The Efficacy and Safety of Sildenafil Citrate Used in Combination With Intravenous Epoprostenol in PAH

Pulmonary Hypertension Clinical Trial

Official title:

A Multinational, Multi-Center, Randomised, Double-Bind, Placebo-Controlled, Parallel Group Study to Assess the Safety and Efficacy of a Subject Optimised Dose of Sildenafil Citrate (20, 40, or 80 mg. Sildenafil Citrate TID) Based on the Toleration, When Used in Combination With Intravenous Prostacyclin( Epoprostenol) in the Treatment of Pulmonary Arterial Hypertension.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00159861
• Other study ID #: A1481141
• Status: Completed
• Phase: Phase 3
• Start date: July 2003
• Est. completion date: January 2006

Study information

• Verified date: January 2021
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Determination of the effects of sildenafil citrate and epoprostenol when used in combination in patients with pulmonary arterial hypertension

Other known NCT identifiers

• NCT00147641

Recruitment information / eligibility

• Status: Completed
• Enrollment: 267
• Est. completion date: January 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• Patients with pulmonary arterial hypertension caused by primary PAH, associated with connective tissue disease or following surgical repair of a congenital heart lesion

Exclusion Criteria:

• PH other than PAH

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension

Intervention

Drug:
• Sildenafil citrate

Locations

Country	Name	City	State
Belgium	Pfizer Investigational Site	Leuven
Canada	Pfizer Investigational Site	Edmonton	Alberta
Canada	Pfizer Investigational Site	Montreal	Quebec
Canada	Pfizer Investigational Site	Ottawa	Ontario
Canada	Pfizer Investigational Site	Ottawa	Ontario
Canada	Pfizer Investigational Site	Toronto	Ontario
Czechia	Pfizer Investigational Site	Prague 2
Denmark	Pfizer Investigational Site	Kobenhavn
France	Pfizer Investigational Site	Clamart Cedex
France	Pfizer Investigational Site	Grenoble Cedex 09
France	Pfizer Investigational Site	Vandoeuvre Les Nancy
Israel	Pfizer Investigational Site	Petach Tikva
Italy	Pfizer Investigational Site	Bologna
Netherlands	Pfizer Investigational Site	Amsterdam
Netherlands	Pfizer Investigational Site	Nieuwegein
Spain	Pfizer Investigational Site	Barcelona
Spain	Pfizer Investigational Site	Madrid
United Kingdom	Pfizer Investigational Site	Glasgow
United Kingdom	Pfizer Investigational Site	Papworth Everard	Cambridgeshire
United States	Pfizer Investigational Site	Ann Arbor	Michigan
United States	Pfizer Investigational Site	Baltimore	Maryland
United States	Pfizer Investigational Site	Boston	Massachusetts
United States	Pfizer Investigational Site	Boston	Massachusetts
United States	Pfizer Investigational Site	Chicago	Illinois
United States	Pfizer Investigational Site	Cincinnati	Ohio
United States	Pfizer Investigational Site	Cincinnati	Ohio
United States	Pfizer Investigational Site	Cleveland	Ohio
United States	Pfizer Investigational Site	Denver	Colorado
United States	Pfizer Investigational Site	Denver	Colorado
United States	Pfizer Investigational Site	Durham	North Carolina
United States	Pfizer Investigational Site	Houston	Texas
United States	Pfizer Investigational Site	Kansas City	Kansas
United States	Pfizer Investigational Site	La Jolla	California
United States	Pfizer Investigational Site	Los Angeles	California
United States	Pfizer Investigational Site	Los Angeles	California
United States	Pfizer Investigational Site	Milwaukee	Wisconsin
United States	Pfizer Investigational Site	Milwaukee	Wisconsin
United States	Pfizer Investigational Site	Milwaukee	Wisconsin
United States	Pfizer Investigational Site	Nashville	Tennessee
United States	Pfizer Investigational Site	Nashville	Tennessee
United States	Pfizer Investigational Site	New Orleans	Louisiana
United States	Pfizer Investigational Site	New York	New York
United States	Pfizer Investigational Site	Omaha	Nebraska
United States	Pfizer Investigational Site	Omaha	Nebraska
United States	Pfizer Investigational Site	Pittsburgh	Pennsylvania
United States	Pfizer Investigational Site	Providence	Rhode Island
United States	Pfizer Investigational Site	Rochester	Minnesota
United States	Pfizer Investigational Site	Saint Louis	Missouri
United States	Pfizer Investigational Site	Salt Lake City	Utah
United States	Pfizer Investigational Site	San Diego	California
United States	Pfizer Investigational Site	Torrance	California
United States	Pfizer Investigational Site	Torrance	California

