Pilot Study of Pentoxifylline for Hepatopulmonary Syndrome

Hepatopulmonary Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00593658
• Other study ID #: F030604005
• Secondary ID: RO3-DK65958
• Status: Terminated
• Phase: Phase 1
• First received: January 3, 2008
• Last updated: March 6, 2015
• Start date: June 2004
• Est. completion date: October 2006

Study information

• Verified date: January 2008
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: October 2006
• Est. primary completion date: October 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatopulmonary Syndrome
• Syndrome

Intervention

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

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
University of Alabama at Birmingham

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	change in arterial oxygenation (PaO2) and/or alveolar arterial oxygen gradient		8 weeks	No
Secondary	adverse events and safety of pentoxifylline therapy		8 weeks	Yes