Combination Therapy in Pulmonary Arterial Hypertension

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00433329
• Date of registration: 07/02/2007
• Prospective Registration: Yes
• Primary sponsor: Actelion
• Public title: Combination Therapy in Pulmonary Arterial Hypertension COMPASS 3
• Scientific 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
• Date of first enrolment: March 2007
• Target sample size: 100
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00433329
• Study type: Interventional
• Phase: Phase 4

Countries of recruitment

United States

Key inclusion & exclusion 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.



Age minimum: 12 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Pulmonary Arterial Hypertension

Intervention(s)

Drug: Sildenafil

Drug: Bosentan

Primary Outcome(s)

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]

Secondary ID(s)

AC-052-419

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 17/05/2013
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00433329