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

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00159874
• Collaborator: (none)
• Enrollment: 234
• Locations: 39
• Arms: 3
• Duration (Months): 107
• Patients Per Site: 6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Active treatment, dose-blinded extension study evaluating the safety and long term efficacy of sildenafil citrate in children with PAH.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Arterial Hypertension	Drug: Sildenafil citrate; Drug: Sildenafil citrate; Drug: Sildenafil citrate	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 234 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Long-Term Extension Study to Assess Safety of Oral Sildenafil Citrate In The Treatment Of Subjects Who Have Completed Study A1481131
• Study Start Date: Jan 1, 2004
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sildenafil high dose As per Protocol Amendment 8 (Aug 2011), all doses in the high dose treatment group were discontinued. Subjects who were receiving these doses and continued in the study were requested to down titrate.	Drug: Sildenafil citrate; Oral, subjects with body weight ≥8 - 20 kg: 20 mg 3 times a day (tid) subjects with body weight >20 - 45 kg: 40 mg 3 times a day (tid) subjects with body weight >45 kg: 80 mg 3 times a day (tid)
Experimental: Sildenafil Low dose	Drug: Sildenafil citrate; Oral,10 mg 3 times a day (tid), only subjects with body weight >20 kg
Experimental: Sildenafil medium dose As per Protocol Amendment 8 (August 2011), the dose 40 mg TID in the medium dose treatment group was discontinued. Subjects who were receiving this dose and continued in the study were requested to down titrate.	Drug: Sildenafil citrate; Oral, subjects with body weight ≥8 - 20 kg: 10 mg 3 times a day (tid); subjects with body weight >20 - 45 kg: 20 mg 3 times a day (tid); subjects with body weight >45 kg: 40 mg 3 times a day (tid)

Outcome Measures

Primary Outcome Measures

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

   Safety was measured according to standard adverse event collection as described in the adverse event section of the results. Complete tables of the adverse events according to the A1481156 treatment groups are provided in the reported adverse event section.

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

   Safety was measured according to standard adverse event collection as described in the adverse event section of the results.

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

   Safety was measured according to standard adverse event collection as described in the adverse event section of the results. Complete tables of the serious adverse events according to the A1481156 treatment groups are provided in the reported adverse event section.

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

   All serious adverse events regardless of treatment group or suspected relationship to study drug were reported. Investigators were to provide independent determination of possible causality of any serious adverse event.

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

   Deaths were reported immediately independent of the circumstances or suspected cause at any time during the study through the last follow-up visit or 30 days after the last administration of study drug, whichever comes later.

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

   Deaths were reported immediately independent of the circumstances or suspected cause at any time during the study through the last follow-up visit or 30 days after the last administration of study drug, whichever comes later.

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

   Participant who experienced drug-related intolerance, the participant's dose was reduced by 50%. If, after a dose reduction, the participant continued to appear intolerant, they were discontinued from study treatment.

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

   Based on review of the survival data, DMC concluded that the high dose of sildenafil was associated with a harmful effect on survival when compared to the low dose. The DMC also expressed concern as to the potential dose-response relationship between increasing dose and mortality. Therefore, on 04 August 2011, the DMC recommended discontinuation of the 40 mg and 80 mg three times a day (TID) doses, as well as the 20 mg TID dose in children with body weight ≤20 kg. The protocol was amended per DMC recommendations.

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

   Visual Acuity is measured either using the reduced Snellen test or via Teller cards, and was assessed in the left and right eyes separately. There were 9 lines on the reduced Snellen chart which were coded as 6/60, 6/36, 6/24, 6/18, 6/12, 6/9, 6/6, 6/5, 6/4 (where 6/60 was the easiest to read and 6/4 was the most difficult to read). If a participant experienced a visual adverse event the investigator was asked to perform additional ocular assessments either at the visit when the participant reported the visual adverse event or at an unplanned visit.

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

    Colour vision was measured where appropriate via the Farnsworth-Munsell D-15 Hue test. This test was performed in both eyes simultaneously or just in a single specific eye. If using a single eye the same eye was used throughout the study. In case of young participants an age-and-ability-appropriate evaluation such as the Ishihara Test for Unlettered Persons were conducted.

11. Pediatric Cognitive Development Status at Week 16. [Week 16]

    Participant's cognitive development status was assessed at A1481156 baseline (Week 16 in A1481131; NCT00159913) using the physician assessment questions. Assessment question (i.e., compared to other children the participant's age group is this participant's cognitive development limited?) included the following criteria : severely limited, moderately limited, mildly limited and not limited.

12. Pediatric Cognitive Development Status at Week 52. [Week 52]

    Participant's cognitive development status was assessed at Week 52 using the physician assessment questions. Assessment question (i.e., compared to other children the participant's age group is this participant's cognitive development limited?) included the following criteria : severely limited, moderately limited, mildly limited and not limited.

