Hypertension, Pulmonary
Conditions
Brief summary
To evaluate the effect of three doses of oral sildenafil (20, 40 and 80 mg three times a day \[TID\]) on exercise capacity, as measured by the 6-Minute Walk test, as well as the safety and tolerability, after 12 weeks of treatment in subjects with pulmonary arterial hypertension who are aged 18 years and over. To investigate the plasma concentration-effect relationship and to determine the population pharmacokinetic (PK) parameters.
Interventions
DRUGsildenafil
sildenafil 40 mg by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks
DRUGplacebo
placebo by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Included patients had primary pulmonary arterial hypertension, pulmonary hypertension secondary to connective tissue disease, or pulmonary hypertension with surgical repair at least 5 years previously; a mean pulmonary artery pressure greater than or equal to 25 mmHg and a pulmonary artery wedge pressure of less than or equal to 15 mmHg at rest, via right heart catheterisation within 21 days prior to randomisation; and a baseline 6-Minute Walk test distance of 100 m to 450 m.
Exclusion criteria
Subjects with congenital heart disease, pulmonary hypertension due to thromboembolism, HIV, chronic obstructive airway disease, congestive heart failure or schistosomiasis; subjects with significant (ie \> 2+) valvular disease other than tricuspid regurgitation or pulmonary regurgitation; and acutely decompensated heart failure within the previous 30 days; subjects with pulmonary hypertension secondary to any other etiology other than those specified in the inclusion criteria.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in exercise capacity, as measured by distance walked in six minutes (6-Minute Walk test). | Week 12 |
Secondary
| Measure | Time frame |
|---|---|
| Change from baseline in mean pulmonary arterial pressure | Week 12 |
| Time from randomisation to the first occurrence of clinical worsening (death or lung transplantation or hospitalisation due to pulmonary hypertension or initiation of prostacyclin therapy or initiation of bosentan therapy) | Week 0 to 12 |
| Change from baseline in the BORG dyspnoea score | Week 12 |
| Change from baseline in the 8 dimensions of SF-36 (Physical functioning, Role functioning, Bodily pain, General health, Vitality, Social functioning, Mental health and Reported health transition) | Week 4 and Week 12 |
| Change from baseline in pulmonary hypertension criteria for functional capacity and therapeutic class | Week 12 |
| Patient overall preference assessment | Week 12 |
| Change in Chronic Use of Background Therapy for Pulmonary Arterial Hypertension | throughout the study |
| Change from baseline in hemodynamic parameters | Week 12 |
| Change from baseline at Weeks 4 and 12 in the 5 dimensions of ED5Q (Mobility, Self care, Usual Activities, Pain/Discomfort and Anxiety/Depression) | Week 4 and Week 12 |
Countries
Australia, Belgium, Brazil, Czechia, Denmark, France, Germany, Hong Kong, Hungary, Israel, Italy, Malaysia, Mexico, Netherlands, Norway, Poland, Singapore, South Africa, South Korea, Spain, Sweden, United Kingdom, United States
Outcome results
None listed