search
Back to results

Assess the Efficacy and Safety of Sildenafil When Added to Bosentan in the Treatment of Pulmonary Arterial Hypertension

Primary Purpose

Pulmonary Arterial Hypertension

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Bosentan
Placebo
Bosentan
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 aged 18 and over above with PAH and for which bosentan therapy is indicated according to national license Subjects with a mean pulmonary artery pressure of >25mmHg and a pulmonary artery wedge pressure of <15mmHg at rest via right heart catheterization within 3 years prior to randomization. Subjects whose baseline 6 Minute Walk Test distance is >100m and < 450m. Exclusion Criteria: PAH secondary to any aetiology including congenital heart disease other than those specified in the inclusion criteria Subjects whose 6 Minute Walk Test may be limited by conditions other than PAH related dyspnoea or fatigue eg. claudication from vascular insufficiency or arthritis.

Sites / Locations

  • West Los Angeles VA Healthcare, Pulmonary Hypertension Program
  • Henry Ford Hospital
  • Allegheny General Hospital
  • Baylor College of Medicine
  • The Methodist Hospital
  • Diagnostics Research Group
  • St. Vincents Hospital
  • The Prince Charles Hospital
  • Vseobecna fakultni nemocnice v Praze
  • Institut klinicke a experimentalni mediciny, Klinika kardiologie
  • Clinique des Maladies Respiratoires
  • Hopital Claude Huriez
  • Hopital Adules Brabois
  • Unfallkrankenhaus Berlin, Klinik fuer Innere Medizin
  • II. Medizinische Klinik, Kardiologie, Angiologie und Pneumologie
  • Universitaetsklinikum Essen, Zentrum fuer Innere Medizin, Klinik fuer Kardiologie
  • Universitaetsklinikum Giessen und Marburg GmbH, Standort Giessen
  • Medizinische Hochschule Hannover
  • Universitaetsklinikum des Saarlandes, Innere Medizin V
  • Medizinische Klinik und Poliklinik I, Universitaetsklinikum Leipzig
  • Med. Klinik u. Poliklinik I der LMU Muenchen, Klinikum Grosshadern
  • Praxis fuer Innere Medizin, Kardiologie und Angiologie
  • Missionsaerztliche Klinik Wuerzburg, Gemeinnuetzige Gesellschaft mbH
  • Attikon Hospital
  • Rambam Medical Center
  • Rabin Medical Centre
  • Cardiologia, Azienda Ospedaliera Monaldi, Seconda Università di Napoli
  • Unita' di Ipertensione Polmonare, Dipartimento di Scienze Respiratorie e Cardiovascolari
  • Department of Surgery, National Taiwan University Hospital
  • PVDU

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

placebo

Active

Arm Description

Outcomes

Primary Outcome Measures

Change From Baseline in the Total Distance Walked During 6 Minute Walk Time (6MWT) at Week 12
6MWT is 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

Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Class in Participants With PAH at Week 12 LOCF
WHO functional classification for PAH range from Class I (no limitation in physical activity, no dyspnea with normal activity) to Class IV (can not perform a physical activity without any symptoms, dyspnea at rest). Improvement=reduction in functional class; deterioration = increase in functional class, no change = no change in functional class.
Clinical Worsening Events
No survival analysis was carried out for the study due to very few events of clinical worsening. Hence, we present a summary of clinical worsening events instead. Events of clinical worsening were categorized as (A). Death, (B). Heart/lung transplantation, (C). Hospitalization due to pulmonary arterial hypertension (PAH), and (D). Clinical deterioration of PAH requiring additional therapy.
Change From Baseline in Borg Dyspnea Score at Week 12
Borg dyspnea scale is a 10-point scale where following scores stands for severity of dyspnea: 0 (no breathlessness at all); 0.5 (very very slight [just noticeable]); (very slight); (slight breathlessness); (moderate); 4 (some what severe); 5 (severe breathlessness); 7 (very severe breathlessness); 9 (very very severe [almost maximum]); and 10 (maximum).
One Year Survival Probability From the Start of Sildenafil Treatment.
The survival probability of all participants up to 1-year post start of Sildenafil treatment; for participants who were randomized to Sildenafil, this was the week 52 from randomization, and for participants who were originally randomized to Placebo group, this was the Week 64 from Baseline (Week 52 from Week 12, when the first dose of Sildenafil was administered to these participants). Those participants who discontinued from the study prior to 1 year after start of sildenafil were considered as censored at the time of discontinuation and those who discontinued from the study post 1-year after start of sildenafil were considered as censored at the time of 1-year post start of sildenafil.
One Year Survival From the Start of Sildenafil Treatment.
The survival status of all participants who discontinued from the study, including those participants who discontinued during the double-blind phase, was to be assessed at one year post their Week 12 visit/ End of treatment visit.

