Bosentan for Treatment of Hepatopulmonary Syndrome in Patients With Liver Cirrhosis

Study Overview
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Brief Summary
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The most common observed cause of gas exchange abnormalities and hypoxemia in cirrhosis is the hepatopulmonary syndrome (HPS) with a reported prevalence of 20-47% in patients with hepatic impairment and cirrhosis. HPS is by far the most frequent respiratory complication of cirrhosis. It is a progressive disease leading to significantly increased mortality. Up to date, the only therapeutic option is liver transplantation. The study hypothesis is that administration of bosentan in patients with liver cirrhosis suffering from hepatopulmonary syndrome improves gas exchange. 18 patients with liver cirrhosis fulfilling criteria of HPS according to the ERS task force criteria will be included in this block randomized, double-blind, placebo controlled study (12 patients will be treated with bosentan, 6 with placebo). Patients will receive bosentan 62,5mg b.i.d. for 4 weeks and 125 mg b.i.d. for 8 weeks or placebo. The duration of the treatment phase of the study is 12 weeks. The primary endpoint is the alteration of gas exchange after 3 months of therapy. The expected duration of the study is 2 years.

Official Title
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Bosentan for Treatment of Hepatopulmonary Syndrome in Patients With Liver Cirrhosis - a Prospective Double Blind Randomized Controlled Clinical Study

Conditions
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Hepatopulmonary Syndrome, Liver Cirrhosis

Intervention / Treatment
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* Drug: bosentan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presence of HPS Age ≥ 18 years Exclusion Criteria: Intracardiac shunting Pregnancy Known hypersensitivity to bosentan Use of glyburide Use of cyclosporin A Elevation of aminotransferase level of > 3 times the upper limit of normal Use of rifampicin Females of childbearing potential without use of adequate contraception Systolic blood pressure < 85 mmHg Clinical relevant anemia HIV-infection

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>Patients will receive placebo tablets twice daily for 3 months. | Drug: Placebo<br>* pts. will receive placebo for 3 months<br>|
| Active Comparator: bosentan<br>pts. will receive bosentan for 3 months | Drug: bosentan<br>* pts. will receive bosentan for 3 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| alveolar-arterial oxygen gradient in mmHg |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| presence of HPS | assessment via contrast enhanced transthoracic echocardiography and pulmonary function testing | 3 months | 
| 6 minutes walking distance in m |  | 3 months | 
| WHO functional class |  | 3 months | 
| quality of life | we will us the CAT-questionaire for QoL assessment | 3 months | 
| aminotransferase level (ASAT, ALAT) | Assessment of the aminotransferase levels in U/L | 3 months | 
| exhanled nitric oxide in parts per billion |  | 3 months | 
| hepatic venous pressure gradient (HVPG) in mmHg | HVPG will be assessed after inclusion in the study and after 3 months | 3 months | 
| pulmonary hemodynamics | pulmonary hemodynamics will be assessed after inclusion and after 3 months | 3 months | 
| mean arterial blood pressue in mmHg |  | 3 months | 
| partial pressure of arterial oxygen in mmHg |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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patients