Alabama at Birmingham:
hypoxemia
liver transplantation evaluation
cirrhosis

Additional relevant MeSH terms:
Hepatopulmonary Syndrome
Liver Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
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 May 21, 2013