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

Primary Purpose

Pulmonary Hypertension

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Sildenafil citrate
Sponsored by
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Hypertension

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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
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).

Full Information

First Posted
September 8, 2005
Last Updated
January 28, 2021
Sponsor
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Collaborators
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT00159861
Brief Title
The Efficacy and Safety of Sildenafil Citrate Used in Combination With Intravenous Epoprostenol in PAH
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.
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
July 2003 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
January 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Collaborators
Pfizer

4. Oversight

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Hypertension

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
267 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Sildenafil citrate
Primary Outcome Measure Information:
Title
Categorized Change From Baseline in 6-Minute Walking Distance
Description
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.
Time Frame
1 Year, 2 Year, 3 Year
Secondary Outcome Measure Information:
Title
Survival Status
Description
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.
Time Frame
1, 2, 3, 4, and 5 years
Title
Change in Pulmonary Hypertension Criteria for Functional Capacity and Therapeutic Class
Description
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.
Time Frame
1 Year, 2 Year, 3 Year
Title
Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36)
Description
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.
Time Frame
Baseline, Month 15, Month 27, Month 39
Title
Change From Baseline in European Quality of Life Scale (EuroQol) 5-Dimensions (EQ-5D): Utility Index Score
Description
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.
Time Frame
Baseline, Month 15, Month 27, Month 39
Title
Change From Baseline in European Quality of Life (EuroQol) Visual Analogue Scale (EQ-5D VAS): Current Health State Score
Description
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.
Time Frame
Baseline, Month 15, Month 27, Month 39
Title
Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36): Reported Health Transition Score
Description
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
Time Frame
Baseline, Month 15, Month 27, Month 39
Title
Change From Baseline in BORG Dyspnea Score
Description
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).
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
Other Pre-specified Outcome Measures:
Title
Change in Epoprostenol Dose From Baseline Maintained for 6 Months
Description
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.
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Pfizer Investigational Site
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
Pfizer Investigational Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Pfizer Investigational Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90073
Country
United States
Facility Name
Pfizer Investigational Site
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Pfizer Investigational Site
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
Pfizer Investigational Site
City
Torrance
State/Province
California
ZIP/Postal Code
90509
Country
United States
Facility Name
Pfizer Investigational Site
City
Denver
State/Province
Colorado
ZIP/Postal Code
80220
Country
United States
Facility Name
Pfizer Investigational Site
City
Denver
State/Province
Colorado
ZIP/Postal Code
80262
Country
United States
Facility Name
Pfizer Investigational Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Pfizer Investigational Site
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Pfizer Investigational Site
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Pfizer Investigational Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Pfizer Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Pfizer Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Pfizer Investigational Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Pfizer Investigational Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Pfizer Investigational Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Pfizer Investigational Site
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68105
Country
United States
Facility Name
Pfizer Investigational Site
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198-2125
Country
United States
Facility Name
Pfizer Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Pfizer Investigational Site
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Pfizer Investigational Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Pfizer Investigational Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267-0769
Country
United States
Facility Name
Pfizer Investigational Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Pfizer Investigational Site
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Pfizer Investigational Site
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
Pfizer Investigational Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-5735
Country
United States
Facility Name
Pfizer Investigational Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Pfizer Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Pfizer Investigational Site
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84143
Country
United States
Facility Name
Pfizer Investigational Site
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53215
Country
United States
Facility Name
Pfizer Investigational Site
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Pfizer Investigational Site
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53277
Country
United States
Facility Name
Pfizer Investigational Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Pfizer Investigational Site
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2B7
Country
Canada
Facility Name
Pfizer Investigational Site
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4E9
Country
Canada
Facility Name
Pfizer Investigational Site
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4W7
Country
Canada
Facility Name
Pfizer Investigational Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2N2
Country
Canada
Facility Name
Pfizer Investigational Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
Pfizer Investigational Site
City
Prague 2
ZIP/Postal Code
128 08
Country
Czechia
Facility Name
Pfizer Investigational Site
City
Kobenhavn
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Pfizer Investigational Site
City
Clamart Cedex
ZIP/Postal Code
92141
Country
France
Facility Name
Pfizer Investigational Site
City
Grenoble Cedex 09
ZIP/Postal Code
38043
Country
France
Facility Name
Pfizer Investigational Site
City
Vandoeuvre Les Nancy
Country
France
Facility Name
Pfizer Investigational Site
City
Petach Tikva
ZIP/Postal Code
49100
Country
Israel
Facility Name
Pfizer Investigational Site
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Pfizer Investigational Site
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Facility Name
Pfizer Investigational Site
City
Nieuwegein
ZIP/Postal Code
3435CM
Country
Netherlands
Facility Name
Pfizer Investigational Site
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Pfizer Investigational Site
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Pfizer Investigational Site
City
Papworth Everard
State/Province
Cambridgeshire
ZIP/Postal Code
CB3 8RE
Country
United Kingdom
Facility Name
Pfizer Investigational Site
City
Glasgow
ZIP/Postal Code
G11 6NT
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
24815795
Citation
Simonneau G, Rubin LJ, Galie N, Barst RJ, Fleming TR, Frost A, Engel P, Kramer MR, Serdarevic-Pehar M, Layton GR, Sitbon O, Badesch DB; PACES Study Group. Long-term sildenafil added to intravenous epoprostenol in patients with pulmonary arterial hypertension. J Heart Lung Transplant. 2014 Jul;33(7):689-97. doi: 10.1016/j.healun.2014.02.019. Epub 2014 Feb 22.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A1481141&StudyName=The+Efficacy+and+Safety+of+Sildenafil+Citrate+Used+in+Combination+with+Intravenous+Epoprostenol+in+PAH+
Description
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The Efficacy and Safety of Sildenafil Citrate Used in Combination With Intravenous Epoprostenol in PAH

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