Pilot Study of Pentoxifylline for Hepatopulmonary Syndrome

The University of Alabama at Birmingham

Status and phase: Terminated; Phase 1

Conditions: Hepatopulmonary Syndrome

Treatments: Drug: pentoxifylline

Study type: Interventional

Funder types: Other

Identifiers

NCT00593658

F030604005

R03DK065958 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Enrollment: 9 patients

Sex: All

Ages: 19+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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9 participants in 1 patient group

single

Experimental group

Treatment:

Drug: pentoxifylline