Pulmonary Arterial HypertensionPhase 4NCT00323297
Assess the Efficacy and Safety of Sildenafil When Added to Bosentan in the Treatment of Pulmonary Arterial Hypertension
A Phase 4 study testing Bosentan and Sildenafil Citrate in people with Pulmonary Arterial Hypertension, run by Pfizer's Upjohn has merged with Mylan to form Viatris Inc. at 30 sites in 10 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Bosentan and Sildenafil Citrate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 105 participants
- Where
- 30 sitesin 10 countries
- Study dates
- Sep 2006to Aug 2013
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
30 sites in 10 countries.
30 sites in 10 countries
Germany10 sites
Unfallkrankenhaus Berlin, Klinik fuer Innere Medizin
Berlin, 12683
II. Medizinische Klinik, Kardiologie, Angiologie und Pneumologie
Coburg, 96450
Universitaetsklinikum Essen, Zentrum fuer Innere Medizin, Klinik fuer Kardiologie
Essen, 45122
Universitaetsklinikum Giessen und Marburg GmbH, Standort Giessen
Giessen, 35392
Medizinische Hochschule Hannover
Hanover, 30625
Universitaetsklinikum des Saarlandes, Innere Medizin V
Homburg, 66421
Medizinische Klinik und Poliklinik I, Universitaetsklinikum Leipzig
Leipzig, 04103
Med. Klinik u. Poliklinik I der LMU Muenchen, Klinikum Grosshadern
München, 81377
Praxis fuer Innere Medizin, Kardiologie und Angiologie
Nuremberg, 90402
Missionsaerztliche Klinik Wuerzburg, Gemeinnuetzige Gesellschaft mbH
Würzburg, 97067
United States6 sites
Henry Ford Hospital
Detroit, Michigan, 48202
Baylor College of Medicine
Houston, Texas, 77030
The Methodist Hospital
Houston, Texas, 77030
West Los Angeles VA Healthcare, Pulmonary Hypertension Program
Los Angeles, California, 90073
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
Diagnostics Research Group
San Antonio, Texas, 78229
France3 sites
Clinique des Maladies Respiratoires
Lille, 59037
Hopital Claude Huriez
Lille, 59037
Hopital Adules Brabois
Vandœuvre-lès-Nancy, 54511
Australia2 sites
The Prince Charles Hospital
Chermside, Queensland, 4032
St. Vincents Hospital
Darlinghurst, New South Wales, 2010
Czechia2 sites
Vseobecna fakultni nemocnice v Praze
Prague, 128 08
Institut klinicke a experimentalni mediciny, Klinika kardiologie
Prague, 140 21
Israel2 sites
Rambam Medical Center
Haifa, 31096
Rabin Medical Centre
Petah Tikva, 49100
Italy2 sites
Cardiologia, Azienda Ospedaliera Monaldi, Seconda Università di Napoli
Naples, 80131
Unita' di Ipertensione Polmonare, Dipartimento di Scienze Respiratorie e Cardiovascolari
Roma, 00161
Taiwan1 site
Department of Surgery, National Taiwan University Hospital
Taipei, 100
About this study
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)
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.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- Bosentan, Placebo, Sildenafil Citrate
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BosentanDrug
Bosentan + Placebo for 12 weeks of the study (double blind), then 12 months open label phase (bosentan + sildenafil)
PlaceboOther
Bosentan + Placebo for 12 weeks of the study (double blind), then 12 months open label phase (bosentan + sildenafil)
BosentanDrug
Bosentan + Sildenafil for 12 weeks of the study (double blind), then 12 months open label phase
Sildenafil CitrateDrug
Bosentan + Sildenafil for 12 weeks of the study (double blind), then 12 months open label phase
| Study group | Role | What they receive |
|---|---|---|
| placebo | Placebo comparator | Not described Receives: Drug: Bosentan; Other: Placebo |
| Active | Experimental | Not described Receives: Drug: Bosentan; Drug: Sildenafil Citrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 12
Secondary outcomes (5)
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.
Measured: Week 12
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.
Measured: Week 12
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).
Measured: Week 12
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.
Measured: One year from the time of starting 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.
Measured: One year from the time of starting sildenafil
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2006 (estimated)
- Study startSep 2006
- Primary completionAug 2013
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00323297
- Sponsor's protocol ID
- A1481243
- Other IDs
- 2006-001464-23, PATHWAYS
- Status last verified
- Jan 2021
- First submitted
- 5 May 2006
- Last updated
- 1 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 28874133
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00323297
- Acronym / sponsor ID
- A1481243
- Conditions
- Pulmonary Arterial Hypertension
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 105 participants (actual)
- Lead sponsor
- Pfizer's Upjohn has merged with Mylan to form Viatris Inc.Industry (pharma, biotech, devices)
- Study start
- Sep 2006
- Primary completion
- Aug 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 9 May 2006 (estimated)
- Results
- Posted 19 Nov 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| placebo | Placebo comparator | Drug: Bosentan, Other: Placebo |
| Active | Experimental | Drug: Bosentan, Drug: Sildenafil Citrate |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BosentanBosentan + Placebo for 12 weeks of the study (double blind), then 12 months open label phase (bosentan + sildenafil) | Drug | placebo |
| PlaceboBosentan + Placebo for 12 weeks of the study (double blind), then 12 months open label phase (bosentan + sildenafil) | Other | placebo |
| BosentanBosentan + Sildenafil for 12 weeks of the study (double blind), then 12 months open label phase | Drug | Active |
| Sildenafil CitrateBosentan + Sildenafil for 12 weeks of the study (double blind), then 12 months open label phase | Drug | Active |
Primary outcome
Change From Baseline in the Total Distance Walked During 6 Minute Walk Time (6MWT) at Week 12
Time frame: 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.
5 secondary outcomes
Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Class in Participants With PAH at Week 12 LOCF
Time frame: Week 12
Clinical Worsening Events
Time frame: Week 12
Change From Baseline in Borg Dyspnea Score at Week 12
Time frame: Week 12
One Year Survival Probability From the Start of Sildenafil Treatment.
Time frame: One year from the time of starting sildenafil
One Year Survival From the Start of Sildenafil Treatment.
Time frame: One year from the time of starting sildenafil
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28874133Vizza 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
30 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Bosentan and Sildenafil Citrate in people with Pulmonary Arterial Hypertension, run by Pfizer's Upjohn has merged with Mylan to form Viatris Inc. at 30 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in Germany, United States, France, Australia, Czechia and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in the Total Distance Walked During 6 Minute Walk Time (6MWT) at Week 12 (time frame: Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00323297, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2021.