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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00323297
First received: May 5, 2006
Last updated: January 8, 2014
Last verified: January 2014
  Purpose

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).



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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00323297

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

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00323297     History of Changes
Other Study ID Numbers: A1481243
Study First Received: May 5, 2006
Results First Received: August 23, 2013
Last Updated: January 8, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hypertension, Pulmonary
Hypertension
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases
Bosentan
Sildenafil
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014