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.	Pfizer

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Czechia,  Denmark,  France,  Israel,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Epoprostenol Dose From Baseline Maintained for 6 Months	Number of subjects with changes in Epoprostenol dose from baseline maintained continuously for 6 months. Increased = Epoprostenol dose continuously more than 20% greater than core study Baseline for at least 6 months. Decrease = Epoprostenol dose continuously more than 20% less than core study Baseline for at least 6 months. No change = Epoprostenol dose change met neither Increase or Decrease criteria. Stopped = Epoprostenol dose stopped for at least 6 months.	Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Month 9, and at 3-month intervals through Month 69
Primary	Categorized Change From Baseline in 6-Minute Walking Distance	Number of subjects with categorized change in 6-minute walking distance. Distance that a subject could walk in 6-minutes at a comfortable pace with as many breaks as needed. Performed as close to trough levels of sildenafil as possible (just before dosing; at least 4 hours after the previous dose of study drug). Scores for categorized changes for missing visits were imputed as the worse score of its non-missing neighbors. If a visit was missing and there was no subsequent score, the score was coded to missing.	1 Year, 2 Year, 3 Year
Secondary	Survival Status	Yearly survival status: number of subjects who survived, discontinued, and died. Analysis includes post-treatment visit data from subjects who discontinued study treatment. Time to death was taken relative to the first dose of study treatment in A1481141, and was censored on the last day the subject was known to be alive in A1481141 or A1481153.	1, 2, 3, 4, and 5 years
Secondary	Change in Pulmonary Hypertension Criteria for Functional Capacity and Therapeutic Class	Pulmonary hypertension (PH) criteria: Class I: PH without limitation of physical activity (PA) (no undue dyspnea, fatigue, chest pain, near syncope); Class II: PH with slight limitation in PA, comfortable at rest, ordinary PA causes undue dyspnea, fatigue, chest pain, near syncope; Class III: PH with marked limitation in PA, comfortable at rest, less than ordinary activity causes undue dyspnea, fatigue, chest pain or syncope; Class IV: PH with inability to carry out PA without symptoms, signs of right heart failure, dyspnea or fatigue may be present at rest, discomfort increased by any PA.	1 Year, 2 Year, 3 Year
Secondary	Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36)	Subject-rated measure of health status comprised of 36 items: 8 subscale scores (physical functioning, role limitations due to physical health problems, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems, and mental health), 2 summary scores (physical component and mental component), and a self-evaluated change in health status. Subscale and summary scores range: 0-100. Higher subscale and summary scores = better health status. Change from baseline = score at observation minus score at baseline.	Baseline, Month 15, Month 27, Month 39
Secondary	Change From Baseline in European Quality of Life Scale (EuroQol) 5-Dimensions (EQ-5D): Utility Index Score	EQ-5D: subject rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.	Baseline, Month 15, Month 27, Month 39
Secondary	Change From Baseline in European Quality of Life (EuroQol) Visual Analogue Scale (EQ-5D VAS): Current Health State Score	EQ-5D: subject rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state.	Baseline, Month 15, Month 27, Month 39
Secondary	Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36): Reported Health Transition Score	Subject-rated measure of health status (36 items): 8 subscale scores (physical functioning, role limitations due to physical health problems, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems, mental health), 2 summary scores (physical component, mental component), and a self-evaluated change in health status. Change from Baseline in SF-36 Health Transition score at each visit. I=much better than 1 year ago; II=somewhat better than 1 year ago; III=about the same as 1 year ago; IV=somewhat worse than 1 year ago; V=much worse than 1 year ago	Baseline, Month 15, Month 27, Month 39
Secondary	Change From Baseline in BORG Dyspnea Score	BORG Dyspnea score: change from core study Baseline. Subject rating of maximum degree of dyspnea experienced at any time during the 6-Minute Walk Test. Range: 0 (no breathlessness at all) to 10 (maximum breathlessness).	Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Month 9, Month 12, Month 15, Month 18, Month 21, Month 24, Month 27, Month 30, Month 33, Month 36

External Links

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