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Combination Therapy in Pulmonary Arterial Hypertension (COMPASS 3)
This study is currently recruiting participants.
Verified by Actelion, January 2009
First Received: February 7, 2007   Last Updated: January 29, 2009   History of Changes
Sponsored by: Actelion
Information provided by: Actelion
ClinicalTrials.gov Identifier: NCT00433329
  Purpose

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 PAH to achieve a 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.


Condition Intervention Phase
Pulmonary Arterial Hypertension
Drug: bosentan
Drug: bosentan and sildenafil combination
Phase IV

Genetics Home Reference related topics: pulmonary arterial hypertension
MedlinePlus related topics: High Blood Pressure
Drug Information available for: Sildenafil Bosentan Sildenafil citrate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study
Official Title: COMPASS 3: An Open-Label, Multi-Center Study Employing a Targeted 6-MWT Distance Threshold Approach to Guide Bosentan-Based Therapy and to Assess the Utility of MRI on Cardiac Remodeling

Further study details as provided by Actelion:

Primary Outcome Measures:
  • Proportion of patients reaching a 6-Minute Walk Test distance = 380 meters [ Time Frame: after 16 weeks and after 28 weeks of a stepped approach to therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The change for MRI-derived parameters [ Time Frame: From Baseline to Week 16 and Week 28 ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: March 2007
Estimated Study Completion Date: June 2009
Estimated Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
A: Active Comparator
Bosentan monotherapy
Drug: bosentan
Oral bosentan 62.5 mg BID for 4 weeks followed by 24 weeks of 125 mg BID
B: Active Comparator
bosentan and sildenafil combination therapy
Drug: bosentan and sildenafil combination
Oral bosentan 62.5 mg BID for 4 weeks followed by 24 weeks of 125 mg BID with the addition of sildenafil 20 mg TID in patients who do not reach the 6-MWT distance threshold at Week 16

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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., ERAs, PDE-5 inhibitors or prostacyclins) with a 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 ≥ 200 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 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.m2).
  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 (AST and/or ALT) > 1.5 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 unable to complete a MRI scan (e.g., claustrophobia).
  23. Patients with permanent cardiac pacemakers, AICD's, neurostimulators, hearing aides, and other implanted metallic devices that are contraindicated during a MRI study.
  24. Patients with conditions that would interfere with proper cardiac gating during MRI, such as atrial fibrillation or multiple PVCs/PACs.
  25. Patients with conditions that prevent compliance with the protocol or the ability to adhere to therapy.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00433329

