A MULTINATIONAL, MULTICENTRE, RANDOMIZED, PARALLEL GROUP, DOUBLE-BLIND STUDY TO ASSESS THE EFFICACY AND SAFETY OF 1 MG, 5 MG AND 20 MG TID OF ORAL SILDENAFIL IN THE TREATMENT OF SUBJECTS AGED 18 YEARS AND OVER WITH PULMONARY ARTERIAL HYPERTENSION (PAH) - ND
- Conditions
- Pulmonary arterial hypertension (PAH).MedDRA version: 9.1Level: LLTClassification code 10037400Term: Pulmonary hypertension
- Registration Number
- EUCTR2006-006748-76-IT
- Lead Sponsor
- PFIZER
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 284
1. Subjects aged 18 and over with any of the following conditions: Idiopathic Primary Pulmonary Arterial Hypertension (IPAH) PAH secondary to connective tissue disease PAH with surgical repair (at least 5 years previously) of atrial septal defect (ASD), ventricular septal defect (VSD), patent ductus arteriosus (PDA) and aorto-pulmonary window 2. Subjects with a mean pulmonary artery pressure of >/=25 mmHg and a pulmonary artery wedge pressure of /=100 m and 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
1. PAH secondary to any aetiology including congenital heart disease other than those specified in the inclusion criteria. 2. Subjects with significant (i.e.> 2+) valvular disease other than tricuspid regurgitation or pulmonary regurgitation. Subjects with previous surgical replacement of a valve may be eligible for entry into the study after consultation with a Pfizer study clinician provided the following conditions are satisfied: That there was no evidence of PAH secondary to valvular disease prior to surgery The prosthetic valve is functioning normally on echocardiography The valve replacement occurred at least one year prior to screening. 3. Subjects who have undergone atrial septostomy within 6 months prior to randomization (subjects who are required to undergo this procedure during the study should be withdrawn). 4. Subjects with acutely decompensated heart failure within the previous 30 days prior to screening. 5. Subjects with a left ventricular ejection fraction (LVEF) less than 40% or LV shortening fraction <0.2 within 3 months prior to randomization. 6. Subjects with acute myocardial infarction within 3 months prior to randomization. 7. Subjects with uncontrolled brady- or tachyarrhythmias (e.g. sinus arrest, complete heart block, atrial fibrillation or flutter, frequent runs of ventricular tachycardia); placement of dual chamber pacemakers and/or implantable defibrillators <60 days prior to randomization. 8. Subjects whose 6 Minute Walk Distance may be limited by conditions other than PAH related dyspnoea or fatigue, e.g. claudication from vascular insufficiency or significant arthritis. 9. Subjects who are currently receiving any forms of chronic treatment for PAH such as prostacyclin, PDE-5 inhibitors, endothelin-receptor antagonists, nitrates or nitric oxide donors (e.g. arginine supplement, nicorandil) in any form, protease inhibitors such as ritonavir and saquinavir, ketoconazole, itraconazole, and alpha blockers. Subjects previously receiving any of these drugs must have stopped use for a period of at least 1 month prior to screening, except in the case of endothelin receptor antagonists or prostacyclin (3 months). Note: Acute vasodilator response testing with any short acting vasodilators such as prostacyclin, inhaled NO and sildenafil during right heart catheterization is permitted. 10. Subjects who have previously failed on chronic treatment with sildenafil therapy (defined as those subjects who had no improvement and no change in symptoms on discontinuation of the medicine). 11. Subjects who have had a change of dose or class of standard background therapy used for treatment of PAH (e.g. oxygen, calcium channel blockers, digoxin, diuretics) within 30 days prior to randomization. Exception is treatment with anticoagulants where a patient?s dose may need to be adjusted based on INR. 12. Pregnant or lactating women. 13. Subjects with a history of pulmonary embolism verified by ventilation/perfusion scan, angiogram or spiral chest CT scan. 14. Subjects with known hereditary degenerative retinal disorders (such as retinitis pigmentosa) or history of non-arteritic anterior ischaemic optic neuropathy.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To demonstrate a dose response for 1 mg, 5 mg and 20 mg TID oral sildenafil for the treatment of subjects with PAH.;Secondary Objective: To assess the safety and tolerability of sildenafil (1 mg, 5 mg and 20 mg TID) after 12 weeks of treatment in subjects with PAH. To evaluate the effects of sildenafil (1 mg, 5 mg and 20 mg TID) on biomarkers of progression of PAH as measured by B-type natriuretic peptide (BNP)/pro-BNP levels and tricuspid annular plane systolic excursion (TAPSE) To determine the population pharmacokinetic parameters, and assess potential relationship of 6MWD, BNP/pro-BNP, TAPSE, PVRI and sildenafil exposure.;Primary end point(s): The change from baseline in the total distance walked during the 6MWT at Week 12 of the study
- Secondary Outcome Measures
Name Time Method