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To Assess The Efficacy and Safety Of Oral Sildenafil in the Treatment of Pulmonary Arterial Hypertension.

Primary Purpose

Pulmonary Arterial Hypertension

Status
Terminated
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Sildenafil citrate
Sildenafil citrate
Sildenafil citrate
Sildenafil citrate
Sponsored by
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension

Eligibility Criteria

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

Inclusion Criteria:

  • Subjects with PAH (i.e. IPAH or secondary to connective tissue disease or with surgical repair of ASD, VSD, PDA, aorto-pulmonary window) whose baseline six minute walk test distance is >/= 100 m and </= 450 m.
  • Subjects with a mean pulmonary artery pressure of >/= 25 mmHg and a pulmonary artery wedge pressure of </= 15 mmHg at rest via right heart catheterization performed within 12 weeks prior to randomization.

Exclusion Criteria:

  • Subjects whose 6 Minute Walk Distance may be limited by conditions other than PAH related dyspnoea or fatigue, e.g. claudication from vascular insufficiency or significant arthritis.
  • Subjects who are currently receiving any forms of chronic treatment for PAH such as prostacyclin, PDE-5 inhibitors, endothelin-receptor antagonists, nitrates or nitric oxide donors (e.g. arginine supplement, nicorandil) in any form, protease inhibitors such as ritonavir and saquinavir, ketoconazole, itraconazole, and alpha blockers. Subjects previously receiving any of these drugs must have stopped use for a period of at least 1 month prior to screening, except in the case of bosentan or prostacyclin (3 months).

Sites / Locations

  • Arizona Pulmonary Specialists, LTD
  • Medical College of Georgia
  • Atlanta Institute for Medical Research, Inc.
  • Chicago Heart Institute
  • The Care Group, LLC
  • The University of North Carolina at Chapel Hill
  • Mid Carolina Cardiology
  • Presbyterian Hospital
  • Baylor College of Medicine Pulmonary Section
  • St. Luke's Episcopal Hospital
  • University of Utah Sciences Center
  • CJW Chippenham Medical Center
  • Pulmonary Associates of Richmond, Inc.
  • Virginia Cardiovascular Specialists
  • Cardiovascular Associates of Virginia
  • Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
  • Hospital São Lucas da PUCRS
  • Instituto Dante Pazzanese de Cardiologia
  • Peta mnogoprofilna bolnitsa za aktivno lechenie, Klinika po kardiologia
  • Mnogoprofilna bolnitsa za aktivno lechenie i speshna meditsina "N.I.Pirogov"
  • Beijing Shijitan Hospital
  • Shanghai Pulmonology Hospital
  • Attikon Hospital
  • Care Hospital, The Institute of Medical Sciences
  • Mehta Hospital & Cardiopulmonary Care Center
  • Bankers Heart Institute
  • St. John's Medical College Hospital
  • Metro Multispeciality Hospital
  • IRCCS Policlinico San Matteo
  • Unita' di Ipertensione Polmonare, Dipartimento di Scienze Respiratorie e Cardiovascolari
  • P. Stradins Clinical University Hospital / Latvian Centre of Cardilogy
  • National Heart Institute
  • VU Medisch Centrum / afdeling Longziekten
  • Erasmus MC
  • Philippine General Hospital
  • Philippine Heart Center
  • Krakowski Szpital Specjalistyczny Im. Jana Pawla II w Krakowie
  • Samodzielny Publiczny Zaklad Opieki Zdrowotnej, Slaskie Centrum Chorob Serca
  • Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr. Victor Babes
  • Spitalul Clinic de Pneumoftiziologie
  • Scientific Center of Cardiovascular surgery n.a. A.N.Bakoulev RAMS
  • Scientific Center of Cardiovascular surgery n.a. A.N.Bakoulev RAMS
  • Division of Rheumatology Allergy and Immunology, Department of Medicine, Faculty of Medicine
  • Department of Medicine,
  • Norfolk and Norwich University Hospital
  • Room 224A Sir William Leech Centre

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Sildenafil High dose

Sildenafil Low dose

Sildenafil medium dose

Sildenafil - Open label Phase

Arm Description

Open label extension from week 12 to week 24.

Outcomes

Primary Outcome Measures

Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 12
6 MWT was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. Continuous pulse oximetry was conducted during the test for safety.

