Bosentan for Treatment of Hepatopulmonary Syndrome in Patients With Liver Cirrhosis

Phase 2

Terminated

• Conditions: Liver Cirrhosis; Hepatopulmonary Syndrome
• Interventions: Drug: Placebo; Drug: bosentan

• Registration Number: NCT01518595
• Lead Sponsor: Medical University of Vienna

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-10
• Study First Submitted: 2011-10-26
• Study First Submitted QC: 2012-01-25
• Study First Posted: 2012-01-26
• Primary Completion: 2014-04
• Status Verified: 2016-09
• Last Update Submitted: 2016-09-27
• Last Update Posted: 2016-09-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 6

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	Placebo	Patients will receive placebo tablets twice daily for 3 months.
bosentan	bosentan	pts. will receive bosentan for 3 months

Primary Outcome Measures

Name	Time	Method
alveolar-arterial oxygen gradient in mmHg	3 months

Secondary Outcome Measures

Name	Time	Method
presence of HPS	3 months	assessment via contrast enhanced transthoracic echocardiography and pulmonary function testing
6 minutes walking distance in m	3 months
aminotransferase level (ASAT, ALAT)	3 months	Assessment of the aminotransferase levels in U/L
WHO functional class	3 months
exhanled nitric oxide in parts per billion	3 months
quality of life	3 months	we will us the CAT-questionaire for QoL assessment
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

Trial Locations

Locations (1)

Medical University Vienna, Dpt. of Internal Medicine 3, Div. of Gastroenterology and Hepatology; 🇦🇹 Vienna, Austria