Hepatopulmonary Syndrome, Liver Cirrhosis
Conditions
Keywords
patients
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.
Interventions
DRUGbosentan
pts. will receive bosentan for 3 months
DRUGPlacebo
pts. will receive placebo for 3 months
Sponsors
Medical University of Vienna
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| alveolar-arterial oxygen gradient in mmHg | 3 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 6 minutes walking distance in m | 3 months | — |
| WHO functional class | 3 months | — |
| quality of life | 3 months | we will us the CAT-questionaire for QoL assessment |
| aminotransferase level (ASAT, ALAT) | 3 months | Assessment of the aminotransferase levels in U/L |
| presence of HPS | 3 months | assessment via contrast enhanced transthoracic echocardiography and pulmonary function testing |
| hepatic venous pressure gradient (HVPG) in mmHg | 3 months | HVPG will be assessed after inclusion in the study and after 3 months |
| pulmonary hemodynamics | 3 months | pulmonary hemodynamics will be assessed after inclusion and after 3 months |
| mean arterial blood pressue in mmHg | 3 months | — |
| partial pressure of arterial oxygen in mmHg | 3 months | — |
| exhanled nitric oxide in parts per billion | 3 months | — |
Countries
Austria
Outcome results
None listed