13. Pediatric Motor Development Status at Week 16. [Week 16]

    Participant's motor development status was assessed at A1481156 baseline (Week 16 in A1481131; NCT00159913) using the physician assessment questions. Assessment question (i.e., compared to other children the participant's age group is this participant's motor development limited?) included the following criteria : severely limited, moderately limited, mildly limited and not limited.

14. Pediatric Motor Development Status at Week 52 [Week 52]

    Participant's motor development status was assessed at Week 52 using the physician assessment questions. Assessment question (i.e., compared to other children the participant's age group is this participant's motor development limited?) included the following criteria : severely limited, moderately limited, mildly limited and not limited.

Secondary Outcome Measures

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

   Exercise Tolerance Test (CPX test) was performed on developmentally able participants to determine the peak volume of VO2 consumed. Participants were assumed to be developmentally able if they had a CPX exercise assessment at any visit during study A1481131 (NCT00159913). The CPX tests were performed as close to trough plasma levels of sildenafil as possible, i.e., prior to dosing and at least 4 hours after the previous dose. If participants were able to perform the CPX test in Study A1481131 (NCT00159913), they were expected to be able to perform the exercise paradigm in the extension study (A1481156) unless their clinical condition had deteriorated and the investigator considered this was unsafe for the participant

2. Percentage Change From Baseline in Percent Predicted Peak VO2 at Year 1. [Baseline, Year 1]

   Exercise Tolerance Test (CPX test) was performed on developmentally able participants to measure the percent predicted peak VO2 at Week 16 and Year 1. Participants were assumed to be developmentally able if they had a CPX exercise assessment at any visit during study A1481131 (NCT00159913). The CPX tests were performed as close to trough plasma levels of sildenafil as possible, i.e., prior to dosing and at least 4 hours after the previous dose. If participants were able to perform the CPX test in Study A1481131 (NCT00159913), they were expected to be able to perform the exercise paradigm in the extension study (A1481156) unless their clinical condition had deteriorated and the investigator considered this was unsafe for the participant.

3. Percent Change From Baseline in Time to Maximum VO2 at Year 1 [Baseline, Year 1]

   Exercise Tolerance Test (CPX test) was performed on developmentally able participants to determine the time to maximum VO2. Participants were assumed to be developmentally able if they had a CPX exercise assessment at any visit during study A1481131 (NCT00159913). The CPX tests were performed as close to trough plasma levels of sildenafil as possible, i.e., prior to dosing and at least 4 hours after the previous dose. If participants were able to perform the CPX test in Study A1481131 (NCT00159913), they were expected to be able to perform the exercise paradigm in the extension study (A1481156) unless their clinical condition had deteriorated and the investigator considered this was unsafe for the participant.

4. Percent Change From Baseline in Respiratory Exchange Ratio at Year 1 [Baseline, Year 1]

   This is the ratio of carbon dioxide (CO2) produced to O2 consumed [VCO2/VO2]. Exercise Tolerance Test was performed on developmentally able participants to determine the respiratory exchange ratio on week 16 and Year 1. Participants were assumed to be developmentally able if they had a CPX exercise assessment at any visit during study A1481131 (NCT00159913).

5. Percent Change From Start of Sildenafil in Total Ventilation (VE) to Year 1 [Year 1]

   Exercise Tolerance Test (CPX test) was performed on developmentally able participants to determine the total ventilation. Participants were assumed to be developmentally able if they had a CPX exercise assessment at any visit during study A1481131 (NCT00159913). The CPX tests were performed as close to trough plasma levels of sildenafil as possible, i.e., prior to dosing and at least 4 hours after the previous dose. If participants were able to perform the CPX test in Study A1481131 (NCT00159913), they were expected to be able to perform the exercise paradigm in the extension study (A1481156) unless their clinical condition had deteriorated and the investigator considered this was unsafe for the participant.

6. Percentage Change From Baseline in End Tidal Oxygen (O2) at Year 1. [Baseline, Year 1]

   Exercise Tolerance Test (CPX test) was performed on developmentally able participants to measure the End Tidal O2 at Year 1. Participants were assumed to be developmentally able if they had a CPX exercise assessment at any visit during study A1481131 (NCT00159913). The CPX tests were performed as close to trough plasma levels of sildenafil as possible, i.e., prior to dosing and at least 4 hours after the previous dose. If participants were able to perform the CPX test in Study A1481131 (NCT00159913), they were expected to be able to perform the exercise paradigm in the extension study (A1481156) unless their clinical condition had deteriorated and the investigator considered this was unsafe for the participant.

