Combination Therapy in Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension Clinical Trial

— COMPASS 3  

Official title:

COMPASS 3: An Open-label, Multi-Center Study Employing a Targeted 6-Minute Walk Test (6-MWT) Distance Threshold Approach to Guide Bosentan-Based Therapy and to Assess the Utility of Magnetic Resonance Imaging (MRI) on Cardiac Remodeling

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00433329
• Other study ID #: AC-052-419
• Status: Completed
• Phase: Phase 4
• First received: February 7, 2007
• Last updated: May 30, 2013
• Start date: March 2007
• Est. completion date: August 2010

Study information

• Verified date: May 2013
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

An open label, non-comparative study design is appropriate for this Phase 4 study designed to assess whether a core therapy of bosentan, either as monotherapy or with the addition of sildenafil, enables patients with pulmonary arterial hypertension (PAH) to achieve a 6-minute walk distance (6 MWD) of ≥380 meters after 28 weeks of therapy This design is also appropriate to pioneer the utility of cardiac MRI in assessing improved functional capacity in PAH and exploring its correlation with other parameters.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: August 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

1. Signed informed consent prior to initiation of any study-mandated procedures.

2. Males or females = 12 years of age (females of child-bearing potential must have been surgically sterilized or use a reliable method of contraception).

3. Symptomatic patients with the following types of PAH belonging to World Health Organization (WHO) Pulmonary Hypertension Classification Group I:

• Idiopathic (IPAH)

• Familial (FPAH)

• Associated with PAH (APAH):

• Collagen vascular disease

• Drugs and toxins

4. Patients naïve to treatment with advanced PAH therapies (i.e., endothelin receptor antagonists (ERAs), phosphodiesterase-5 (PDE-5) inhibitors or prostacyclins) with a right heart catheterization (RHC) showing all of the following:

• Mean pulmonary arterial pressure (mPAP) = 25 mm Hg

• Pulmonary capillary wedge pressure (PCWP) = 15 mm Hg or left ventricular end diastolic pressure (LVEDP) = 15 mm Hg when PCWP is not accurately obtained

• Pulmonary vascular resistance = 3 Wood units

5. 6-MWT distance = 150 meters and < 360 meters.

Exclusion Criteria:

1. Patients with Pulmonary Hypertension (PH) belonging to WHO Classification Group II-V.

2. Patients with PAH (WHO PH Classification Group I) other than that listed in the Inclusion Criteria.

3. Pregnant and/or nursing.

4. Women of childbearing potential not using a reliable method of contraception.

5. Patients with known human immunodeficiency virus (HIV) infection.

6. Patients with significant vasoreactivity during right heart catheterization (i.e., a fall in mPAP to < 40 mm Hg with a decrease of = 10 mm Hg and with a normal cardiac index = 2.5 l/min.m^2).

7. Patients with restrictive lung disease (i.e., total lung capacity (TLC) < 60% of normal predicted value).

8. Patients with obstructive lung disease (i.e., forced expiratory volume/ forced vital capacity (FEV1/FVC) < 0.5).

9. Patients with impaired left ventricular function (LVEF <50%) or diastolic dysfunction.

10. Patients with portal hypertension, cirrhosis, moderate to severe liver impairment (Child-Pugh Class B or C), or liver enzymes (Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)) > 3.0 times the upper limit of normal range.

11. Treatment with glibenclamide (glyburide) and calcineurin inhibitors (cyclosporine A, tacrolimus) sirolimus, everolimus up to 1 week prior to Baseline (Day 1).

12. Patients currently receiving or predicted to require treatment, during the course of the study, with nitrates, protease inhibitors, or alpha-blockers.

13. Patients with a hemoglobin concentration < 75 % of the lower limit of the normal range or < 8.5 g/dL.

14. Patients currently receiving or predicted to require treatment with a prostanoid during the course of the study.

15. Patients with systolic blood pressure < 85 mm Hg.

16. Patients with body weight < 40 kg.

17. Patients who have received any investigational product within 90 days prior to Baseline.

18. Patients who previously received any advanced therapy for PAH (e.g., ERAs, PDE-5 inhibitors or prostacyclins).

19. Patients with hypersensitivity to sildenafil or any excipients of its formulation.

20. Patients with any contraindication to sildenafil treatment (i.e., nitrates).

21. Patients with any recent medical condition limiting the ability to comply with the study requirements (i.e., stroke, myocardial infarction).

22. Patients with unstable PAH whose disease state would prohibit the completion of study procedures, in the opinion of the investigator.

23. Patients unable to complete a MRI scan (e.g., claustrophobia).

24. Patients with permanent cardiac pacemakers, automatic internal cardioverter defibrillators (AICD's), neurostimulators, hearing aides, and other implanted metallic devices that are contraindicated during a MRI study.

25. Patients with conditions that would interfere with proper cardiac gating during MRI, such as atrial fibrillation or multiple premature ventricular contractions (PVCs)/premature atrial contractions (PACs).

26. Patients with conditions that prevent compliance with the protocol or the ability to adhere to therapy.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Bosentan
Oral bosentan 62.5 mg BID first 4 weeks followed by 24 weeks of 125 mg BID if the 62.5 mg BID dose was well tolerated
• Sildenafil
Oral sildenafil 20 mg TID in patients who do not reach the 6-MWT distance threshold at Week 16

Locations

Country	Name	City	State
United States	Emory University Hospital	Atlanta	Georgia
United States	University of Maryland School of Medicine	Baltimore	Maryland
United States	University of Alabama Hospital at Birmingham	Birmingham	Alabama
United States	Boston Children's Hospital-BACH Cardiology	Boston	Massachusetts
United States	Buffalo General Hospital / Kaleida Health	Buffalo	New York
United States	Morton Plant Hospital (Bay Area Chest Physicians, P.A.)	Clearwater	Florida
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	Ohio State University Medical Center-Davis Heart and Lung Institute	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Atlanta Institute for Medical Research, Inc.	Decatur	Georgia
United States	Baylor College of Medicine and the Methodist Hospital	Houston	Texas
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	UCLA - David Geffen School of Medicine	Los Angeles	California
United States	Kentukiana Pulmonary Associates	Louisville	Kentucky
United States	University of Miami School of Medicine	Miami	Florida
United States	Medical College of Wisconsin-Frodtert Memorial Lutheran Hospital	Milwaukee	Wisconsin
United States	University of South Alabama	Mobile	Alabama
United States	Lung Health and Sleep Enhancement Center, LLC	Newark	Delaware
United States	Sentara Norfolk General Hospital	Norfolk	Virginia
United States	INTEGRIS Baptist Medical Center	Oklahoma City	Oklahoma
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Medical Center - Presbyterian	Pittsburgh	Pennsylvania
United States	The Oregon Clinic	Portland	Oregon
United States	Central Utah Clinic, PC	Provo	Utah
United States	Washington University School of Medicine	St. Louis	Missouri
United States	Cleveland Clinic Florida	Weston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients Reaching a 6-Minute Walk Test (6MWT) Distance = 380 Meters	The 6MWT is a non encouraged test, which measures the walking distance covered over a 6 minute period	at 16 weeks and at 28 weeks of a stepped approach to therapy	No