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

January 28, 2021 updated by: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

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.

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

267

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Leuven, Belgium, 3000
        • Pfizer Investigational Site
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2B7
        • Pfizer Investigational Site
    • Ontario
      • Ottawa, Ontario, Canada, K1Y 4W7
        • Pfizer Investigational Site
      • Ottawa, Ontario, Canada, K1Y 4E9
        • Pfizer Investigational Site
      • Toronto, Ontario, Canada, M5G 2N2
        • Pfizer Investigational Site
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Pfizer Investigational Site
  • Czechia
      • Prague 2, Czechia, 128 08
        • Pfizer Investigational Site
  • Denmark
      • Kobenhavn, Denmark, 2100
        • Pfizer Investigational Site
  • France
      • Clamart Cedex, France, 92141
        • Pfizer Investigational Site
      • Grenoble Cedex 09, France, 38043
        • Pfizer Investigational Site
      • Vandoeuvre Les Nancy, France
        • Pfizer Investigational Site
  • Israel
      • Petach Tikva, Israel, 49100
        • Pfizer Investigational Site
  • Italy
      • Bologna, Italy, 40138
        • Pfizer Investigational Site
  • Netherlands
      • Amsterdam, Netherlands, 1081 HV
        • Pfizer Investigational Site
      • Nieuwegein, Netherlands, 3435CM
        • Pfizer Investigational Site
  • Spain
      • Barcelona, Spain, 08036
        • Pfizer Investigational Site
      • Madrid, Spain, 28041
        • Pfizer Investigational Site
  • United Kingdom
      • Glasgow, United Kingdom, G11 6NT
        • Pfizer Investigational Site
    • Cambridgeshire
      • Papworth Everard, Cambridgeshire, United Kingdom, CB3 8RE
        • Pfizer Investigational Site
  • United States
    • California
      • La Jolla, California, United States, 92037
        • Pfizer Investigational Site
      • Los Angeles, California, United States, 90073
        • Pfizer Investigational Site
      • Los Angeles, California, United States, 90033
        • Pfizer Investigational Site
      • San Diego, California, United States, 92103
        • Pfizer Investigational Site
      • Torrance, California, United States, 90502
        • Pfizer Investigational Site
      • Torrance, California, United States, 90509
        • Pfizer Investigational Site
    • Colorado
      • Denver, Colorado, United States, 80220
        • Pfizer Investigational Site
      • Denver, Colorado, United States, 80262
        • Pfizer Investigational Site
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Pfizer Investigational Site
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Pfizer Investigational Site
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Pfizer Investigational Site
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Pfizer Investigational Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Pfizer Investigational Site
      • Boston, Massachusetts, United States, 02111
        • Pfizer Investigational Site
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Pfizer Investigational Site
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Pfizer Investigational Site
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Pfizer Investigational Site
    • Nebraska
      • Omaha, Nebraska, United States, 68105
        • Pfizer Investigational Site
      • Omaha, Nebraska, United States, 68198-2125
        • Pfizer Investigational Site
    • New York
      • New York, New York, United States, 10032
        • Pfizer Investigational Site
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Pfizer Investigational Site
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Pfizer Investigational Site
      • Cincinnati, Ohio, United States, 45267-0769
        • Pfizer Investigational Site
      • Cleveland, Ohio, United States, 44195
        • Pfizer Investigational Site
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Pfizer Investigational Site
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Pfizer Investigational Site
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Pfizer Investigational Site
      • Nashville, Tennessee, United States, 37232-5735
        • Pfizer Investigational Site
    • Texas
      • Houston, Texas, United States, 77030
        • Pfizer Investigational Site
    • Utah
      • Salt Lake City, Utah, United States, 84143
        • Pfizer Investigational Site
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Pfizer Investigational Site
      • Milwaukee, Wisconsin, United States, 53215
        • Pfizer Investigational Site
      • Milwaukee, Wisconsin, United States, 53277
        • Pfizer Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Categorized Change From Baseline in 6-Minute Walking Distance
Time Frame: 1 Year, 2 Year, 3 Year
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Survival Status
Time Frame: 1, 2, 3, 4, and 5 years
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
Change in Pulmonary Hypertension Criteria for Functional Capacity and Therapeutic Class
Time Frame: 1 Year, 2 Year, 3 Year
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
Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36)
Time Frame: Baseline, Month 15, Month 27, Month 39
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
Change From Baseline in European Quality of Life Scale (EuroQol) 5-Dimensions (EQ-5D): Utility Index Score
Time Frame: Baseline, Month 15, Month 27, Month 39
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
Change From Baseline in European Quality of Life (EuroQol) Visual Analogue Scale (EQ-5D VAS): Current Health State Score
Time Frame: Baseline, Month 15, Month 27, Month 39
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
Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36): Reported Health Transition Score
Time Frame: Baseline, Month 15, Month 27, Month 39
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
Change From Baseline in BORG Dyspnea Score
Time Frame: 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
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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Epoprostenol Dose From Baseline Maintained for 6 Months
Time Frame: Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Month 9, and at 3-month intervals through Month 69
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Collaborators

Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2003

Study Completion (Actual)

January 1, 2006

Study Registration Dates

First Submitted

September 8, 2005

First Submitted That Met QC Criteria

September 11, 2005

First Posted (Estimate)

September 12, 2005

Study Record Updates

Last Update Posted (Actual)

February 1, 2021

Last Update Submitted That Met QC Criteria

January 28, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A1481141

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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