7. Percentage Change From Baseline in End Tidal Carbon Dioxide (CO2) at Year 1. [Baseline, Year 1]

   Exercise Tolerance Test (CPX test) was performed on developmentally able participants to measure the End Tidal CO2 at Year 1. Participants were assumed to be developmentally able if they had a CPX exercise assessment at any visit during study A1481131 (NCT00159913). The CPX tests were performed as close to trough plasma levels of sildenafil as possible, i.e., prior to dosing and at least 4 hours after the previous dose. If participants were able to perform the CPX test in Study A1481131 (NCT00159913), they were expected to be able to perform the exercise paradigm in the extension study (A1481156) unless their clinical condition had deteriorated and the investigator considered this was unsafe for the participant.

8. Percentage Change From Baseline in Anaerobic Threshold at Year 1. [Baseline, Year 1]

   Exercise Tolerance Test (CPX test) was performed on developmentally able participants to measure the anaerobic threshold at Week 16 and Year 1. Participants were assumed to be developmentally able if they had a CPX exercise assessment at any visit during study A1481131 (NCT00159913). The CPX tests were performed as close to trough plasma levels of sildenafil as possible, i.e., prior to dosing and at least 4 hours after the previous dose. If participants were able to perform the CPX test in Study A1481131 (NCT00159913), they were expected to be able to perform the exercise paradigm in the extension study (A1481156) unless their clinical condition had deteriorated and the investigator considered this was unsafe for the participant.

9. 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. [Baseline, Year 1]

   The WHO PH functional classification was as follows: Class I : Participants with PH but without resulting limitation of physical activity. Class II : Participants with PH resulting in slight limitation of physical activity. Class III : Participants with PH resulting in marked limitation of physical activity. Class IV : Participants with PH with inability to carry out any physical activity without symptoms. Changes from baseline in functional class were summarized at Years 1, 2, 3, and 4. Numbers of participants improving by 3 classes, improving by 2 classes, improving by 1 class, not changing, worsening by 1 class, worsening by 2 classes or worsening by 3 classes from A1481131 baseline at Years 1, 2, 3 and 4 were evaluated.

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

    The WHO PH functional classification was as follows: Class I : Participants with PH but without resulting limitation of physical activity. Class II : Participants with PH resulting in slight limitation of physical activity. Class III : Participants with PH resulting in marked limitation of physical activity. Class IV : Participants with PH with inability to carry out any physical activity without symptoms. Changes from baseline in functional class were summarised at Years 1, 2, 3, and 4. Numbers of participants improving by 3 classes, improving by 2 classes, improving by 1 class, not changing, worsening by 1 class, worsening by 2 classes or worsening by 3 classes from A1481131 baseline at Years 1, 2, 3 and 4 were evaluated.

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

    The WHO PH functional classification was as follows: Class I : Participants with PH but without resulting limitation of physical activity. Class II : Participants with PH resulting in slight limitation of physical activity. Class III : Participants with PH resulting in marked limitation of physical activity. Class IV : Participants with PH with inability to carry out any physical activity without symptoms. Changes from baseline in functional class were summarised at Years 1, 2, 3, and 4. Numbers of participants improving by 3 classes, improving by 2 classes, improving by 1 class, not changing, worsening by 1 class, worsening by 2 classes or worsening by 3 classes from A1481131 (NCT00159913) baseline at Years 1, 2, 3 and 4 were evaluated.

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

    The WHO PH functional classification was as follows: Class I : Participants with PH but without resulting limitation of physical activity. Class II : Participants with PH resulting in slight limitation of physical activity. Class III : Participants with PH resulting in marked limitation of physical activity. Class IV : Participants with PH with inability to carry out any physical activity without symptoms. Changes from baseline in functional class were summarised at Years 1, 2, 3, and 4. Numbers of participants improving by 3 classes, improving by 2 classes, improving by 1 class, not changing, worsening by 1 class, worsening by 2 classes or worsening by 3 classes from A1481131 baseline at Years 1, 2, 3 and 4 were evaluated.

13. Additions From Baseline in Background Therapy up to the End of Study [Up to the end of study]

    This was defined as an addition or discontinuation in the class(es) of drugs used as background medication (e.g., anticoagulants, oxygen, diuretics, calcium channel blockers, and digoxin) compared to baseline of Study A1481131 (NCT00159913).

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

    CHQ: 50-item, 15 subscale parent or legal guardian assessed instrument of child's physical, emotional, social well-being, and relative burden of disease on the parents; rated on Likert-type scale: range 0 to 100; higher scores indicate a more positive health status. Global indicators for Physical Health and Psychosocial Health are weighted composites derived from subscale items using scoring algorithms (transformed scores); range 0 to 100: higher scores indicate more positive health status.

