A multinational, multicentre, randomized, double-blind study to assess the efficacy and safety of oral sildenafil 20mg TID or placebo when added to Bosentan in the treatement of subjects, aged 18 years and above, with pulmonary arterial hypertension (PAH) - N/A

Phase 1

• Conditions: Pulmonary Arterial Hypertension; MedDRA version: 8.0 Level: LLT Classification code 10064911

• Registration Number: EUCTR2006-001464-23-GB
• Lead Sponsor: Pfizer Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2006-06-11
• Study Completion: 2013-08-20
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 103

Inclusion Criteria

1. Subjects aged 18 and above at the time of the screening visit who have any of the following types of pulmonary arterial hypertension and functional class, and for which bosentan therapy is indicated according to EU Marketing Authorisation:
· Idiopathic ‘Primary’ Pulmonary Arterial Hypertension (PAH)
. Pulmonary Hypertension secondary to Scleroderma.
· Subjects with WHO functional class III prior to initiation of bosentan therapy.
2. Subjects must have been treated continually with a stable dose of bosentan (62.5mg bid or 125mg bid) for a minimum of three months prior to randomization.
3. Subject with a mean pulmonary artery pressure =25 mmHg and a pulmonary capillarywedge pressure of < 15 mmHg at rest, via right heart catheterization within 12 months priorto randomization.
4. Subjects whose baseline 6-Minute Walk Test distrance is =100m and =400m.
5. Subjects who have given written informed consent to participate in the study before being screened for the study.
6. All women of childbearing potential must use adequate contraception (i.e. hormonal in conjunction with intrauterine device or barrier methods with spermicide) throughout the study and for the duration of their bosentan therapy or must be celibate or their partner must have had vasectomy. The screening serum pregnancy test must be negative. Women who have been surgically sterilized or are at least two years postmenopausal may be enrolled and do not need to use birth control.
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

1. PAH secondary to any aetiology including congenital heart disease other than those specified in the inclusion criteria.
2. With the exception of bosentan therapy, subjects who are currently receiving any forms of chronic treatment for PAH such as any formulations of prostacyclin, PDE-5 inhibitors, other endothelin-receptor antagonists, nitrates or nitric oxide donors (e.g. arginine supplements) including nicorandil in any form or any potent CYP3A4 inhibitors (e.g. Cyclosporin A and Glibenclamide). Note: Acute vasodilator response testing with any short acting vasodilators such as prostacyclin or inhaled NO during right heart catherization is permitted.
3. 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 randomization.
4. Subjects with acutely decompensated heart failure within 30 days prior to randomization.
5. Subjects with LV Ejection Fraction of <45% or LV shortening fraction of <0.2 within three months prior to randomization.
6. Subjects who have had a myocardial infarction within 6 months prior to randomization
7. Subjects who have had a change of dose or class of standard background therapy used for treatment of PAH (i.e. oxygen, calcium channel blockers, digoxin, diuretics) used for the treatment of PAH within 30 days prior to randomization. Note: a change in the dose or oral anticoagulant therapy within this timeframe to maintain the INR within the therapeutic range is acceptable.
8. Subjects with congenital heart disease (unless they fulfill inclusion 1.), pulmonaryhypertension due to thromboembolism, HIV or schistosomiasis.
9. Subjects who have undergone atrial septostomy within six months prior to randomization.
10. Subjects with uncontrolled brady- or tachyarrhythmias, placement of pacemakers orimplantable defibrillators <60 days prior to randomization.
11. Subjects whose 6 Minute Walk Test distance may be limited by conditions other than PAHrelated dyspnoea or fatigue e.g. claudication from vascular insufficiency or arthritis.
12. Pregnant or lactating women.
13. Subjects with a history or pulmonary embolism verified by ventilation/perfusion scan, angiogram or spiral chest CT scan.
14. Subjects with hypotension defined as systolic arterial pressure <90 mm Hg after sitting for 5 minutes at either screening or baseline.15. Subjects with known hereditary degenerative retinal disorders (such as retinitis pigmentosa)or history of non-arteritic ischemic optic neuropathy (NAION).
16. Subjects with history of chronic lung diseases / restrictive lung disease (e.g. COPD orscleroderma) with impairment of lung function as defined by TLC <60% and/or FEV1 =80% predicted within 30 days or randomization.
17. Subjects who have previously failed on bosentan or sildenafil th

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified