A Long Term Extension Study Evaluating Safety Of Sildenafil Citrate When Used To Treat Pulmonary Arterial Hypertension (PAH) In Children

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00159874
First received: September 8, 2005
Last updated: July 17, 2014
Last verified: July 2014
Results First Received: December 19, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Pulmonary Arterial 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
This extension study included 220 participants at 31 sites. 14 participants did not go from A1481131 (NCT00159913) to A1481156. Participants from one center in Canada participated in base study A1481131 (NCT00159913) but not in this extension study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants remained in the same dose group as in study A1481131 (NCT00159913). Participants randomized to placebo in NCT00159913 were rerandomized to sildenafil in A1481156. Placebo participants in low weight category were rerandomized to medium or high dose (1:2) and other weight categories were rerandomized to low, medium or high dose (1:1:1).

Reporting Groups
  Description
Sildenafil Low/Low Dose Participants randomized to sildenafil low dose in study A1481131 (NCT00159913) and in the extension study A1481156
Sildenafil Medium/ Medium Dose Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and in the extension study A1481156
Sildenafil High/ High Dose Participants randomized to sildenafil high dose in study A1481131 (NCT00159913) and in the extension study A1481156
Placebo/ Low Dose Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil low dose in study A1481156
Placebo/ Medium Dose Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in study A1481156
Placebo/ High Dose Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil high dose in study A1481156
Placebo Non-randomized This group comprised those placebo participants who either discontinued from base study A1481131 (NCT00159913) or chose not to enter study A1481156 and hence not randomly assigned to a sildenafil dose group at the start of study A1481156

Participant Flow:   Overall Study
    Sildenafil Low/Low Dose     Sildenafil Medium/ Medium Dose     Sildenafil High/ High Dose     Placebo/ Low Dose     Placebo/ Medium Dose     Placebo/ High Dose     Placebo Non-randomized  
STARTED     42     55     77     13     19     23     5  
Treated     42     55     77     13     19     23     5  
COMPLETED     22     25     34     7     11     11     0  
NOT COMPLETED     20     30     43     6     8     12     5  
Adverse Event                 2                 2                 5                 1                 1                 2                 0  
Does Not Meet Entrance Criteria                 1                 0                 1                 0                 0                 0                 0  
Lack of Efficacy                 2                 0                 1                 1                 0                 3                 0  
Lost to Follow-up                 1                 0                 3                 0                 1                 2                 1  
Not specified                 8                 8                 8                 0                 2                 1                 3  
Protocol Violation                 0                 5                 2                 0                 0                 0                 0  
Death                 3                 8                 15                 0                 1                 2                 0  
Withdrawal by Subject                 2                 6                 8                 4                 3                 2                 1  
Pregnancy                 1                 1                 0                 0                 0                 0                 0  



  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
Sildenafil Low/Low Dose Participants randomized to sildenafil low dose in study A1481131 (NCT00159913) and in the extension study A1481156
Sildenafil Medium/ Medium Dose Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and in the extension study A1481156
Sildenafil High/ High Dose Participants randomized to sildenafil high dose in study A1481131 (NCT00159913) and in the extension study A1481156
Placebo/ Low Dose Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil low dose in study A1481156
Placebo/ Medium Dose Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in study A1481156
Placebo/ High Dose Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil high dose in study A1481156
Placebo Non-randomized This group comprised those placebo participants who either discontinued from base study A1481131 (NCT00159913) or chose not to enter study A1481156 and hence not randomly assigned to a sildenafil dose group at the start of study A1481156
Total Total of all reporting groups

Baseline Measures
    Sildenafil Low/Low Dose     Sildenafil Medium/ Medium Dose     Sildenafil High/ High Dose     Placebo/ Low Dose     Placebo/ Medium Dose     Placebo/ High Dose     Placebo Non-randomized     Total  
Number of Participants  
[units: participants]
  42     55     77     13     19     23     5     234  
Age, Customized  
[units: Participants]
               
1-4     0     9     19     1     3     2     1     35  
5-12     25     28     36     11     10     14     2     126  
13-17     17     18     22     1     6     7     2     73  
>=18     0     0     0     0     0     0     0     0  
Gender  
[units: Participants]
               
Female     25     31     51     9     11     15     3     145  
Male     17     24     26     4     8     8     2     89  



  Outcome Measures
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1.  Primary:   Number of Participants Reporting at Least One Adverse Event   [ Time Frame: Up to Follow-Up visit (30 to 40 days after study completion or treatment discontinuation) ]

2.  Primary:   Number of Participants Reporting Treatment-related Adverse Events   [ Time Frame: Up to Follow-Up visit (30 to 40 days after study completion or treatment discontinuation) ]

