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Pilot Study of Pentoxifylline for Hepatopulmonary Syndrome

This study has been terminated.
(Poor tolerability of drug and side effects)
Sponsor:
ClinicalTrials.gov Identifier:
NCT00593658
First Posted: January 15, 2008
Last Update Posted: March 9, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by:
University of Alabama at Birmingham
  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: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open Label Single Arm Pilot Study of Pentoxifylline in Advanced Hepatopulmonary Syndrome

Resource links provided by NLM:


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 ]

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

Enrollment: 9
Study Start Date: June 2004
Study Completion Date: October 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

Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

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
R03DK065958 ( U.S. NIH Grant/Contract )
First Submitted: January 3, 2008
First Posted: January 15, 2008
Last Update Posted: March 9, 2015
Last Verified: January 2008

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

Additional relevant MeSH terms:
Syndrome
Hepatopulmonary Syndrome
Disease
Pathologic Processes
Liver Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Pentoxifylline
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Radiation-Protective Agents
Protective Agents
Physiological Effects of Drugs
Vasodilator Agents
Free Radical Scavengers
Antioxidants