too slow patient recruitment

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.

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