3.  Primary:   Number of Participants Reporting at Least One Serious Adverse Event   [ Time Frame: Up to Follow-Up visit (30 to 40 days after study completion or treatment discontinuation) ]

4.  Primary:   Number of Participants Reporting Treatment-related Serious Adverse Events   [ Time Frame: Up to Follow-Up visit (30 to 40 days after study completion or treatment discontinuation) ]

5.  Primary:   Number of Deaths Reported in the Study Prior to the Data Monitoring Committee (DMC) Recommendation of Dose Down Titration   [ Time Frame: Pre-DMC Recommendation dose down titration (04 August 2011) ]

6.  Primary:   Number of Deaths Reported During This Study   [ Time Frame: Last follow-up visit or 30 days after the last administration of study drug ]

7.  Primary:   Discontinuation Due to Intolerability   [ Time Frame: Throughout the treatment duration (median treatment duration 1689 to 1744 days) ]

8.  Primary:   Downtitration in Dose Due to Intolerability.   [ Time Frame: Pre-DMC recomendation (04 August 2011) ]

9.  Primary:   Number of Participants With Deterioration Post Baseline in Visual Acuity Safety Tests   [ Time Frame: Week 36 ]

10.  Primary:   Number of Participants With Deterioration Post Baseline in Color Vision Monitoring Safety Tests.   [ Time Frame: Week 36 ]

11.  Primary:   Pediatric Cognitive Development Status at Week 16.   [ Time Frame: Week 16 ]

12.  Primary:   Pediatric Cognitive Development Status at Week 52.   [ Time Frame: Week 52 ]

13.  Primary:   Pediatric Motor Development Status at Week 16.   [ Time Frame: Week 16 ]

14.  Primary:   Pediatric Motor Development Status at Week 52   [ Time Frame: Week 52 ]

15.  Secondary:   Peak Volume of Oxygen (VO2) Consumed at Year 1 Using a Bicycle Ergometry Cardiopulmonary Exercise Test (CPX)   [ Time Frame: 1 year ]

16.  Secondary:   Percentage Change From Baseline in Percent Predicted Peak VO2 at Year 1.   [ Time Frame: Baseline, Year 1 ]

17.  Secondary:   Percent Change From Baseline in Time to Maximum VO2 at Year 1   [ Time Frame: Baseline, Year 1 ]

18.  Secondary:   Percent Change From Baseline in Respiratory Exchange Ratio at Year 1   [ Time Frame: Baseline, Year 1 ]

19.  Secondary:   Percent Change From Start of Sildenafil in Total Ventilation (VE) to Year 1   [ Time Frame: Year 1 ]

20.  Secondary:   Percentage Change From Baseline in End Tidal Oxygen (O2) at Year 1.   [ Time Frame: Baseline, Year 1 ]

21.  Secondary:   Percentage Change From Baseline in End Tidal Carbon Dioxide (CO2) at Year 1.   [ Time Frame: Baseline, Year 1 ]

22.  Secondary:   Percentage Change From Baseline in Anaerobic Threshold at Year 1.   [ Time Frame: Baseline, Year 1 ]

23.  Secondary:   Summary of Shift in Changes From Start of Sildenafil in World Health Organization Pulmonary Hypertension (WHO PH) Functional Class by A1481156 Treatment Group at Year 1.   [ Time Frame: Baseline, Year 1 ]

24.  Secondary:   Summary of Shift in Changes From Start of Sildenafil in WHO PH Functional Class by A1481156 Treatment Group at Year 2.   [ Time Frame: Baseline, Year 2 ]

25.  Secondary:   Summary of Shift in Changes From Start of Sildenafil in WHO PH Functional Class by A1481156 Treatment Group at Year 3.   [ Time Frame: Baseline, Year 3 ]

26.  Secondary:   Summary of Shift in Changes From Start of Sildenafil in WHO PH Functional Class by A1481156 Treatment Group at Year 4.   [ Time Frame: Baseline, Year 4 ]

27.  Secondary:   Additions From Baseline in Background Therapy up to the End of Study   [ Time Frame: Up to the end of study ]

28.  Secondary:   Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF28) as Assessed by the Psychosocial Scale at Year 1.   [ Time Frame: Baseline, Year 1 ]

29.  Secondary:   Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF28) as Assessed by the Physical Scale at Year 1.   [ Time Frame: Baseline, Year 1 ]

30.  Secondary:   Participant (Parent) Global Assessment at Year 1   [ Time Frame: Year 1 ]

31.  Secondary:   Physician Global Assessment at Year 1   [ Time Frame: Year 1 ]


  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 by Pfizer

Publications automatically indexed to this study:

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00159874     History of Changes
Other Study ID Numbers: A1481156
Study First Received: September 8, 2005
Results First Received: December 19, 2013
Last Updated: July 17, 2014
Health Authority: United States: Food and Drug Administration