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Trial record 1 of 1 for:    NCT00433329
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Combination Therapy in Pulmonary Arterial Hypertension (COMPASS 3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00433329
Recruitment Status : Completed
First Posted : February 9, 2007
Results First Posted : May 17, 2013
Last Update Posted : June 5, 2013
Information provided by (Responsible Party):

Brief 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.

Condition or disease Intervention/treatment Phase
Pulmonary Arterial Hypertension Drug: Bosentan Drug: Sildenafil Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 100 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : March 2007
Actual Primary Completion Date : May 2010
Actual Study Completion Date : August 2010

Arm Intervention/treatment
Experimental: Bosentan
Oral bosentan 62.5 mg twice daily (BID) first 4 weeks, followed by 24 weeks of 125 mg BID if the 62.5 mg BID dose was well tolerated, with the addition of sildenafil 20 mg thrice daily (TID) in patients who do not reach the 6-MWT distance threshold at Week 16
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

Drug: Sildenafil
Oral sildenafil 20 mg TID in patients who do not reach the 6-MWT distance threshold at Week 16

Primary Outcome Measures :
  1. Number of Patients Reaching a 6-Minute Walk Test (6MWT) Distance ≥ 380 Meters [ Time Frame: at 16 weeks and at 28 weeks of a stepped approach to therapy ]
    The 6MWT is a non encouraged test, which measures the walking distance covered over a 6 minute period

Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00433329

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Sponsors and Collaborators

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Actelion Identifier: NCT00433329    
Other Study ID Numbers: AC-052-419
First Posted: February 9, 2007    Key Record Dates
Results First Posted: May 17, 2013
Last Update Posted: June 5, 2013
Last Verified: May 2013
Keywords provided by Actelion:
pulmonary arterial hypertension
combination therapy
Compass 3
Additional relevant MeSH terms:
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Familial Primary Pulmonary Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Sildenafil Citrate
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents
Antihypertensive Agents
Endothelin Receptor Antagonists