Clinical trial NCT00644605: A Study to Assess the Efficacy and Safety of 20, 40, and 80mg of Sildenafil Three Times a Day in the Treatment of Pulmonary Arterial Hypertension
Official title: A Multinational, Multi-centre, Randomised, Double-blind, Double-dummy, Placebo-controlled Study to Assess the Efficacy and Safety of 20, 40, and 80mg TID Sildenafil in the Treatment of Pulmonary Arterial Hypertension in Subjects Aged 18 Years and Over
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension, Pulmonary
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2008-03-27
Enrollment: 275
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline in exercise capacity, as measured by distance walked in six minutes (6-Minute Walk test).
timeFrame: Week 12
Secondary outcomes:
measure: Change from baseline in mean pulmonary arterial pressure
timeFrame: Week 12
measure: 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)
timeFrame: Week 0 to 12
measure: Change from baseline in the BORG dyspnoea score
timeFrame: Week 12
measure: Change from baseline in pulmonary hypertension criteria for functional capacity and therapeutic class
timeFrame: Week 12
measure: 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)
timeFrame: Week 4 and Week 12
measure: Change from baseline at Weeks 4 and 12 in the 5 dimensions of ED5Q (Mobility, Self care, Usual Activities, Pain/Discomfort and Anxiety/Depression)
timeFrame: Week 4 and Week 12
measure: Patient overall preference assessment
timeFrame: Week 12
measure: Change in Chronic Use of Background Therapy for Pulmonary Arterial Hypertension
timeFrame: throughout the study
measure: Change from baseline in hemodynamic parameters
timeFrame: Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Pfizer Investigational Site
state: Alabama
city: Birmingham
country: United States
facility: Pfizer Investigational Site
state: Alabama
city: Birmingham
country: United States
facility: Pfizer Investigational Site
state: Alabama
city: La Jolla
country: United States
facility: Pfizer Investigational Site
state: California
city: La Jolla
country: United States
facility: Pfizer Investigational Site
state: California
city: Los Angeles
country: United States
facility: Pfizer Investigational Site
state: California
city: Los Angeles
country: United States
facility: Pfizer Investigational Site
state: California
city: Los Angeles
country: United States
facility: Pfizer Investigational Site
state: California
city: San Diego
country: United States
facility: Pfizer Investigational Site
state: California
city: Torrance
country: United States
facility: Pfizer Investigational Site
state: California
city: Torrance
country: United States
facility: Pfizer Investigational Site
state: California
city: Aurora
country: United States
facility: Pfizer Investigational Site
state: Colorado
city: Denver
country: United States
facility: Pfizer Investigational Site
state: Colorado
city: Chicago
country: United States
facility: Pfizer Investigational Site
state: Illinois
city: Shreveport
country: United States
facility: Pfizer Investigational Site
state: Louisiana
city: Baltimore
country: United States
facility: Pfizer Investigational Site
state: Maryland
city: Boston
country: United States
facility: Pfizer Investigational Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Pfizer Investigational Site
state: Michigan
city: Rochester
country: United States
facility: Pfizer Investigational Site
state: Minnesota
city: New York
country: United States
facility: Pfizer Investigational Site
state: New York
city: Durham
country: United States
facility: Pfizer Investigational Site
state: North Carolina
city: Nashville
country: United States
facility: Pfizer Investigational Site
state: Tennessee
city: Houston
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Milwaukee
country: United States
facility: Pfizer Investigational Site
state: Wisconsin
city: Darlinghurst
country: Australia
facility: Pfizer Investigational Site
state: New South Wales
city: Melbourne
country: Australia
facility: Pfizer Investigational Site
state: Victoria
city: Bruxelles
country: Belgium
facility: Pfizer Investigational Site
city: Leuven
country: Belgium
facility: Pfizer Investigational Site
city: Sao Paulo
country: Brazil
facility: Pfizer Investigational Site
state: SP
city: Prague 4
country: Czechia
facility: Pfizer Investigational Site
city: Prague 4
country: Czechia
facility: Pfizer Investigational Site
city: Kobenhavn
country: Denmark
facility: Pfizer Investigational Site
city: Clamart
country: France
facility: Pfizer Investigational Site
city: Berlin
country: Germany
facility: Pfizer Investigational Site
city: Giessen
country: Germany
facility: Pfizer Investigational Site
city: Giessen
country: Germany
facility: Pfizer Investigational Site
city: Hannover
country: Germany
facility: Pfizer Investigational Site
city: Leipzig
country: Germany
facility: Pfizer Investigational Site
city: Shatin N T
country: Hong Kong
facility: Pfizer Investigational Site
city: Budapest
country: Hungary
facility: Pfizer Investigational Site
state: Pest
city: Zalaegerszeg
country: Hungary
facility: Pfizer Investigational Site
state: Zala
city: Petach Tikva
country: Israel
facility: Pfizer Investigational Site
city: Tel Hashomer
country: Israel
facility: Pfizer Investigational Site
city: Bologna
country: Italy
facility: Pfizer Investigational Site
city: Pisa
country: Italy
facility: Pfizer Investigational Site
city: Pisa
country: Italy
facility: Pfizer Investigational Site
city: Suwon
country: Korea, Republic of
facility: Pfizer Investigational Site
city: Kuala Lumpur
country: Malaysia
facility: Pfizer Investigational Site
city: Tlalpan
country: Mexico
facility: Pfizer Investigational Site
city: Amsterdam
country: Netherlands
facility: Pfizer Investigational Site
city: Oslo
country: Norway
facility: Pfizer Investigational Site
city: Katowice
country: Poland
facility: Pfizer Investigational Site
city: Warszawa
country: Poland
facility: Pfizer Investigational Site
city: Warszawa
country: Poland
facility: Pfizer Investigational Site
city: Zabrze
country: Poland
facility: Pfizer Investigational Site
city: Singapore
country: Singapore
facility: Pfizer Investigational Site
city: Cape Town
country: South Africa
facility: Pfizer Investigational Site
city: Johannesburg
country: South Africa
facility: Pfizer Investigational Site
city: Parow
country: South Africa
facility: Pfizer Investigational Site
city: Barcelona
country: Spain
facility: Pfizer Investigational Site
city: Barcelona
country: Spain
facility: Pfizer Investigational Site
city: Madrid
country: Spain
facility: Pfizer Investigational Site
city: Goteborg
country: Sweden
facility: Pfizer Investigational Site
city: Molndal
country: Sweden
facility: Pfizer Investigational Site
city: Papworth Everard
country: United Kingdom
facility: Pfizer Investigational Site
state: Cambridgeshire
city: Sheffield
country: United Kingdom
facility: Pfizer Investigational Site
state: South Yorkshire
city: Glasgow
country: United Kingdom
facility: Pfizer Investigational Site
city: HIGH Heaton, Newcastle-upon-tyne
country: United Kingdom
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Wirostko BM, Tressler C, Hwang LJ, Burgess G, Laties AM. Ocular safety of sildenafil citrate when administered chronically for pulmonary arterial hypertension: results from phase III, randomised, double masked, placebo controlled trial and open label extension. BMJ. 2012 Feb 21;344:e554. doi: 10.1136/bmj.e554.