Full Information

First Posted
May 5, 2006
Last Updated
January 28, 2021
Sponsor
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT00323297
Brief Title
Assess the Efficacy and Safety of Sildenafil When Added to Bosentan in the Treatment of Pulmonary Arterial Hypertension
Official Title
A Multinational, Multicentre, Randomized, Double-blind Study To Assess The Efficacy And Safety Of Oral Sildenafil 20mg Tid Or Placebo When Added To Bosentan In The Treatment Of Subjects, Aged 18 Years And Above, With Pulmonary Arterial Hypertension (Pah)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
September 2006 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
August 2013 (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 assess the efficacy and safety of sildenafil when added to patients with PAH who are taking bosentan as all or part of their background therapy.

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 ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
105 (Actual)

8. Arms, Groups, and Interventions

Arm Title
placebo
Arm Type
Placebo Comparator
Arm Title
Active
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Bosentan
Intervention Description
Bosentan + Placebo for 12 weeks of the study (double blind), then 12 months open label phase (bosentan + sildenafil)
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Bosentan + Placebo for 12 weeks of the study (double blind), then 12 months open label phase (bosentan + sildenafil)
Intervention Type
Drug
Intervention Name(s)
Bosentan
Intervention Description
Bosentan + Sildenafil for 12 weeks of the study (double blind), then 12 months open label phase
Intervention Type
Drug
Intervention Name(s)
Sildenafil Citrate
Intervention Description
Bosentan + Sildenafil for 12 weeks of the study (double blind), then 12 months open label phase
Primary Outcome Measure Information:
Title
Change From Baseline in the Total Distance Walked During 6 Minute Walk Time (6MWT) at Week 12
Description
6MWT is 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
Week 12
Secondary Outcome Measure Information:
Title
Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Class in Participants With PAH at Week 12 LOCF
Description
WHO functional classification for PAH range from Class I (no limitation in physical activity, no dyspnea with normal activity) to Class IV (can not perform a physical activity without any symptoms, dyspnea at rest). Improvement=reduction in functional class; deterioration = increase in functional class, no change = no change in functional class.
Time Frame
Week 12
Title
Clinical Worsening Events
Description
No survival analysis was carried out for the study due to very few events of clinical worsening. Hence, we present a summary of clinical worsening events instead. Events of clinical worsening were categorized as (A). Death, (B). Heart/lung transplantation, (C). Hospitalization due to pulmonary arterial hypertension (PAH), and (D). Clinical deterioration of PAH requiring additional therapy.
Time Frame
Week 12
Title
Change From Baseline in Borg Dyspnea Score at Week 12
Description
Borg dyspnea scale is a 10-point scale where following scores stands for severity of dyspnea: 0 (no breathlessness at all); 0.5 (very very slight [just noticeable]); (very slight); (slight breathlessness); (moderate); 4 (some what severe); 5 (severe breathlessness); 7 (very severe breathlessness); 9 (very very severe [almost maximum]); and 10 (maximum).
Time Frame
Week 12
Title
One Year Survival Probability From the Start of Sildenafil Treatment.
Description
The survival probability of all participants up to 1-year post start of Sildenafil treatment; for participants who were randomized to Sildenafil, this was the week 52 from randomization, and for participants who were originally randomized to Placebo group, this was the Week 64 from Baseline (Week 52 from Week 12, when the first dose of Sildenafil was administered to these participants). Those participants who discontinued from the study prior to 1 year after start of sildenafil were considered as censored at the time of discontinuation and those who discontinued from the study post 1-year after start of sildenafil were considered as censored at the time of 1-year post start of sildenafil.
Time Frame
One year from the time of starting sildenafil
Title
One Year Survival From the Start of Sildenafil Treatment.
Description
The survival status of all participants who discontinued from the study, including those participants who discontinued during the double-blind phase, was to be assessed at one year post their Week 12 visit/ End of treatment visit.
Time Frame
One year from the time of starting sildenafil

