Double Blind, Randomized Trial of Bosentan for Sarcoidosis Associated Pulmonary Hypertension

Phase 2

Completed

• Conditions: Pulmonary Arterial Hypertension; Sarcoidosis
• Interventions: Drug: Placebo; Drug: Bosentan

• Registration Number: NCT00581607
• Lead Sponsor: University of Cincinnati

Brief Summary

Patients with advanced sarcoidosis often develop pulmonary hypertension. Pulmonary hypertension is a condition where the right side of the heart has to push the blood though the lungs at a higher pressure than normal. Since this pressure is higher, it is harder for the heart to pump the blood through the lungs to the left side of the body. If the blood can not get through the lungs, it can not get pumped through the rest of the body. This leads to weakness and shortness of breath. This type of hypertension does not usually respond to regular blood pressure medicines. The purpose of this study is to determine if bosentan (Tracleer) will help sarcoidosis associated pulmonary hypertension.

Detailed Description

Patients will be randomized in 2:1 manner to receive either bosentan or placebo for 16 weeks. After 16 weeks, there will be an additional 32 weeks of an open label extension.

Study Timeline

• Study First Submitted: 2007-12-26
• Study First Submitted QC: 2007-12-26
• Study First Posted: 2007-12-27
• Study Start: 2008-04
• Primary Completion: 2012-10
• Study Completion: 2012-12
• Status Verified: 2013-04
• Last Update Submitted: 2013-04-10
• Last Update Posted: 2013-04-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 43

Inclusion Criteria

• Patients with known sarcoidosis 21.
• Age 18 or greater
• Patients with documented pulmonary hypertension with a PA mean > 25 mm Hg as measured by cardiac catheterization within six months of entry into the study. Pulmonary artery occluding pressure and or left ventricular end diastolic pressure must be less than 15 mm Hg.
• Patients with WHO class II or III
• Six minute walk distance of between 100 to 500 meters
• Patients on stable immunotherapy for their sarcoidosis, including prednisone, methotrexate, azathioprine, hydroxychloroquine, cyclophosphamide, thalidomide, and/or infliximab
• Patients able to provide written consent

Exclusion Criteria

• Patients on pulmonary vasodilator drugs (flolan, remodulin, bosentan, sildenafil) n the prior 28 days. Patients on stable dose of calcium channel blocker for more than 1 month prior to right heart catheterization can be continued on the calcium channel blocker.
• Patients with severe airway obstruction as defined by FEV1/FVC of less than 35%
• Patients with World Health Organization (WHO) class IV status.
• Patients who are pregnant or breast feeding
• Patients with significant left ventricular dysfunction with a left ventricular ejection fraction of less than 35%
• Cardiac index < 2.0 liters and/or right atrial pressure >15 mm Hg
• Significant liver dysfunction not due to sarcoidosis.
• Patients with severe other organ disease felt by investigators to impact on survival during the course of the study.
• Patients unable to perform the 6 minute walk study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo for 16 weeks
Bosentan for 16 weeks	Bosentan	Active drug

Primary Outcome Measures

Name	Time	Method
Improvement in six minute walk distance	16 weeks

Secondary Outcome Measures

Name	Time	Method
Change in pulmonary hemodynamics	16 weeks
Improvement in quality of life with therapy	48 weeks
Safety of treatment	48 weeks

Trial Locations

Locations (4)

Mount Sinai; 🇺🇸 New York, New York, United States

University of Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States