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

    CHQ: 50-item, 15 subscale parent or legal guardian assessed instrument of child's physical, emotional, social well-being, and relative burden of disease on the parents; rated on Likert-type scale: range 0 to 100; higher scores indicate a more positive health status. Global indicators for Physical Health and Psychosocial Health are weighted composites derived from subscale items using scoring algorithms (transformed scores); range 0 to 100: higher scores indicate more positive health status.

16. Participant (Parent) Global Assessment at Year 1 [Year 1]

    The participant (parent) global assessment of disease severity was assessed at Year 1 in this extension study. The number and percentage of participants markedly improved, moderately improved, mild improvement, no change, slightly worse, moderately worse, markedly worse were evaluated. Participants who withdrew from study treatment after at least 10 weeks of treatment were requested to perform the global assessments.

17. Physician Global Assessment at Year 1 [Year 1]

    The physician global assessment of disease severity was assessed at Year 1 in this extension study. The number and percentage of participants with markedly improved, moderately improved, mild improvement, no change, slightly worse, moderately worse, markedly worse were evaluated. Participants who withdrew from study treatment after at least 10 weeks of treatment were requested to perform the global assessments.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must complete the 16 Week double-blind efficacy study A1481131.

Exclusion Criteria:

• Any patient who did not complete Study A1481131.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Palo Alto	California	United States	34304
2	Pfizer Investigational Site	Palo Alto	California	United States	94305
3	Pfizer Investigational Site	Stanford	California	United States	94305
4	Pfizer Investigational Site	Aurora	Colorado	United States	80045
5	Pfizer Investigational Site	Boston	Massachusetts	United States	02115
6	Pfizer Investigational Site	Ann Arbor	Michigan	United States	48109
7	Pfizer Investigational Site	Saint Louis	Missouri	United States	63110
8	Pfizer Investigational Site	New York	New York	United States	10032
9	Pfizer Investigational Site	Columbus	Ohio	United States	43205
10	Pfizer Investigational Site	Charleston	South Carolina	United States	29425
11	Pfizer Investigational Site	Seattle	Washington	United States	98105
12	Pfizer Investigational Site	Sao Paulo	SP	Brazil	04012-909
13	Pfizer Investigational Site	São Paulo	SP	Brazil	04023-062
14	Pfizer Investigational Site	Puente Alto	Santiago	Chile
15	Pfizer Investigational Site	Medellin	Antioquia	Colombia
16	Pfizer Investigational Site	Bogota	Cundinamarca	Colombia
17	Pfizer Investigational Site	Guatemala		Guatemala
18	Pfizer Investigational Site	Budapest		Hungary	1083
19	Pfizer Investigational Site	Budapest		Hungary	1096
20	Pfizer Investigational Site	Szeged		Hungary	6720
21	Pfizer Investigational Site	Hyderabad	Andhra Pradesh	India	500 001
22	Pfizer Investigational Site	Hyderabad	Andhra Pradesh	India	500 073
23	Pfizer Investigational Site	Kochi	Kerala	India	682 041
24	Pfizer Investigational Site	Bologna		Italy	40138
25	Pfizer Investigational Site	Tokyo		Japan
26	Pfizer Investigational Site	Penang		Malaysia	10050
27	Pfizer Investigational Site	Penang		Malaysia	10900
28	Pfizer Investigational Site	Penang		Malaysia	11600
29	Pfizer Investigational Site	Mexico	DF	Mexico	14080
30	Pfizer Investigational Site	Krakow		Poland	30-663
31	Pfizer Investigational Site	Ruda Slaska		Poland	41-703
32	Pfizer Investigational Site	Warszawa		Poland	04-730
33	Pfizer Investigational Site	Zabrze		Poland	41-800
34	Pfizer Investigational Site	Moscow		Russian Federation	115478
35	Pfizer Investigational Site	Moscow		Russian Federation	125412
36	Pfizer Investigational Site	Lund		Sweden	221 85
37	Pfizer Investigational Site	Kaohsiung		Taiwan	81346
38	Pfizer Investigational Site	Taipei		Taiwan	100
39	Pfizer Investigational Site	Taipei		Taiwan	11217

Sponsors and Collaborators

• Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• ClinicalTrials.gov Identifier: NCT00159874
• Other Study ID Numbers: A1481156
• First Posted: Sep 12, 2005
• Last Update Posted: Feb 1, 2021
• Last Verified: Jan 1, 2021

• Keywords provided by Pfizer's Upjohn has merged with Mylan to form Viatris Inc.: children
• Additional relevant MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension; Sildenafil Citrate; Citric Acid; Sodium Citrate

Study Results

Participant Flow

Recruitment Details	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 Detail	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).

