Combination Therapy in Pulmonary Arterial Hypertension (COMPASS 3)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Actelion
ClinicalTrials.gov Identifier:
NCT00433329
First received: February 7, 2007
Last updated: May 30, 2013
Last verified: May 2013
  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 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 Intervention Phase
Pulmonary Arterial Hypertension
Drug: Bosentan
Drug: Sildenafil
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Actelion:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    The 6MWT is a non encouraged test, which measures the walking distance covered over a 6 minute period


Enrollment: 100
Study Start Date: March 2007
Study Completion Date: August 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  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 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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00433329

  Show 26 Study Locations
Sponsors and Collaborators
Actelion
  More Information

No publications provided

Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT00433329     History of Changes
Other Study ID Numbers: AC-052-419
Study First Received: February 7, 2007
Results First Received: March 27, 2013
Last Updated: May 30, 2013
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Hypertension, Pulmonary
Hypertension
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases
Bosentan
Sildenafil
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents

ClinicalTrials.gov processed this record on July 31, 2014