The Efficacy and Safety of Sildenafil Citrate Used in Combination With Intravenous Epoprostenol in PAH

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT00159861
First received: September 8, 2005
Last updated: December 20, 2013
Last verified: December 2013
Results First Received: April 2, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver);   Primary Purpose: Treatment
Condition: Pulmonary Hypertension
Intervention: Drug: Sildenafil citrate

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Subjects were entered into the open-label extension study portion upon completion of the preceding 16-week, placebo controlled core study portion or, for subjects who required a change in epoprostenol dose due to clinical deterioration, after at least 4 weeks in the core study portion.

Reporting Groups
  Description
Placebo: Core Study / Sildenafil: Extension Study Core Study: Placebo (16 weeks, or at least 4 weeks for subjects who required a change in epoprostenol dose due to clinical deterioration); Extension Study: Sildenafil (until last enrolled subject completed 3 years of treatment) - initial dose 20 mg TID (3 times daily), may have been increased to 40 mg TID or 80 mg TID at discretion of Investigator
Sildenafil: Core Study / Sildenafil: Extension Study Core Study (16 weeks, or at least 4 weeks for subjects who required a change in epoprostenol dose due to clinical deterioration): Sildenafil 20, 40, or 80 mg TID (3 times daily) based on toleration; Extension Study (until last enrolled subject completed 3 years of treatment): Sildenafil - initial dose 20 mg TID, may have been increased to 40 mg TID or 80 mg TID at discretion of Investigator

Participant Flow for 2 periods

Period 1:   Core Study - 16 Weeks
    Placebo: Core Study / Sildenafil: Extension Study     Sildenafil: Core Study / Sildenafil: Extension Study  
STARTED     133     134  
Treated     131     134  
COMPLETED     108 [1]   122 [2]
NOT COMPLETED     25     12  
Death                 3                 0  
Adverse Event                 12                 6  
Lack of Efficacy                 2                 3  
Reason Unspecified                 5                 3  
Subject Defaulted                 1                 0  
Randomized but not Treated                 2                 0  
[1] Entered A1481153: 115; Did not enter A1481153: 16
[2] Entered A1481153: 127; Did not enter A1481153: 7

Period 2:   Extension Study - up to 3 Years
    Placebo: Core Study / Sildenafil: Extension Study     Sildenafil: Core Study / Sildenafil: Extension Study  
STARTED     115 [1]   127 [1]
Treated     115     127  
COMPLETED     53     56  
NOT COMPLETED     62     71  
Death                 24                 28  
Adverse Event                 14                 14  
Lack of Efficacy                 5                 1  
Reason Unspecified                 12                 19  
Withdrawal by Subject                 7                 9  
[1] Subjects may have entered extension study after 4 weeks in core study (prior to completion).



  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.
No text entered.

Reporting Groups
  Description
Placebo/Sildenafil Core Study: Placebo; Extension Study: Sildenafil - initial dose 20 mg TID (3 times daily), may have been increased to 40 mg TID or 80 mg TID at discretion of Investigator
Sildenafil/Sildenafil Study A1481141: Sildenafil 20, 40, or 80 mg TID (3 times daily) based on toleration; Extension Study A1481153: Sildenafil - initial dose 20 mg TID, may have been increased to 40 mg TID or 80 mg TID at discretion of Investigator
Total Total of all reporting groups

Baseline Measures
    Placebo/Sildenafil     Sildenafil/Sildenafil     Total  
Number of Participants  
[units: participants]
  131     134     265  
Age, Customized  
[units: participants]
     
18 to 44 years     47     54     101  
45 to 64 years     73     64     137  
>= 65 years     11     16     27  
Gender  
[units: participants]
     
Female     102     110     212  
Male     29     24     53  



  Outcome Measures
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1.  Primary:   Categorized Change From Baseline in 6-Minute Walking Distance   [ Time Frame: 1 Year, 2 Year, 3 Year ]

2.  Secondary:   Survival Status   [ Time Frame: 1, 2, 3, 4, and 5 years ]

3.  Secondary:   Change in Pulmonary Hypertension Criteria for Functional Capacity and Therapeutic Class   [ Time Frame: 1 Year, 2 Year, 3 Year ]

4.  Secondary:   Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36)   [ Time Frame: Baseline, Month 15, Month 27, Month 39 ]

5.  Secondary:   Change From Baseline in European Quality of Life Scale (EuroQol) 5-Dimensions (EQ-5D): Utility Index Score   [ Time Frame: Baseline, Month 15, Month 27, Month 39 ]

6.  Secondary:   Change From Baseline in European Quality of Life (EuroQol) Visual Analogue Scale (EQ-5D VAS): Current Health State Score   [ Time Frame: Baseline, Month 15, Month 27, Month 39 ]

