Ambrisentan for Treatment of Portopulmonary Hypertension

Study Overview
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Brief Summary
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Portopulmonary hypertension denotes pulmonary hypertension complicating portal hypertension and is present in approximately 5% of cirrhotic patients. Treatment options include prostanoids, sildenafil, and the endothelin-receptor antagonists, bosentan and ambrisentan. This study investigates the safety and efficacy of ambrisentan in portopulmonary hypertension.

Detailed Description
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Patients with clinically significant PoPH (resting mean pulmonary arterial pressure >25 mm Hg, pulmonary vascular resistance >400 dynes*s*cm-5) will be offered treatment with ambrisentan. Patients will be followed clinically and hemodynamically up to 12 months after start of treatment.

Official Title
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Ambrisentan for Treatment of Portopulmonary Hypertension (PoPH): a Pilot Study

Conditions
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Portopulmonary Hypertension

Intervention / Treatment
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* Drug: ambrisentan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients with portal hypertension, age >18 years Cirrhosis of any etiology; Child-Pugh class A and B Noncirrhotic portal hypertension (e.g. chronic portal vein thrombosis) Informed consent Exclusion Criteria: Presence of other causes for pulmonary arterial hypertension History of pulmonary embolism or myocardial infarction within 6 months before study start Child-Pugh class C Presence of hepatocellular carcinoma Liver transplantation HIV infection Severe obstructive or restrictive pulmonary disease (predicted FEV1 or VC <65%, respectively) Severe dilated cardiomyopathy (EF <50%) Latent left-heart insufficiency Pregnancy and lactation Esophageal variceal hemorrhage within the last 6 months Refractory ascites Hepatorenal syndrome Persistent hepatic encephalopathy > grade 1 Bilirubin >3.0 mg/dl AST and/or ALT >3x ULN Creatinine >2.0 mg/dl Known hypersensitivity to ambrisentan

Ages Eligible for Study
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Minimum Age: 18 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: ambrisentan<br>In all patients with clinically significant PoPH, ambrisentan will be administered orally using a low ascending dose regime (see below). Duration of treatment will be 12 months. | Drug: ambrisentan<br>* Ambrisentan (Volibris 5 mg film-coated tablets, Glaxo Smith-Kline) will be started at 5 mg every other day and increased to 5 mg daily after 4 weeks if tolerated well.<br>* Other names: Volibris;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pulmonary vascular resistance |  | week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mean arterial pulmonary pressure |  | week 24 | 
| hepatic venous pressure gradient |  | week 24 | 
| exercise capacity |  | week 24, 48 | 
| quality of life |  | week 24, 48 |