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Combination Therapy in Pulmonary Arterial Hypertension (COMPASS 3)
This study is currently recruiting participants.
Verified by Actelion, August 2009
First Received: February 7, 2007   Last Updated: August 4, 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

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

Resource links provided by NLM:


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

  Show 30 Study Locations
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: August 4, 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 September 02, 2009