Arm/Group Title	Sildenafil Low/Low Dose	Sildenafil Medium/ Medium Dose	Sildenafil High/ High Dose	Placebo/ Low Dose	Placebo/ Medium Dose	Placebo/ High Dose	Placebo Non-randomized
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil low dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil high dose in study A1481156	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
Period Title: Overall Study
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

Baseline Characteristics

Arm/Group Title	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
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil low dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil high dose in study A1481156	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 of all reporting groups
Overall Participants	42	55	77	13	19	23	5	234
Age, Customized (Number) [Number]
1-4	0 0%	9 16.4%	19 24.7%	1 7.7%	3 15.8%	2 8.7%	1 20%	35 15%
5-12	25 59.5%	28 50.9%	36 46.8%	11 84.6%	10 52.6%	14 60.9%	2 40%	126 53.8%
13-17	17 40.5%	18 32.7%	22 28.6%	1 7.7%	6 31.6%	7 30.4%	2 40%	73 31.2%
>=18	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	25 59.5%	31 56.4%	51 66.2%	9 69.2%	11 57.9%	15 65.2%	3 60%	145 62%
Male	17 40.5%	24 43.6%	26 33.8%	4 30.8%	8 42.1%	8 34.8%	2 40%	89 38%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Reporting at Least One Adverse Event
Description	Safety was measured according to standard adverse event collection as described in the adverse event section of the results. Complete tables of the adverse events according to the A1481156 treatment groups are provided in the reported adverse event section.
Time Frame	Up to Follow-Up visit (30 to 40 days after study completion or treatment discontinuation)

Outcome Measure Data

Analysis Population Description

The safety population consisted of all participants who had taken at least one dose of study medication in A1481131 (NCT00159913).

Arm/Group Title	Sildenafil Low/Low Dose	Sildenafil Medium/ Medium Dose	Sildenafil High/ High Dose	Placebo/ Low Dose	Placebo/ Medium Dose	Placebo/ High Dose	Placebo Non-randomized
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil low dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil high dose in study A1481156	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
Measure Participants	42	55	77	13	19	23	5
Number [Participants]	41 97.6%	55 100%	73 94.8%	13 100%	19 100%	22 95.7%	3 60%

2. Primary Outcome

Title	Number of Participants Reporting Treatment-related Adverse Events
Description	Safety was measured according to standard adverse event collection as described in the adverse event section of the results.
Time Frame	Up to Follow-Up visit (30 to 40 days after study completion or treatment discontinuation)

Outcome Measure Data

Analysis Population Description

The safety population consisted of all participants who had taken at least one dose of study medication in A1481131 (NCT00159913).

Arm/Group Title	Sildenafil Low/Low Dose	Sildenafil Medium/ Medium Dose	Sildenafil High/ High Dose	Placebo/ Low Dose	Placebo/ Medium Dose	Placebo/ High Dose	Placebo Non-randomized
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil low dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil high dose in study A1481156	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
Measure Participants	42	55	77	13	19	23	5
Number [Participants]	20 47.6%	24 43.6%	41 53.2%	9 69.2%	9 47.4%	11 47.8%	3 60%

3. Primary Outcome

Title	Number of Participants Reporting at Least One Serious Adverse Event
Description	Safety was measured according to standard adverse event collection as described in the adverse event section of the results. Complete tables of the serious adverse events according to the A1481156 treatment groups are provided in the reported adverse event section.
Time Frame	Up to Follow-Up visit (30 to 40 days after study completion or treatment discontinuation)

Outcome Measure Data

Analysis Population Description

The safety population consisted of all participants who had taken at least one dose of study medication in A1481131 (NCT00159913).

Arm/Group Title	Sildenafil Low/Low Dose	Sildenafil Medium/ Medium Dose	Sildenafil High/ High Dose	Placebo/ Low Dose	Placebo/ Medium Dose	Placebo/ High Dose	Placebo Non-randomized
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil low dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil high dose in study A1481156	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
Measure Participants	42	55	77	13	19	23	5
Number [Participants]	13 31%	33 60%	38 49.4%	1 7.7%	4 21.1%	10 43.5%	0 0%

4. Primary Outcome

Title	Number of Participants Reporting Treatment-related Serious Adverse Events
Description	All serious adverse events regardless of treatment group or suspected relationship to study drug were reported. Investigators were to provide independent determination of possible causality of any serious adverse event.
Time Frame	Up to Follow-Up visit (30 to 40 days after study completion or treatment discontinuation)

Outcome Measure Data

Analysis Population Description

The safety population consisted of all participants who had taken at least one dose of study medication in A1481131 (NCT00159913).

