Clinical trial NCT01518595: Bosentan for Treatment of Hepatopulmonary Syndrome in Patients With Liver Cirrhosis
Official title: Bosentan for Treatment of Hepatopulmonary Syndrome in Patients With Liver Cirrhosis - a Prospective Double Blind Randomized Controlled Clinical Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hepatopulmonary Syndrome
Liver Cirrhosis
Keywords: patients
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2012-01-26
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: alveolar-arterial oxygen gradient in mmHg
timeFrame: 3 months
Secondary outcomes:
measure: presence of HPS
timeFrame: 3 months
measure: 6 minutes walking distance in m
timeFrame: 3 months
measure: WHO functional class
timeFrame: 3 months
measure: quality of life
timeFrame: 3 months
measure: aminotransferase level (ASAT, ALAT)
timeFrame: 3 months
measure: exhanled nitric oxide in parts per billion
timeFrame: 3 months
measure: hepatic venous pressure gradient (HVPG) in mmHg
timeFrame: 3 months
measure: pulmonary hemodynamics
timeFrame: 3 months
measure: mean arterial blood pressue in mmHg
timeFrame: 3 months
measure: partial pressure of arterial oxygen in mmHg
timeFrame: 3 months
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University Vienna, Dpt. of Internal Medicine 3, Div. of Gastroenterology and Hepatology
Study officials:
affiliation: Medical University Vienna
name: Valentin H Fuhrmann, MD
role: PRINCIPAL_INVESTIGATOR
References: