Symptomatic Pulmonary Arterial Hypertension (WHO functional class II-III) of the following types: - Idiopathic - Familial - Associated with: Corrected congenital systemic-to-pulmonary shunts Drugs and toxins Patients are already on prescribed bosentan therapy for at least 12 weeks.
Conditions
Interventions
Trade Name: viagra
Product Name: sildenafil
Product Code: N/A
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Sildenafil ci
Sponsors
Actelion Pharmaceuticals Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Signed informed consent 2) Men or women >= 18 years of age 3) Symptomatic PAH (WHO functional class II-III) of the following types: - Idiopathic - Familial - Associated with: Corrected congenital systemic-to-pulmonary shunts Drugs and toxins 4) PAH diagnosed by right heart catheter within 24 months before enrollment, showing: - Mean pulmonary arterial pressure (mPAP) >= 25 mmHg - Pulmonary capillary wedge pressure (PCWP) = 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 bosentan treatment and for at least 3 months after bosentan 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) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 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 endothelin receptor antagonists 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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%. | — |
Countries
Belgium, Germany, Italy, United Kingdom
Outcome results
None listed