Secondary Outcome Measures

Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at Week 12
mPAP was measured using a pressure transducer positioned at the mid-axillary line.
Number of Participants With Clinical Worsening
Clinical worsening was defined as death; or lung transplantation; or hospitalization due to pulmonary hypertension; or initiation of prostacyclin therapy; or initiation of endothelin receptor antagonist therapy. (PAH=pulmonary arterial hypertension) Due to very low number of events of clinical worsening reported, the median days to clinical worsening could not be estimated.
Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12
Pulmonary arterial hypertension (PAH) Criteria for WHO Class: Class I (Participants without resulting limitation of physical activity);Class II (Participants with slight limitation of physical activity though comfortable at rest);Class III (Participants with marked limitation of physical activity,though comfortable at rest);Class IV(Participants with inability to carry out any physical activity without symptoms,manifest signs of right heart failure; dyspnoea and/or fatigue may even be present at rest; and discomfort is increased by any physical activity).
Change From Baseline in B-Type Natriuretic Peptide (BNP) at Week 12
BNP is a non-invasive biomarker and an indicator of progression of PAH/ right ventricular dysfunction in participants with PAH.
Change From Baseline in Pro-BNP at Week 12
Pro- BNP which is a precursor of BNP, is a non-invasive biomarker and an indicator of progression of PAH / RV dysfunction in participants with PAH.
Change From Baseline in TAPSE Measurement at Week 12
Tricuspid annular plane systolic excursion (TAPSE) was measured as the total displacement of the tricuspid annulus in cm from end diastole to end systole.TAPSE is an indicator of progression of PAH /right ventricular dysfunction. The baseline data for 33 participants were measured incorrectly and the results from the 33 participants (both baseline and post-baseline) were excluded from the analysis.
Change From Baseline in BORG Dyspnoea Score at Week 12
BORG dyspnoea scale is a 10-point scale where following scores stands for severity of dyspnoea: 0 (no breathlessness at all); 0.5 (very very slight [just noticeable]); 1 (very slight); 2 (slight breathlessness); 3 (moderate); 4 (some what severe); 5 (severe breathlessness); 7 (very severe breathlessness); 9 (very very severe [almost maximum] and 10 (maximum).

Full Information

First Posted
January 31, 2007
Last Updated
December 18, 2020
Sponsor
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00430716
Brief Title
To Assess The Efficacy and Safety Of Oral Sildenafil in the Treatment of Pulmonary Arterial Hypertension.
Official Title
A MULTINATIONAL, MULTICENTRE, RANDOMIZED, PARALLEL GROUP, DOUBLE-BLIND STUDY TO ASSESS THE EFFICACY AND SAFETY OF 1MG, 5MG AND 20 MG TID OF ORAL SILDENAFIL IN THE TREATMENT OF SUBJECTS AGED 18 YEARS AND OVER WITH PULMONARY ARTERIAL HYPERTENSION (PAH)
Study Type
Interventional