Arm/Group Title	Sildenafil Low/Low Dose	Sildenafil Medium/ Medium Dose	Sildenafil High/ High Dose	Placebo/ Low Dose	Placebo/ Medium Dose	Placebo/ High Dose	Placebo Non-randomized
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil low dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil high dose in study A1481156	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
Measure Participants	42	55	77	13	19	23	5
Number [Participants]	1 2.4%	1 1.8%	4 5.2%	0 0%	0 0%	0 0%	0 0%

5. Primary Outcome

Title	Number of Deaths Reported in the Study Prior to the Data Monitoring Committee (DMC) Recommendation of Dose Down Titration
Description	Deaths were reported immediately independent of the circumstances or suspected cause at any time during the study through the last follow-up visit or 30 days after the last administration of study drug, whichever comes later.
Time Frame	Pre-DMC Recommendation dose down titration (04 August 2011)

Outcome Measure Data

Analysis Population Description

The safety population consisted of all participants who had taken at least one dose of study medication in A1481131 (NCT00159913).

Arm/Group Title	Sildenafil Low Dose	Sildenafil Medium Dose	Sildenafil High Dose
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913) and continued in the low dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil low dose in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and continued in the medium dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913)and continued in the high dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil high dose in the extension study A1481156
Measure Participants	55	74	100
Number [Participants]	5 11.9%	10 18.2%	22 28.6%

6. Primary Outcome

Title	Number of Deaths Reported During This Study
Description	Deaths were reported immediately independent of the circumstances or suspected cause at any time during the study through the last follow-up visit or 30 days after the last administration of study drug, whichever comes later.
Time Frame	Last follow-up visit or 30 days after the last administration of study drug

Outcome Measure Data

Analysis Population Description

The safety population consisted of all participants who had taken at least one dose of study medication in A1481131 (NCT00159913).

Arm/Group Title	Sildenafil Low Dose	Sildenafil Medium Dose	Sildenafil High Dose
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913)and continued in the low dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil low dose in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and continued in the medium dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913)and continued in the high dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil high dose in the extension study A1481156
Measure Participants	55	74	100
Number [Participants]	5 11.9%	13 23.6%	24 31.2%

7. Primary Outcome

Title	Discontinuation Due to Intolerability
Description	Participant who experienced drug-related intolerance, the participant's dose was reduced by 50%. If, after a dose reduction, the participant continued to appear intolerant, they were discontinued from study treatment.
Time Frame	Throughout the treatment duration (median treatment duration 1689 to 1744 days)

Outcome Measure Data

Analysis Population Description

Safety population included all randomly assigned participants who took at least 1 dose of study medication in Study A1481131 (NCT00159913).

Arm/Group Title	Sildenafil Low Dose	Sildenafil Medium Dose	Sildenafil High Dose
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913)and continued in the low dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil low dose in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and continued in the medium dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913)and continued in the high dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil high dose in the extension study A1481156
Measure Participants	55	74	100
Number [Participants]	2 4.8%	1 1.8%	3 3.9%

8. Primary Outcome

Title	Downtitration in Dose Due to Intolerability.
Description	Based on review of the survival data, DMC concluded that the high dose of sildenafil was associated with a harmful effect on survival when compared to the low dose. The DMC also expressed concern as to the potential dose-response relationship between increasing dose and mortality. Therefore, on 04 August 2011, the DMC recommended discontinuation of the 40 mg and 80 mg three times a day (TID) doses, as well as the 20 mg TID dose in children with body weight ≤20 kg. The protocol was amended per DMC recommendations.
Time Frame	Pre-DMC recomendation (04 August 2011)

Outcome Measure Data

Analysis Population Description

Safety population included all randomly assigned participants who took at least 1 dose of study medication in Study A1481131 (NCT00159913).

Arm/Group Title	Sildenafil Low/Low Dose	Sildenafil Medium/ Medium Dose	Sildenafil High/ High Dose	Placebo/ Low Dose	Placebo/ Medium Dose	Placebo/ High Dose	Placebo Non-randomized
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil low dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil high dose in study A1481156	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
Measure Participants	42	55	77	13	19	23	5
Number [Participants]	0 0%	0 0%	3 3.9%	0 0%	2 10.5%	1 4.3%	0 0%

9. Primary Outcome

Title	Number of Participants With Deterioration Post Baseline in Visual Acuity Safety Tests
Description	Visual Acuity is measured either using the reduced Snellen test or via Teller cards, and was assessed in the left and right eyes separately. There were 9 lines on the reduced Snellen chart which were coded as 6/60, 6/36, 6/24, 6/18, 6/12, 6/9, 6/6, 6/5, 6/4 (where 6/60 was the easiest to read and 6/4 was the most difficult to read). If a participant experienced a visual adverse event the investigator was asked to perform additional ocular assessments either at the visit when the participant reported the visual adverse event or at an unplanned visit.
Time Frame	Week 36

Outcome Measure Data

Analysis Population Description

Safety population included all randomly assigned participants who took at least 1 dose of study medication in Study A1481131 (NCT00159913).