  Hide Study Locations
Locations
United States, Alabama
University of Alabama Hospital at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Pamela Rhodes, RN     205-934-8767     prhodes@cardmail.dom.uab.edu    
Principal Investigator: Barry Rayburn, MD            
University of South Alabama Recruiting
Mobile, Alabama, United States, 36617
Contact: Majid Mughal, MD     251-471-7029     mmughal@usouthal.edu    
Principal Investigator: Majid Mughal, MD            
United States, California
Cedars Sinai Medical Center Withdrawn
Los Angeles, California, United States, 90048
UCLA - David Geffen School of Medicine Recruiting
Los Angeles, California, United States, 90095
Contact: David Ross, MD     310-206-8328     dross@mednet.ucla.edu    
Principal Investigator: David Ross, MD            
United States, Delaware
Lung Health and Sleep Enhancement Center, LLC Recruiting
Newark, Delaware, United States, 19713
Contact: Julie Adams     302-368-5515 ext Option 9     jadams@pulmonarydoctors.com    
Principal Investigator: Gerald M. O'Brien, MD            
United States, Florida
Morton Plant Hospital (Bay Area Chest Physicians, P.A.) Recruiting
Clearwater, Florida, United States, 33756
Contact: Devendra Amin, MD     727-443-0611     alveoli.dna@verizon.net    
Principal Investigator: Devendra Amin, MD            
University of Miami School of Medicine Recruiting
Miami, Florida, United States, 33136
Contact: Debra Fertel, MD     305-585-6487     dfertel@med.miami.edu    
Principal Investigator: Debra Fertel, MD            
Sarasota Memorial Hospital-Clinical Research Center Withdrawn
Sarasota, Florida, United States, 34239
Cleveland Clinic Florida Recruiting
Weston, Florida, United States, 33331
Contact: Franck Rahagi, MD     954-659-5450     rahaghf@ccf.org    
Principal Investigator: Franck Rahagi, MD            
Mayo Clinic Jacksonville Recruiting
Jacksonville, Florida, United States, 32258
Contact: Pam Long     904-953-7719     long.pamela@mayo.edu    
Principal Investigator: Jesus Diaz, MD            
United States, Georgia
Emory University Hospital Recruiting
Atlanta, Georgia, United States, 30322
Contact: Micah Fisher, MD     404-727-9651     Micah.Fisher@emoryhealthcare.org    
Principal Investigator: Micah Fisher, MD            
Atlanta Institute for Medical Research, Inc. Recruiting
Decatur, Georgia, United States, 30030
Contact: Jeffrey E Michaelson, MD     404-966-3775     michaelson@bellsouth.net    
Principal Investigator: Jeffrey E Michaelson, MD            
United States, Kentucky
Kentukiana Pulmonary Associates Recruiting
Louisville, Kentucky, United States, 40202
Contact: John McConnell, MD     502-587-8000        
Principal Investigator: John McConnell, MD            
United States, Maryland
University of Maryland School of Medicine Recruiting
Baltimore, Maryland, United States, 21201
Contact: Myung Park, MD     410-328-7260     mpark@medicine.umaryland.edu    
Principal Investigator: Myung Park, MD            
United States, Massachusetts
Boston Children's Hospital-BACH Cardiology Recruiting
Boston, Massachusetts, United States, 02115
Contact: Elizabeth Rodriguez     617-355-0646     elizabeth.rodriguez-huertas@cardio.CHBOSTON.org    
Principal Investigator: Michael Singh, MD            
United States, Minnesota
Mayo Clinic - Pulmonary Hypertension Clinic Withdrawn
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Murali Chakinala, MD     314-454-8766     mchakina@im.wustl.edu    
Principal Investigator: Murali Chakinala, MD            
United States, New York
Columbia University Medical Center Withdrawn
New York, New York, United States, 10032
Buffalo General Hospital / Kaleida Health Recruiting
Buffalo, New York, United States, 14203
Contact: William J. Gibbons, MD     716-859-2271     wgibbons@kaleidahealth.org    
Principal Investigator: William J. Gibbons, MD            
United States, Ohio
Ohio State University Medical Center-Davis Heart and Lung Institute Recruiting
Columbus, Ohio, United States, 43210
Contact: Pranav Ravi     614-688-5506     pranav.ravi@oscumc.edu    
Principal Investigator: Curt Daniels, MD            
The Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: Richard Krasuski, MD     216-445-7430     krasusr@ccf.org    
Contact: Joseph Parambil, MD     216-445-6024        
Principal Investigator: Richard Krasuski, MD            
Principal Investigator: Joseph Parambil, MD            
United States, Oklahoma
INTEGRIS Baptist Medical Center Recruiting
Oklahoma City, Oklahoma, United States, 73112
Contact: Remzi Bag, MD     405-951-2548     remzi.bag@integris-health.com    
Principal Investigator: Remzi Bag, MD            
United States, Oregon
The Oregon Clinic Recruiting
Portland, Oregon, United States, 97220
Contact: Rhett Cummings, MD     503-963-3030     rcummings@orclinic.com    
Principal Investigator: Rhett Cummings, MD            
United States, Pennsylvania
Allegheny General Hospital Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Carrie Meligary     412-359-3285     cmelegar@wpahs.org    
Principal Investigator: Srinivas Murali, MD            
University of Pittsburgh Medical Center - Presbyterian Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Yvette Mallory     412-692-2769     malloryy@upmc.edu    
Principal Investigator: Marc Simon, MD            
United States, Texas
Baylor College of Medicine and the Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Aadani Frost, MD     713-798-2400     frost@bcm.tmc.edu    
Principal Investigator: Aadani Frost, MD            
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Elizabaeth Owens     214-645-6489     Elizabeth.Owens@UTSouthwestern.edu    
Principal Investigator: Fernando Torres, MD            
United States, Utah
Central Utah Clinic, PC Recruiting
Provo, Utah, United States, 84604
Contact: Denise Roberts, RN, CRC     801-354-8268     droberts@centralutahclinic.com    
Contact: Rachel Hill         rhill@centralutahclinic.com    
Principal Investigator: Rodney S. Badger, MD            
United States, Virginia
Sentara Norfolk General Hospital Recruiting
Norfolk, Virginia, United States, 23507
Contact: Michael Eggert, MD     757-466-5949     msbe@aol.com    
Principal Investigator: Michael Eggert, MD            
United States, Wisconsin
Medical College of Wisconsin-Frodtert Memorial Lutheran Hospital Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Gary Kung     414-456-7046     gkung@mcw.edu    
Principal Investigator: Francisco Soto, MD            
Sponsors and Collaborators
Actelion
  More Information

No publications provided

Responsible Party: Actelion ( Lee Golden, MD )
Study ID Numbers: AC-052-419
Study First Received: February 7, 2007
Last Updated: January 29, 2009
ClinicalTrials.gov Identifier: NCT00433329     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by Actelion:
pulmonary arterial hypertension
bosentan
sildenafil
combination therapy
Compass 3

Study placed in the following topic categories:
Vasodilator Agents
Phosphodiesterase Inhibitors
Respiratory Tract Diseases
Hypertension, Pulmonary
Lung Diseases
Idiopathic Pulmonary Hypertension
Vascular Diseases
Sildenafil
Cardiovascular Agents
Antihypertensive Agents
Bosentan
Hypertension

Additional relevant MeSH terms:
Vasodilator Agents
Molecular Mechanisms of Pharmacological Action
Vascular Diseases
Enzyme Inhibitors
Sildenafil
Cardiovascular Agents
Antihypertensive Agents
Bosentan
Pharmacologic Actions
Phosphodiesterase Inhibitors
Respiratory Tract Diseases
Hypertension, Pulmonary
Lung Diseases
Therapeutic Uses
Cardiovascular Diseases
Hypertension

ClinicalTrials.gov processed this record on May 11, 2009