2. Study Status

Record Verification Date
December 2020
Overall Recruitment Status
Terminated
Why Stopped
This study was terminated at the recommendation of an independent Data Monitoring Committee. The decision was not based on any safety concerns.
Study Start Date
April 8, 2008 (Actual)
Primary Completion Date
May 25, 2010 (Actual)
Study Completion Date
May 25, 2010 (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.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
To demonstrate a dose response for 1 mg, 5 mg and 20 mg TID oral sildenafil for the treatment of subjects with PAH.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
130 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sildenafil High dose
Arm Type
Experimental
Arm Title
Sildenafil Low dose
Arm Type
Experimental
Arm Title
Sildenafil medium dose
Arm Type
Experimental
Arm Title
Sildenafil - Open label Phase
Arm Type
Experimental
Arm Description
Open label extension from week 12 to week 24.
Intervention Type
Drug
Intervention Name(s)
Sildenafil citrate
Intervention Description
oral, 20 mg, tid
Intervention Type
Drug
Intervention Name(s)
Sildenafil citrate
Intervention Description
oral 1 mg, tid
Intervention Type
Drug
Intervention Name(s)
Sildenafil citrate
Intervention Description
oral 5 mg, tid
Intervention Type
Drug
Intervention Name(s)
Sildenafil citrate
Intervention Description
oral 20 mg, tid
Primary Outcome Measure Information:
Title
Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 12
Description
6 MWT was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. Continuous pulse oximetry was conducted during the test for safety.
Time Frame
Baseline and Week 12
Secondary Outcome Measure Information:
Title
Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at Week 12
Description
mPAP was measured using a pressure transducer positioned at the mid-axillary line.
Time Frame
Baseline and Week 12
Title
Number of Participants With Clinical Worsening
Description
Clinical worsening was defined as death; or lung transplantation; or hospitalization due to pulmonary hypertension; or initiation of prostacyclin therapy; or initiation of endothelin receptor antagonist therapy. (PAH=pulmonary arterial hypertension) Due to very low number of events of clinical worsening reported, the median days to clinical worsening could not be estimated.
Time Frame
Baseline through Week 12
Title
Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12
Description
Pulmonary arterial hypertension (PAH) Criteria for WHO Class: Class I (Participants without resulting limitation of physical activity);Class II (Participants with slight limitation of physical activity though comfortable at rest);Class III (Participants with marked limitation of physical activity,though comfortable at rest);Class IV(Participants with inability to carry out any physical activity without symptoms,manifest signs of right heart failure; dyspnoea and/or fatigue may even be present at rest; and discomfort is increased by any physical activity).
Time Frame
Baseline and Week 12
Title
Change From Baseline in B-Type Natriuretic Peptide (BNP) at Week 12
Description
BNP is a non-invasive biomarker and an indicator of progression of PAH/ right ventricular dysfunction in participants with PAH.
Time Frame
Baseline and Week 12
Title
Change From Baseline in Pro-BNP at Week 12
Description
Pro- BNP which is a precursor of BNP, is a non-invasive biomarker and an indicator of progression of PAH / RV dysfunction in participants with PAH.
Time Frame
Baseline and Week 12
Title
Change From Baseline in TAPSE Measurement at Week 12
Description
Tricuspid annular plane systolic excursion (TAPSE) was measured as the total displacement of the tricuspid annulus in cm from end diastole to end systole.TAPSE is an indicator of progression of PAH /right ventricular dysfunction. The baseline data for 33 participants were measured incorrectly and the results from the 33 participants (both baseline and post-baseline) were excluded from the analysis.
Time Frame
Baseline and Week 12
Title
Change From Baseline in BORG Dyspnoea Score at Week 12
Description
BORG dyspnoea scale is a 10-point scale where following scores stands for severity of dyspnoea: 0 (no breathlessness at all); 0.5 (very very slight [just noticeable]); 1 (very slight); 2 (slight breathlessness); 3 (moderate); 4 (some what severe); 5 (severe breathlessness); 7 (very severe breathlessness); 9 (very very severe [almost maximum] and 10 (maximum).
Time Frame
Baseline and Week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects with PAH (i.e. IPAH or secondary to connective tissue disease or with surgical repair of ASD, VSD, PDA, aorto-pulmonary window) whose baseline six minute walk test distance is >/= 100 m and </= 450 m. Subjects with a mean pulmonary artery pressure of >/= 25 mmHg and a pulmonary artery wedge pressure of </= 15 mmHg at rest via right heart catheterization performed within 12 weeks prior to randomization. Exclusion Criteria: Subjects whose 6 Minute Walk Distance may be limited by conditions other than PAH related dyspnoea or fatigue, e.g. claudication from vascular insufficiency or significant arthritis. Subjects who are currently receiving any forms of chronic treatment for PAH such as prostacyclin, PDE-5 inhibitors, endothelin-receptor antagonists, nitrates or nitric oxide donors (e.g. arginine supplement, nicorandil) in any form, protease inhibitors such as ritonavir and saquinavir, ketoconazole, itraconazole, and alpha blockers. Subjects previously receiving any of these drugs must have stopped use for a period of at least 1 month prior to screening, except in the case of bosentan or prostacyclin (3 months).
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
Arizona Pulmonary Specialists, LTD
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
Medical College of Georgia
