Bosentan for Treatment of Hepatopulmonary Syndrome in Patients With Liver Cirrhosis

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

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.

Study Overview

• Status: Terminated
• Conditions: Liver Cirrhosis; Hepatopulmonary Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: bosentan

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University Vienna, Dpt. of Internal Medicine 3, Div. of Gastroenterology and Hepatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; Patients will receive placebo tablets twice daily for 3 months.	Drug: Placebo; pts. will receive placebo for 3 months
Active Comparator: bosentan; pts. will receive bosentan for 3 months	Drug: bosentan; pts. will receive bosentan for 3 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Valentin H Fuhrmann, MD, Medical University Vienna

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: October 26, 2011
• First Submitted That Met QC Criteria: January 25, 2012
• First Posted (Estimate): January 26, 2012

Study Record Updates

• Last Update Posted (Estimate): September 28, 2016
• Last Update Submitted That Met QC Criteria: September 27, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: patients
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Disease; Liver Diseases; Fibrosis; Syndrome; Liver Cirrhosis; Hepatopulmonary Syndrome; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Endothelin Receptor Antagonists; Bosentan
• Other Study ID Numbers: 1-Fuhrmann