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects aged 18 and over above with PAH and for which bosentan therapy is indicated according to national license Subjects with a mean pulmonary artery pressure of >25mmHg and a pulmonary artery wedge pressure of <15mmHg at rest via right heart catheterization within 3 years prior to randomization. Subjects whose baseline 6 Minute Walk Test distance is >100m and < 450m. Exclusion Criteria: PAH secondary to any aetiology including congenital heart disease other than those specified in the inclusion criteria Subjects whose 6 Minute Walk Test may be limited by conditions other than PAH related dyspnoea or fatigue eg. claudication from vascular insufficiency or arthritis.
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
West Los Angeles VA Healthcare, Pulmonary Hypertension Program
City
Los Angeles
State/Province
California
ZIP/Postal Code
90073
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Allegheny General Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15212
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
The Methodist Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Diagnostics Research Group
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
St. Vincents Hospital
City
Darlinghurst
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
The Prince Charles Hospital
City
Chermside
State/Province
Queensland
ZIP/Postal Code
4032
Country
Australia
Facility Name
Vseobecna fakultni nemocnice v Praze
City
Praha 2
ZIP/Postal Code
128 08
Country
Czechia
Facility Name
Institut klinicke a experimentalni mediciny, Klinika kardiologie
City
Praha 4
ZIP/Postal Code
140 21
Country
Czechia
Facility Name
Clinique des Maladies Respiratoires
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Hopital Claude Huriez
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Hopital Adules Brabois
City
Vandoeuvre Les Nancy
ZIP/Postal Code
54511
Country
France
Facility Name
Unfallkrankenhaus Berlin, Klinik fuer Innere Medizin
City
Berlin
ZIP/Postal Code
12683
Country
Germany
Facility Name
II. Medizinische Klinik, Kardiologie, Angiologie und Pneumologie
City
Coburg
ZIP/Postal Code
96450
Country
Germany
Facility Name
Universitaetsklinikum Essen, Zentrum fuer Innere Medizin, Klinik fuer Kardiologie
City
Essen
ZIP/Postal Code
45122
Country
Germany
Facility Name
Universitaetsklinikum Giessen und Marburg GmbH, Standort Giessen
City
Giessen
ZIP/Postal Code
35392
Country
Germany
Facility Name
Medizinische Hochschule Hannover
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Universitaetsklinikum des Saarlandes, Innere Medizin V
City
Homburg
ZIP/Postal Code
66421
Country
Germany
Facility Name
Medizinische Klinik und Poliklinik I, Universitaetsklinikum Leipzig
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Med. Klinik u. Poliklinik I der LMU Muenchen, Klinikum Grosshadern
City
Muenchen
ZIP/Postal Code
81377
Country
Germany
Facility Name
Praxis fuer Innere Medizin, Kardiologie und Angiologie
City
Nuernberg
ZIP/Postal Code
90402
Country
Germany
Facility Name
Missionsaerztliche Klinik Wuerzburg, Gemeinnuetzige Gesellschaft mbH
City
Wuerzburg
ZIP/Postal Code
97067
Country
Germany
Facility Name
Attikon Hospital
City
Haidari
State/Province
Athens
ZIP/Postal Code
12462
Country
Greece
Facility Name
Rambam Medical Center
City
Haifa
ZIP/Postal Code
31096
Country
Israel
Facility Name
Rabin Medical Centre
City
Petach Tikva
ZIP/Postal Code
49100
Country
Israel
Facility Name
Cardiologia, Azienda Ospedaliera Monaldi, Seconda Università di Napoli
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Unita' di Ipertensione Polmonare, Dipartimento di Scienze Respiratorie e Cardiovascolari
City
Roma
ZIP/Postal Code
00161
Country
Italy
Facility Name
Department of Surgery, National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
100
Country
Taiwan
Facility Name
PVDU
City
Papworth Everard
State/Province
Cambridgeshire
ZIP/Postal Code
CB23 3RE
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
28874133
Citation
Vizza CD, Jansa P, Teal S, Dombi T, Zhou D. Sildenafil dosed concomitantly with bosentan for adult pulmonary arterial hypertension in a randomized controlled trial. BMC Cardiovasc Disord. 2017 Sep 6;17(1):239. doi: 10.1186/s12872-017-0674-3.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A1481243&StudyName=Assess%20the%20Efficacy%20and%20Safety%20of%20Sildenafil%20When%20Added%20to%20Bosentan%20in%20the%20Treatment%20of%20Pulmonary%20Arterial%20Hypertension
Description
To obtain contact information for a study center near you, click here.

Learn more about this trial

Assess the Efficacy and Safety of Sildenafil When Added to Bosentan in the Treatment of Pulmonary Arterial Hypertension

We'll reach out to this number within 24 hrs