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

This study has been completed.
Information provided by (Responsible Party):
Pfizer Identifier:
First received: May 5, 2006
Last updated: July 17, 2014
Last verified: July 2014

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.

Condition Intervention Phase
Pulmonary Arterial Hypertension
Drug: Bosentan
Drug: Sildenafil Citrate
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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).

Resource links provided by NLM:

Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Change From Baseline in the Total Distance Walked During 6 Minute Walk Time (6MWT) at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

    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]);

    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).

  • One Year Survival Probability From the Start of Sildenafil Treatment. [ Time Frame: One year from the time of starting sildenafil ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: One year from the time of starting sildenafil ] [ Designated as safety issue: Yes ]
    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.

Enrollment: 104
Study Start Date: September 2006
Study Completion Date: August 2013
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: placebo Drug: Bosentan
Bosentan + Placebo for 12 weeks of the study (double blind), then 12 months open label phase (bosentan + sildenafil)
Drug: Placebo
Placebo for 12 weeks of the study (double blind), then 12 months open label phase (bosentan + sildenafil)
Experimental: Active Drug: Sildenafil Citrate
Bosentan + Sildenafil for 12 weeks of the study (double blind), then 12 months open label phase


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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.
  Contacts and Locations
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Please refer to this study by its identifier: NCT00323297

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United States, California
Pfizer Investigational Site
Los Angeles, California, United States, 90073
United States, Michigan
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Detroit, Michigan, United States, 48202
United States, Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15212
United States, Texas
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Houston, Texas, United States, 77030
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San Antonio, Texas, United States, 78229
Australia, New South Wales
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Darlinghurst, New South Wales, Australia, 2010
Australia, Queensland
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Chermside, Queensland, Australia, 4032
Czech Republic
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Praha 2, Czech Republic, 128 08
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Praha 4, Czech Republic, 140 21
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Lille, France, 59037
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Vandoeuvre Les Nancy, France, 54511
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Berlin, Germany, 12683
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Coburg, Germany, 96450
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Essen, Germany, 45122
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Giessen, Germany, 35392
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Hannover, Germany, 30625
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Homburg, Germany, 66421
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Leipzig, Germany, 04103
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Muenchen, Germany, 81377
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Nuernberg, Germany, 90402
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Wuerzburg, Germany, 97067
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Haidari, Athens, Greece, 12462
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Haifa, Israel, 31096
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Petach Tikva, Israel, 49100
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Napoli, Italy, 80131
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Roma, Italy, 00161
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Taipei, Taiwan, 100
United Kingdom
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Papworth Everard, Cambridgeshire, United Kingdom, CB23 3RE
Sponsors and Collaborators
Study Director: Pfizer Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer Identifier: NCT00323297     History of Changes
Other Study ID Numbers: A1481243
Study First Received: May 5, 2006
Results First Received: August 23, 2013
Last Updated: July 17, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents
Antihypertensive Agents processed this record on October 19, 2014