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

Pulmonary Arterial Hypertension Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00323297
• Other study ID #: A1481243
• Secondary ID: 2006-001464-23PA
• Status: Completed
• Phase: Phase 4
• Start date: September 2006
• Est. completion date: August 2013

Study information

• Verified date: January 2021
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 105
• Est. completion date: August 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Bosentan
Bosentan + Placebo for 12 weeks of the study (double blind), then 12 months open label phase (bosentan + sildenafil)

Other:
• Placebo
Bosentan + Placebo for 12 weeks of the study (double blind), then 12 months open label phase (bosentan + sildenafil)

Drug:
• Bosentan
Bosentan + Sildenafil for 12 weeks of the study (double blind), then 12 months open label phase
• Sildenafil Citrate
Bosentan + Sildenafil for 12 weeks of the study (double blind), then 12 months open label phase

Locations

Country	Name	City	State
Australia	The Prince Charles Hospital	Chermside	Queensland
Australia	St. Vincents Hospital	Darlinghurst	New South Wales
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
Czechia	Institut klinicke a experimentalni mediciny, Klinika kardiologie	Praha 4
France	Clinique des Maladies Respiratoires	Lille
France	Hopital Claude Huriez	Lille
France	Hopital Adules Brabois	Vandoeuvre Les Nancy
Germany	Unfallkrankenhaus Berlin, Klinik fuer Innere Medizin	Berlin
Germany	II. Medizinische Klinik, Kardiologie, Angiologie und Pneumologie	Coburg
Germany	Universitaetsklinikum Essen, Zentrum fuer Innere Medizin, Klinik fuer Kardiologie	Essen
Germany	Universitaetsklinikum Giessen und Marburg GmbH, Standort Giessen	Giessen
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitaetsklinikum des Saarlandes, Innere Medizin V	Homburg
Germany	Medizinische Klinik und Poliklinik I, Universitaetsklinikum Leipzig	Leipzig
Germany	Med. Klinik u. Poliklinik I der LMU Muenchen, Klinikum Grosshadern	Muenchen
Germany	Praxis fuer Innere Medizin, Kardiologie und Angiologie	Nuernberg
Germany	Missionsaerztliche Klinik Wuerzburg, Gemeinnuetzige Gesellschaft mbH	Wuerzburg
Greece	Attikon Hospital	Haidari	Athens
Israel	Rambam Medical Center	Haifa
Israel	Rabin Medical Centre	Petach Tikva
Italy	Cardiologia, Azienda Ospedaliera Monaldi, Seconda Università di Napoli	Napoli
Italy	Unita' di Ipertensione Polmonare, Dipartimento di Scienze Respiratorie e Cardiovascolari	Roma
Taiwan	Department of Surgery, National Taiwan University Hospital	Taipei
United Kingdom	PVDU	Papworth Everard	Cambridgeshire
United States	Henry Ford Hospital	Detroit	Michigan
United States	Baylor College of Medicine	Houston	Texas
United States	The Methodist Hospital	Houston	Texas
United States	West Los Angeles VA Healthcare, Pulmonary Hypertension Program	Los Angeles	California
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Diagnostics Research Group	San Antonio	Texas

Sponsors (1)

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

Countries where clinical trial is conducted

United States,  Australia,  Czechia,  France,  Germany,  Greece,  Israel,  Italy,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Week 12
Secondary	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.	Week 12
Secondary	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.	Week 12
Secondary	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).	Week 12
Secondary	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 from the time of starting sildenafil
Secondary	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.	One year from the time of starting sildenafil

External Links

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