Ambrisentan for Treatment of Portopulmonary Hypertension

• ClinicalTrials.gov Identifier: NCT01733095
• Recruitment Status: Withdrawn
• First Posted: November 26, 2012
• Last Update Posted: June 17, 2016
• Sponsor: Medical University of Graz
• Information provided by (Responsible Party): Medical University of Graz

Tracking Information

• First Submitted Date: November 20, 2012
• First Posted Date: November 26, 2012
• Last Update Posted Date: June 17, 2016
• Study Start Date: July 2012
• Actual Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 20, 2012): pulmonary vascular resistance [ Time Frame: week 24 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 20, 2012)

• mean arterial pulmonary pressure [ Time Frame: week 24 ]
• hepatic venous pressure gradient [ Time Frame: week 24 ]
• exercise capacity [ Time Frame: week 24, 48 ]
• quality of life [ Time Frame: week 24, 48 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Ambrisentan for Treatment of Portopulmonary Hypertension
• Official Title: Ambrisentan for Treatment of Portopulmonary Hypertension (PoPH): a Pilot Study

Brief Summary

Portopulmonary hypertension denotes pulmonary hypertension complicating portal hypertension and is present in approximately 5% of cirrhotic patients. Treatment options include prostanoids, sildenafil, and the endothelin-receptor antagonists, bosentan and ambrisentan.

This study investigates the safety and efficacy of ambrisentan in portopulmonary hypertension.

• Detailed Description: Patients with clinically significant PoPH (resting mean pulmonary arterial pressure >25 mm Hg, pulmonary vascular resistance >400 dynes*s*cm-5) will be offered treatment with ambrisentan. Patients will be followed clinically and hemodynamically up to 12 months after start of treatment.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Portopulmonary Hypertension

Intervention

Drug: ambrisentan

Ambrisentan (Volibris 5 mg film-coated tablets, Glaxo Smith-Kline) will be started at 5 mg every other day and increased to 5 mg daily after 4 weeks if tolerated well.

Other Name: Volibris

Study Arms

Experimental: ambrisentan

In all patients with clinically significant PoPH, ambrisentan will be administered orally using a low ascending dose regime (see below). Duration of treatment will be 12 months.

Intervention: Drug: ambrisentan

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Withdrawn
• Actual Enrollment (submitted: June 16, 2016): 0
• Original Estimated Enrollment (submitted: November 20, 2012): 10
• Actual Study Completion Date: June 2016
• Actual Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Adult patients with portal hypertension, age >18 years
• Cirrhosis of any etiology; Child-Pugh class A and B
• Noncirrhotic portal hypertension (e.g. chronic portal vein thrombosis)
• Informed consent

Exclusion Criteria:

• Presence of other causes for pulmonary arterial hypertension
• History of pulmonary embolism or myocardial infarction within 6 months before study start
• Child-Pugh class C
• Presence of hepatocellular carcinoma
• Liver transplantation
• HIV infection
• Severe obstructive or restrictive pulmonary disease (predicted FEV1 or VC <65%, respectively)
• Severe dilated cardiomyopathy (EF <50%)
• Latent left-heart insufficiency
• Pregnancy and lactation
• Esophageal variceal hemorrhage within the last 6 months
• Refractory ascites
• Hepatorenal syndrome
• Persistent hepatic encephalopathy > grade 1
• Bilirubin >3.0 mg/dl
• AST and/or ALT >3x ULN
• Creatinine >2.0 mg/dl
• Known hypersensitivity to ambrisentan

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria

Administrative Information

• NCT Number: NCT01733095
• Other Study ID Numbers: PoPH-GRZ ambrisentan
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Medical University of Graz
• Study Sponsor: Medical University of Graz
• Collaborators: Not Provided

Investigators

• Principal Investigator: Rudolf E. Stauber, MD; Gastroenterology & Hepatology
• Study Director: Horst Olschewski, MD; Pulmonology

• PRS Account: Medical University of Graz
• Verification Date: June 2016