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
Atlanta Institute for Medical Research, Inc.
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30030
Country
United States
Facility Name
Chicago Heart Institute
City
Elk Grove Village
State/Province
Illinois
ZIP/Postal Code
60007
Country
United States
Facility Name
The Care Group, LLC
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
The University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Mid Carolina Cardiology
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Presbyterian Hospital
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Baylor College of Medicine Pulmonary Section
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
St. Luke's Episcopal Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah Sciences Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
CJW Chippenham Medical Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23225
Country
United States
Facility Name
Pulmonary Associates of Richmond, Inc.
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23225
Country
United States
Facility Name
Virginia Cardiovascular Specialists
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23225
Country
United States
Facility Name
Cardiovascular Associates of Virginia
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23230
Country
United States
Facility Name
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Hospital São Lucas da PUCRS
City
Porto Alegre
State/Province
RS
ZIP/Postal Code
90610-000
Country
Brazil
Facility Name
Instituto Dante Pazzanese de Cardiologia
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
04012-909
Country
Brazil
Facility Name
Peta mnogoprofilna bolnitsa za aktivno lechenie, Klinika po kardiologia
City
Sofia
ZIP/Postal Code
1233
Country
Bulgaria
Facility Name
Mnogoprofilna bolnitsa za aktivno lechenie i speshna meditsina "N.I.Pirogov"
City
Sofia
ZIP/Postal Code
1606
Country
Bulgaria
Facility Name
Beijing Shijitan Hospital
City
Beijing
ZIP/Postal Code
100038
Country
China
Facility Name
Shanghai Pulmonology Hospital
City
Shanghai
ZIP/Postal Code
200433
Country
China
Facility Name
Attikon Hospital
City
Haidari
State/Province
Athens
ZIP/Postal Code
12462
Country
Greece
Facility Name
Care Hospital, The Institute of Medical Sciences
City
Hyderabad
State/Province
Andhra Pradesh
ZIP/Postal Code
500 001
Country
India
Facility Name
Mehta Hospital & Cardiopulmonary Care Center
City
Ahmedabad
State/Province
Gujarat
ZIP/Postal Code
380 054
Country
India
Facility Name
Bankers Heart Institute
City
Vadodara
State/Province
Gujarat
ZIP/Postal Code
390 015
Country
India
Facility Name
St. John's Medical College Hospital
City
Bangalore
State/Province
Karnataka
ZIP/Postal Code
560 034
Country
India
Facility Name
Metro Multispeciality Hospital
City
Noida
State/Province
Uttar Pradesh
ZIP/Postal Code
201301
Country
India
Facility Name
IRCCS Policlinico San Matteo
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Facility Name
Unita' di Ipertensione Polmonare, Dipartimento di Scienze Respiratorie e Cardiovascolari
City
Roma
ZIP/Postal Code
00161
Country
Italy
Facility Name
P. Stradins Clinical University Hospital / Latvian Centre of Cardilogy
City
Riga
ZIP/Postal Code
LV - 1002
Country
Latvia
Facility Name
National Heart Institute
City
Kuala Lumpur
ZIP/Postal Code
50400
Country
Malaysia
Facility Name
VU Medisch Centrum / afdeling Longziekten
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Facility Name
Erasmus MC
City
Rotterdam
ZIP/Postal Code
3015 GE
Country
Netherlands
Facility Name
Philippine General Hospital
City
Manila City
ZIP/Postal Code
1000
Country
Philippines
Facility Name
Philippine Heart Center
City
Quezon City
ZIP/Postal Code
1100
Country
Philippines
Facility Name
Krakowski Szpital Specjalistyczny Im. Jana Pawla II w Krakowie
City
Krakow
ZIP/Postal Code
31-202
Country
Poland
Facility Name
Samodzielny Publiczny Zaklad Opieki Zdrowotnej, Slaskie Centrum Chorob Serca
City
Zabrze
ZIP/Postal Code
41-800
Country
Poland
Facility Name
Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr. Victor Babes
City
Timisoara
State/Province
Timis
Country
Romania
Facility Name
Spitalul Clinic de Pneumoftiziologie
City
Iasi
ZIP/Postal Code
700115
Country
Romania
Facility Name
Scientific Center of Cardiovascular surgery n.a. A.N.Bakoulev RAMS
City
Moscow
ZIP/Postal Code
117931
Country
Russian Federation
Facility Name
Scientific Center of Cardiovascular surgery n.a. A.N.Bakoulev RAMS
City
Moscow
ZIP/Postal Code
121552
Country
Russian Federation
Facility Name
Division of Rheumatology Allergy and Immunology, Department of Medicine, Faculty of Medicine
City
Amphoe Mueang
State/Province
Khon Kaen
ZIP/Postal Code
40002
Country
Thailand
Facility Name
Department of Medicine,
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Facility Name
Norfolk and Norwich University Hospital
City
Norwich
State/Province
Norfolk
ZIP/Postal Code
NR4 7UY
Country
United Kingdom
Facility Name
Room 224A Sir William Leech Centre
City
Newcastle Upon Tyne
State/Province
Tyne and Wear
ZIP/Postal Code
NE7 7DN
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Citations:
PubMed Identifier
28228114
Citation
Vizza CD, Sastry BK, Safdar Z, Harnisch L, Gao X, Zhang M, Lamba M, Jing ZC. Efficacy of 1, 5, and 20 mg oral sildenafil in the treatment of adults with pulmonary arterial hypertension: a randomized, double-blind study with open-label extension. BMC Pulm Med. 2017 Feb 23;17(1):44. doi: 10.1186/s12890-017-0374-x.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A1481244&StudyName=To%20Assess%20The%20Efficacy%20and%20Safety%20Of%20%20Oral%20Sildenafil%20in%20the%20Treatment%20of%20Pulmonary%20Arterial%20Hypertension.
Description
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To Assess The Efficacy and Safety Of Oral Sildenafil in the Treatment of Pulmonary Arterial Hypertension.

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