Pilot Study of Pentoxifylline for Hepatopulmonary Syndrome

Study Overview
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Brief Summary
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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.

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

Conditions
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Hepatopulmonary Syndrome

Intervention / Treatment
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* Drug: pentoxifylline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: single<br> | Drug: pentoxifylline<br>* pentoxifylline extended release 800mg PO TID for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse events and safety of pentoxifylline therapy |  | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypoxemia, liver transplantation evaluation, cirrhosis