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: July 17, 2014
Last verified: July 2014
Results First Received: August 23, 2013  
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
Condition: Pulmonary Arterial Hypertension
Interventions: Drug: Bosentan
Drug: Sildenafil Citrate
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study was conducted at 29 active centers in 10 countries (10 centers in Germany, 5 centers in the United States of America [USA], 3 centers in France, 2 centers in Australia, Czech Republic, Italy, and Israel, and 1 center in Greece, Taiwan and United Kingdom [UK])

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were required to be on bosentan therapy at a stable dose for at least 3 months prior to enrolment. At baseline, the participants were randomized to receive sildenafil or placebo. Part A study consisted of 12 weeks double-blind phase and Part B study was open-label phase for 12 months.

Reporting Groups
  Description
Placebo

In Part A of the study: the participants received placebo three times a day (TID), in addition to their existing stable bosentan treatment (62.5 mg BID or 125 mg BID for minimum 3 months prior to randomization), for 12-Week Double-Blind Phase of the study.

In Part B of the study: All the participants received sildenafil 20 mg TID for 12 months.

Sildenafil

In Part A of the study: the participants received sildenafil 20 mg TID, in addition to their existing stable bosentan treatment (62.5 mg BID or 125 mg BID for minimum 3 months prior to randomization), for 12-Week Double-Blind Phase of the study.

In Part B of the study: All the participants received sildenafil 20 mg TID for 12 months.


Participant Flow:   Overall Study
    Placebo     Sildenafil  
STARTED     53     50  
COMPLETED     39 [1]   31 [2]
NOT COMPLETED     14     19  
[1] 48 participants completed double-blind phase
[2] 43 participants completed double-blind phase



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
Placebo

In Part A of the study: the participants received placebo three times a day (TID), in addition to their existing stable bosentan treatment (62.5 mg BID or 125 mg BID for minimum 3 months prior to randomization), for 12-Week Double-Blind Phase of the study.

In Part B of the study: All the participants received sildenafil 20 mg TID for 12 months

Sildenafil

In Part A of the study: the participants received sildenafil 20 mg TID, in addition to their existing stable bosentan treatment (62.5 mg BID or 125 mg BID for minimum 3 months prior to randomization), for 12-Week Double-Blind Phase of the study.

In Part B of the study: All the participants received sildenafil 20 mg TID for 12 months.

Total Total of all reporting groups

Baseline Measures
    Placebo     Sildenafil     Total  
Number of Participants  
[units: participants]
  53     50     103  
Age  
[units: Years]
Mean ± Standard Deviation
  56.9  ± 14.14     55.2  ± 15.10     56.0  ± 14.57  
Gender  
[units: Participants]
     
Female     41     37     78  
Male     12     13     25  
Six Minute Walk Test (6MWT) [1]
[units: Meters]
Mean ± Standard Deviation
  350.38  ± 87.587     354.44  ± 73.121     352.35  ± 80.520  
Mean Pulmonary Artery Pressure (mPAP)  
[units: Millimeter(mm)¬†of¬†mercury(Hg)]
Mean ± Standard Deviation
  44.9  ± 13.33     46.9  ± 12.47     45.8  ± 12.89  
World Health Organization Functional Class in Participants with Pulmonary Arterial Hypertension [2]
[units: Participants]
     
Class I     0     0     0  
Class II     15     20     35  
Class III     38     29     67  
Class IV     0     1     1  
[1] 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.
[2] Pulmonary Arterial Hypertension criteria for WHO Class: Class I (Participants with no limitation of physical activity); Class II (Participants with slight limitation of physical activity); Class III (Participants with marked limitation of physical activity); Class IV (Participants with inability to carry out any physical activity).



  Outcome Measures
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1.  Primary:   Change From Baseline in the Total Distance Walked During 6 Minute Walk Time (6MWT) at Week 12   [ Time Frame: Week 12 ]

2.  Secondary:   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 ]

3.  Secondary:   Clinical Worsening Events   [ Time Frame: Week 12 ]

4.  Secondary:   Change From Baseline in Borg Dyspnea Score at Week 12   [ Time Frame: Week 12 ]

5.  Secondary:   One Year Survival Probability From the Start of Sildenafil Treatment.   [ Time Frame: One year from the time of starting sildenafil ]

6.  Secondary:   One Year Survival From the Start of Sildenafil Treatment.   [ Time Frame: One year from the time of starting sildenafil ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com


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: July 17, 2014
Health Authority: United States: Food and Drug Administration