Arm/Group Title	Sildenafil Low/Low Dose	Sildenafil Medium/ Medium Dose	Sildenafil High/ High Dose	Placebo/ Low Dose	Placebo/ Medium Dose	Placebo/ High Dose	Placebo Non-randomized
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil low dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil high dose in study A1481156	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
Measure Participants	42	55	77	13	19	23	5
Number [Participants]	10 23.8%	11 20%	17 22.1%	0 0%	4 21.1%	4 17.4%	0 0%

10. Primary Outcome

Title	Number of Participants With Deterioration Post Baseline in Color Vision Monitoring Safety Tests.
Description	Colour vision was measured where appropriate via the Farnsworth-Munsell D-15 Hue test. This test was performed in both eyes simultaneously or just in a single specific eye. If using a single eye the same eye was used throughout the study. In case of young participants an age-and-ability-appropriate evaluation such as the Ishihara Test for Unlettered Persons were conducted.
Time Frame	Week 36

Outcome Measure Data

Analysis Population Description

Safety population included all randomly assigned participants who took at least 1 dose of study medication in Study A1481131 (NCT00159913).

Arm/Group Title	Sildenafil Low/Low Dose	Sildenafil Medium/ Medium Dose	Sildenafil High/ High Dose	Placebo/ Low Dose	Placebo/ Medium Dose	Placebo/ High Dose	Placebo Non-randomized
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil low dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil high dose in study A1481156	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
Measure Participants	42	55	77	13	19	23	5
Number [Participants]	2 4.8%	2 3.6%	1 1.3%	0 0%	0 0%	1 4.3%	1 20%

11. Primary Outcome

Title	Pediatric Cognitive Development Status at Week 16.
Description	Participant's cognitive development status was assessed at A1481156 baseline (Week 16 in A1481131; NCT00159913) using the physician assessment questions. Assessment question (i.e., compared to other children the participant's age group is this participant's cognitive development limited?) included the following criteria : severely limited, moderately limited, mildly limited and not limited.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Safety population included all randomly assigned participants who took at least 1 dose of study medication in Study A1481131 (NCT00159913). Participants with observed data were included in table.

Arm/Group Title	Sildenafil Low/Low Dose	Sildenafil Medium/ Medium Dose	Sildenafil High/ High Dose	Placebo/ Low Dose	Placebo/ Medium Dose	Placebo/ High Dose	Placebo Non-randomized
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil low dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil high dose in study A1481156	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
Measure Participants	42	55	77	13	19	23	5
Severely Limited	2 4.8%	4 7.3%	2 2.6%	0 0%	1 5.3%	1 4.3%	0 0%
Moderately Limited	5 11.9%	6 10.9%	8 10.4%	1 7.7%	5 26.3%	2 8.7%	1 20%
Mildly Limited	6 14.3%	7 12.7%	12 15.6%	1 7.7%	1 5.3%	1 4.3%	0 0%
Not Limited	26 61.9%	38 69.1%	54 70.1%	11 84.6%	12 63.2%	19 82.6%	1 20%

12. Primary Outcome

Title	Pediatric Cognitive Development Status at Week 52.
Description	Participant's cognitive development status was assessed at Week 52 using the physician assessment questions. Assessment question (i.e., compared to other children the participant's age group is this participant's cognitive development limited?) included the following criteria : severely limited, moderately limited, mildly limited and not limited.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Safety population included all randomly assigned participants who took at least 1 dose of study medication in Study A1481131 (NCT00159913). Participants with observed data were included in table.

Arm/Group Title	Sildenafil Low/Low Dose	Sildenafil Medium/ Medium Dose	Sildenafil High/ High Dose	Placebo/ Low Dose	Placebo/ Medium Dose	Placebo/ High Dose
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil low dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil high dose in study A1481156
Measure Participants	42	55	77	13	19	23
Severely Limited	1 2.4%	1 1.8%	2 2.6%	0 0%	0 0%	0 0%
Moderately Limited	5 11.9%	10 18.2%	6 7.8%	1 7.7%	5 26.3%	2 8.7%
Mildly Limited	3 7.1%	5 9.1%	8 10.4%	0 0%	3 15.8%	3 13%
Not Limited	27 64.3%	36 65.5%	50 64.9%	11 84.6%	10 52.6%	15 65.2%

13. Primary Outcome

Title	Pediatric Motor Development Status at Week 16.
Description	Participant's motor development status was assessed at A1481156 baseline (Week 16 in A1481131; NCT00159913) using the physician assessment questions. Assessment question (i.e., compared to other children the participant's age group is this participant's motor development limited?) included the following criteria : severely limited, moderately limited, mildly limited and not limited.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Safety population included all randomly assigned participants who took at least 1 dose of study medication in Study A1481131 (NCT00159913). Participants with observed data were included in table.