7.  Secondary:   Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36): Reported Health Transition Score   [ Time Frame: Baseline, Month 15, Month 27, Month 39 ]

8.  Secondary:   Change From Baseline in BORG Dyspnea Score   [ Time Frame: Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Month 9, Month 12, Month 15, Month 18, Month 21, Month 24, Month 27, Month 30, Month 33, Month 36 ]
  Hide Outcome Measure 8

Measure Type Secondary
Measure Title Change From Baseline in BORG Dyspnea Score
Measure Description BORG Dyspnea score: change from core study Baseline. Subject rating of maximum degree of dyspnea experienced at any time during the 6-Minute Walk Test. Range: 0 (no breathlessness at all) to 10 (maximum breathlessness).
Time Frame Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Month 9, Month 12, Month 15, Month 18, Month 21, Month 24, Month 27, Month 30, Month 33, Month 36  
Safety Issue No  

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.
FAS. N=number of subjects with evaluable data at core study Baseline; n=number of subjects with evaluable data at observation, Placebo, Sildenafil, respectively. Treatment groups shown by core study randomization; includes subjects who were only treated in the core study and those who continued into the extension study.

Reporting Groups
  Description
Placebo/Sildenafil Core Study A1481141: Placebo TID (3 times daily); Extension Study A1481153: Sildenafil - initial dose 20 mg TID (3 times daily), may have been increased to 40 mg TID or 80 mg TID at discretion of Investigator
Sldenafil/Sildenafil Core Study A1481141: Sildenafil 20, 40, or 80 mg TID (3 times daily) based on toleration; Extension Study A1481153: Sildenafil - initial dose 20 mg TID (3 times daily), may have been increased to 40 mg TID or 80 mg TID at discretion of Investigator

Measured Values
    Placebo/Sildenafil     Sldenafil/Sildenafil  
Number of Participants Analyzed  
[units: participants]
  115     123  
Change From Baseline in BORG Dyspnea Score  
[units: scoresĀ onĀ scale]
Median ( Full Range )
   
Week 4 (n=112, 120)     0.0  
  ( -9.0 to 10.0 )  
  0.0  
  ( -6.0 to 4.0 )  
Week 8 (n=106, 113)     0.0  
  ( -8.0 to 9.0 )  
  0.0  
  ( -6.0 to 4.0 )  
Week 12 (n=102, 108)     0.0  
  ( -6.0 to 4.0 )  
  0.0  
  ( -7.0 to 4.0 )  
Week 16 (n=95, 106)     0.0  
  ( -6.0 to 9.0 )  
  0.0  
  ( -7.0 to 6.0 )  
Week 20 (n=80, 96)     0.0  
  ( -8.0 to 6.0 )  
  0.0  
  ( -7.0 to 4.0 )  
Week 24 (n=91, 105)     0.0  
  ( -7.0 to 4.0 )  
  0.0  
  ( -8.0 to 4.0 )  
Month 9 (n=75, 98)     0.0  
  ( -4.0 to 4.0 )  
  0.0  
  ( -8.0 to 5.0 )  
Month 12 (n=72, 90)     0.0  
  ( -6.0 to 4.0 )  
  0.0  
  ( -7.0 to 4.0 )  
Month 15 (n=75, 91)     0.0  
  ( -6.0 to 3.0 )  
  0.0  
  ( -9.0 to 4.0 )  
Month 18 (n=67, 74)     0.0  
  ( -7.0 to 3.0 )  
  0.0  
  ( -8.0 to 4.0 )  
Month 21 (n=67, 79)     0.0  
  ( -6.0 to 3.0 )  
  0.0  
  ( -7.0 to 4.0 )  
Month 24 (n=68, 60)     0.0  
  ( -6.0 to 7.0 )  
  0.0  
  ( -7.0 to 5.0 )  
Month 27 (n=67, 69)     0.0  
  ( -4.0 to 4.0 )  
  0.0  
  ( -7.0 to 3.0 )  
Month 30 (n=55, 68)     0.0  
  ( -7.0 to 7.0 )  
  0.0  
  ( -8.0 to 5.0 )  
Month 33 (n=62, 65)     0.0  
  ( -4.0 to 7.0 )  
  0.0  
  ( -7.0 to 6.0 )  
Month 36 (n=51, 62)     0.0  
  ( -7.0 to 5.0 )  
  0.0  
  ( -7.0 to 5.0 )  

No statistical analysis provided for Change From Baseline in BORG Dyspnea Score



9.  Other Pre-specified:   Change in Epoprostenol Dose From Baseline Maintained for 6 Months   [ Time Frame: Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Month 9, and at 3-month intervals through Month 69 ]


  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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