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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension; Sarcoidosis
• Intervention / Treatment: Drug: Placebo; Drug: Placebo; Drug: Bosentan; Drug: Bosentan

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 Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States
      • Mount Sinai
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States
      • Cleveland Clinic
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States
      • University of Pittsburgh

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:

• 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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Bosentan for 16 weeks; Active drug	Drug: Bosentan; 62.5 mg bid for 4 weeks, then 125 mg bid; Other Names: Tracleer; Drug: Bosentan; drug given for 16 weeks; Other Names: tracleer
Placebo Comparator: Placebo; Placebo for 16 weeks	Drug: Placebo; placebo; Drug: Placebo; Placebo twice a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Improvement in six minute walk distance	16 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in pulmonary hemodynamics	16 weeks
Improvement in quality of life with therapy	48 weeks
Safety of treatment	48 weeks

Collaborators and Investigators

• Sponsor: University of Cincinnati
• Collaborators: Actelion
• Investigators: Principal Investigator: Robert P Baughman, MD, University of Cincinnati

Publications and helpful links

General Publications

• Baughman RP, Culver DA, Cordova FC, Padilla M, Gibson KF, Lower EE, Engel PJ. Bosentan for sarcoidosis-associated pulmonary hypertension: a double-blind placebo controlled randomized trial. Chest. 2014 Apr;145(4):810-817. doi: 10.1378/chest.13-1766.

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: December 26, 2007
• First Submitted That Met QC Criteria: December 26, 2007
• First Posted (Estimate): December 27, 2007

Study Record Updates

• Last Update Posted (Estimate): April 12, 2013
• Last Update Submitted That Met QC Criteria: April 10, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Sarcoidosis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Lung Diseases; Hypertension; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Sarcoidosis; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Endothelin Receptor Antagonists; Bosentan
• Other Study ID Numbers: BOSAPAH-1; 7-3-22-1