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

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ClinicalTrials.gov Identifier: NCT00323297
Recruitment Status : Completed
First Posted : May 9, 2006
Results First Posted : November 19, 2013
Last Update Posted : February 1, 2021
Sponsor:
Information provided by (Responsible Party):
Pfizer ( Pfizer's Upjohn has merged with Mylan to form Viatris Inc. )

Tracking Information
First Submitted Date  ICMJE May 5, 2006
First Posted Date  ICMJE May 9, 2006
Results First Submitted Date  ICMJE August 23, 2013
Results First Posted Date  ICMJE November 19, 2013
Last Update Posted Date February 1, 2021
Study Start Date  ICMJE September 2006
Actual Primary Completion Date August 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 18, 2013)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 5, 2006)
To assess the effect on exercise capacity (as measured by the 6 Minute Walk Test) after 12 weeks of treatment of sildenafil (20mg TID) or placebo, when added to subjects with PAH who are stabilized on bosentan therapy
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 17, 2014)
  • 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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 5, 2006)
  • To assess the safety and tolerability of sildenafil (20mg TID) or placebo, when added to subjects with PAH who are currently treated with bosentan, after 12 weeks of treatment.
  • To assess the safety and tolerability of the open label treatment of sildenafil (20mg TID) and bosentan therapy in subjects with PAH after 12 months of treatment.
  • To assess the effect on other clinical outcome measures (clinical worsening, Borg dyspnoea score and PAH functional class) after 12 weeks of treatment of sildenafil (20mg TID) or placebo when added to bosentan therapy in subjects with PAH.
  • To determine the population pharmacokinetic parameters of sildenafil and bosentan.
  • To investigate the Pharmacokinetic/Pharmacodynamic (PK/PD) relationship between sildenafil and bosentan exposure on the 6-Minute Walk Test.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Assess the Efficacy and Safety of Sildenafil When Added to Bosentan in the Treatment of Pulmonary Arterial Hypertension
Official Title  ICMJE 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)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Pulmonary Arterial Hypertension
Intervention  ICMJE
  • 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
  • Drug: Sildenafil Citrate
    Bosentan + Sildenafil for 12 weeks of the study (double blind), then 12 months open label phase
Study Arms  ICMJE
  • Placebo Comparator: placebo
    Interventions:
    • Drug: Bosentan
    • Other: Placebo
  • Experimental: Active
    Interventions:
    • Drug: Bosentan
    • Drug: Sildenafil Citrate
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 27, 2014)
105
Original Enrollment  ICMJE
 (submitted: May 5, 2006)
106
Actual Study Completion Date  ICMJE August 2013
Actual Primary Completion Date August 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Czechia,   France,   Germany,   Greece,   Israel,   Italy,   Taiwan,   United Kingdom,   United States
Removed Location Countries Belgium,   Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT00323297
Other Study ID Numbers  ICMJE A1481243
2006-001464-23 ( EudraCT Number )
PATHWAYS ( Other Identifier: Alias Study Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer ( Pfizer's Upjohn has merged with Mylan to form Viatris Inc. )
Study Sponsor  ICMJE Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP