Pilot Study of Pentoxifylline for Hepatopulmonary Syndrome
Information source: University of Alabama at Birmingham
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hepatopulmonary Syndrome
Intervention: pentoxifylline (Drug)
Phase: Phase 1
Status: Terminated
Sponsored by: University of Alabama at Birmingham Official(s) and/or principal investigator(s):
Michael B Fallon, MD, Principal Investigator, Affiliation: University of Alabama at Birmingham
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.
Clinical Details
Official title: Open Label Single Arm Pilot Study of Pentoxifylline in Advanced Hepatopulmonary Syndrome
Study design: Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Primary outcome: change in arterial oxygenation (PaO2) and/or alveolar arterial oxygen gradient
Secondary outcome: adverse events and safety of pentoxifylline therapy
Eligibility
Minimum age: 19 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
University of Alabama at Birmingham, Birmingham, Alabama 35294, United States
Additional Information
Starting date: June 2004
Ending date: September 2006
Last updated: January 3, 2008
|
