Clinical trial NCT00593658: Pilot Study of Pentoxifylline for Hepatopulmonary Syndrome
Official title: Open Label Single Arm Pilot Study of Pentoxifylline in Advanced Hepatopulmonary Syndrome
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Hepatopulmonary Syndrome
Keywords: hypoxemia
liver transplantation evaluation
cirrhosis
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
First posted: 2008-01-15
Enrollment: 9
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility 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

Primary outcomes:
measure: change in arterial oxygenation (PaO2) and/or alveolar arterial oxygen gradient
timeFrame: 8 weeks
Secondary outcomes:
measure: adverse events and safety of pentoxifylline therapy
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Michael B Fallon, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tanikella R, Philips GM, Faulk DK, Kawut SM, Fallon MB. Pilot study of pentoxifylline in hepatopulmonary syndrome. Liver Transpl. 2008 Aug;14(8):1199-203. doi: 10.1002/lt.21482.