Bosentan for Treatment of Hepatopulmonary Syndrome in Patients With Liver Cirrhosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01518595
Recruitment Status : Terminated (too slow patient recruitment)
First Posted : January 26, 2012
Last Update Posted : September 28, 2016
Information provided by (Responsible Party):
Valentin Fuhrmann, 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.

Condition or disease Intervention/treatment Phase
Hepatopulmonary Syndrome Liver Cirrhosis Drug: bosentan Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Bosentan for Treatment of Hepatopulmonary Syndrome in Patients With Liver Cirrhosis - a Prospective Double Blind Randomized Controlled Clinical Study
Study Start Date : October 2011
Actual Primary Completion Date : April 2014

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

Primary Outcome Measures :
  1. alveolar-arterial oxygen gradient in mmHg [ Time Frame: 3 months ]

Secondary Outcome Measures :
  1. presence of HPS [ Time Frame: 3 months ]
    assessment via contrast enhanced transthoracic echocardiography and pulmonary function testing

  2. 6 minutes walking distance in m [ Time Frame: 3 months ]
  3. WHO functional class [ Time Frame: 3 months ]
  4. quality of life [ Time Frame: 3 months ]
    we will us the CAT-questionaire for QoL assessment

  5. aminotransferase level (ASAT, ALAT) [ Time Frame: 3 months ]
    Assessment of the aminotransferase levels in U/L

  6. exhanled nitric oxide in parts per billion [ Time Frame: 3 months ]
  7. hepatic venous pressure gradient (HVPG) in mmHg [ Time Frame: 3 months ]
    HVPG will be assessed after inclusion in the study and after 3 months

  8. pulmonary hemodynamics [ Time Frame: 3 months ]
    pulmonary hemodynamics will be assessed after inclusion and after 3 months

  9. mean arterial blood pressue in mmHg [ Time Frame: 3 months ]
  10. partial pressure of arterial oxygen in mmHg [ Time Frame: 3 months ]

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01518595

Medical University Vienna, Dpt. of Internal Medicine 3, Div. of Gastroenterology and Hepatology
Vienna, Austria, 1090
Sponsors and Collaborators
Medical University of Vienna
Principal Investigator: Valentin H Fuhrmann, MD Medical University Vienna

Responsible Party: Valentin Fuhrmann, MD, Associate Professor of Medicine, Medical University of Vienna Identifier: NCT01518595     History of Changes
Other Study ID Numbers: 1-Fuhrmann
First Posted: January 26, 2012    Key Record Dates
Last Update Posted: September 28, 2016
Last Verified: September 2016

Keywords provided by Valentin Fuhrmann, Medical University of Vienna:

Additional relevant MeSH terms:
Liver Cirrhosis
Hepatopulmonary Syndrome
Pathologic Processes
Liver Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Antihypertensive Agents
Endothelin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action