Official Title: “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 Type: Interventional

Study Design: Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: October 2006

Intervention(s) in this Clinical Trial

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

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: single

Primary Measures

• change in arterial oxygenation (PaO2) and/or alveolar arterial oxygen gradient
  • Time Frame: 8 weeks
    Safety Issue?: No

Secondary Measures

• adverse events and safety of pentoxifylline therapy
  • Time Frame: 8 weeks
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 19 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Alabama at Birmingham

Overall Clinical Trial Officials and Contacts

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

Information obtained from ClinicalTrials.gov on September 04, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00593658

Study ID Number: F030604005

ClinicalTrials.gov Identifier: NCT00593658

Health Authority: United States: Food and Drug Administration