Hemodynamic effects of a single dose of sildenafil in symptomatic patients on bosentan treatment for pulmonary arterial hypertension A multicenter, open-label, non-comparative, prospective, phase II study - COMPASS 1

Active, not recruiting

Conditions: Patients suffering from pulmonary arterial hypertension PAH
MedDRA version: 6.1Level: PTClassification code 10037400

Registration Number: EUCTR2005-005066-37-IT

Lead Sponsor: Actelion Pharmaceuticals Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Not Recruiting

Sex: All

Target Recruitment: 44

Inclusion Criteria

1 Signed informed consent 2 Men or women 18 years of age 3 Symptomatic PAH WHO functional class II-III 4 PAH diagnosed by right heart catheter within 24 months before enrollment, showing a. mPAP 25 mmHg b. PCWP 15 mmHg 5 Documented non-responsiveness to vasoreactivity testing done within 24 months before enrollment but before start of bosentan therapy 6 Treated with bosentan 125 mg b.i.d. as monotherapy for PAH for at least 12 weeks before enrollment 7 Patient stable for at least 12 weeks before enrollment 8 Right heart catheterization for 2-3 hours medically acceptable 9 PVR at baseline 1 on the day of study performance 320 dyn.sec/cm5 10 Women of childbearing potential must have a negative pre-treatment urine pregnancy test and use a reliable method of contraception during study treatment and for at least 3 months after study treatment termination
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1 Other types of PAH than listed above 2 Epoprostenol treatment planned 3 Suspected pulmonary veno-occlusive disease based on pulmonary edema during a previous vasoreactivity test or on abnormal findings compatible with that diagnosis septal lines or pulmonary edema at high resolution computer tomography 4 Systolic blood pressure 85 mmHg 5 Body weight 40 kg 6 Hemoglobin 75 of the lower limit of the normal range 7 AST and/or ALT 3 times the upper limit of normal ranges 8 Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C 9 Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements 10 Conditions that prevent compliance with the protocol or adherence to therapy 11 Pregnancy or breast-feeding 12 Hypersensitivity to bosentan, sildenafil, or any of the excipients of their formulations 13 Use of an investigational drug within 3 months before enrollment 14 Treatment with PAH drugs, including ERA other than bosentan, PDE-5 inhibitors incl sildenafil, parenteral treatment e.g., epoprostenol , other prostanoids, NO, or L-arginine within 3 months before enrollment 15 Treatment with calcineurin inhibitors e.g., cyclosporine A, tacrolimus, everolimus, sirolimus , fluconazole, ketoconazole, miconazole, amiodarone, ritonavir, glibenclamide glyburide , alpha-blockers, nitrates, or calcium antagonists within 3 months before enrollment

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate that a single dose of sildenafil 25 mg reduces pulmonary vascular resistance PVR in symptomatic stable patients with pulmonary arterial hypertension PAH already treated with bosentan 125 mg b.i.d. for at least 12 weeks.;Secondary Objective: To assess the effect of a single dose of sildenafil 25 mg on 1 total pulmonary resistance TPR and on 2 N-terminal pro-B-type natriuretic peptide NT-pro-BNP in symptomatic stable patients with PAH already treated with bosentan 125 mg b.i.d. for at least 12 weeks.3 To explore whether previous treatment with bosentan 125 mg b.i.d. for at least 12 weeks promotes vasoreactivity in patients who had been non-responders in a previous acute vasoreactivity test.;Primary end point(s): PVR reduction from baseline 2 to 60 min after sildenafil administration expressed as percent change. This parameter is expected to be normally distributed with an SD of 20 . The reduction to be detected is 10 .

Secondary Outcome Measures