Arm/Group Title	Sildenafil Low/Low Dose	Sildenafil Medium/ Medium Dose	Sildenafil High/ High Dose	Placebo/ Low Dose	Placebo/ Medium Dose	Placebo/ High Dose	Placebo Non-randomized
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil low dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil high dose in study A1481156	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
Measure Participants	42	55	77	13	19	23	5
Severely Limited	0 0%	0 0%	0 0%	0 0%	1 5.3%	0 0%	0 0%
Moderately Limited	5 11.9%	5 9.1%	7 9.1%	0 0%	4 21.1%	1 4.3%	1 20%
Mildly Limited	10 23.8%	11 20%	20 26%	1 7.7%	5 26.3%	2 8.7%	0 0%
Not Limited	24 57.1%	39 70.9%	49 63.6%	12 92.3%	9 47.4%	20 87%	1 20%

14. Primary Outcome

Title	Pediatric Motor Development Status at Week 52
Description	Participant's motor development status was assessed at Week 52 using the physician assessment questions. Assessment question (i.e., compared to other children the participant's age group is this participant's motor development limited?) included the following criteria : severely limited, moderately limited, mildly limited and not limited.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Safety population included all randomly assigned participants who took at least 1 dose of study medication in Study A1481131 (NCT00159913). Participants with observed data were included in table.

Arm/Group Title	Sildenafil Low/Low Dose	Sildenafil Medium/ Medium Dose	Sildenafil High/ High Dose	Placebo/ Low Dose	Placebo/ Medium Dose	Placebo/ High Dose
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil low dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil high dose in study A1481156
Measure Participants	42	55	77	13	19	23
Severely Limited	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Moderately Limited	4 9.5%	9 16.4%	5 6.5%	0 0%	2 10.5%	0 0%
Mildly Limited	8 19%	8 14.5%	15 19.5%	3 23.1%	6 31.6%	3 13%
Not Limited	24 57.1%	35 63.6%	46 59.7%	9 69.2%	10 52.6%	17 73.9%

15. Secondary Outcome

Title	Peak Volume of Oxygen (VO2) Consumed at Year 1 Using a Bicycle Ergometry Cardiopulmonary Exercise Test (CPX)
Description	Exercise Tolerance Test (CPX test) was performed on developmentally able participants to determine the peak volume of VO2 consumed. Participants were assumed to be developmentally able if they had a CPX exercise assessment at any visit during study A1481131 (NCT00159913). The CPX tests were performed as close to trough plasma levels of sildenafil as possible, i.e., prior to dosing and at least 4 hours after the previous dose. If participants were able to perform the CPX test in Study A1481131 (NCT00159913), they were expected to be able to perform the exercise paradigm in the extension study (A1481156) unless their clinical condition had deteriorated and the investigator considered this was unsafe for the participant
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

An ITT population included all randomized participants who took at least 1 dose of study medication in base study and certain analyses were conducted at pre-specified time points: 1, 2 years and 3, 4 and 5 years (where data quantity allowed) from A1481131 (NCT00159913) baseline. Only developmentally able participants were used for this analysis.

Arm/Group Title	Sildenafil Low Dose	Sildenafil Medium Dose	Sildenafil High Dose
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913)and continued in the low dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil low dose in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and continued in the medium dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913)and continued in the high dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil high dose in the extension study A1481156
Measure Participants	38	36	40
Mean (Standard Deviation) [mL/kg/min]	19.97 (5.17)	18.69 (5.92)	17.93 (4.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sildenafil Low/Low Dose, Sildenafil Medium/ Medium Dose
	Comments	Analyses were performed using analysis of covariance with etiology, weight, day of assessment and baseline peak VO2 as the covariates.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.253
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-7.02
	Confidence Interval	(2-Sided) 95%; -19.13 to 5.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.10
	Estimation Comments	Least square mean difference of -7.02 was calculated as ' Sildenafil Medium Dose - Low Dose'

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sildenafil Low/Low Dose, Sildenafil High/ High Dose
	Comments	Analyses were performed using analysis of covariance with etiology, weight, day of assessment and baseline peak VO2 as the covariates.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.100
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-9.84
	Confidence Interval	(2-Sided) 95%; -21.60 to 1.93
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.92
	Estimation Comments	Least square mean difference of -9.84 was calculated as ' Sildenafil High Dose - Low Dose'

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sildenafil Medium/ Medium Dose, Sildenafil High/ High Dose
	Comments	Analyses were performed using analysis of covariance with etiology, weight, day of assessment and baseline peak VO2 as the covariates.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.640
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-2.82
	Confidence Interval	(2-Sided) 95%; -14.75 to 9.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.01
	Estimation Comments	Least square mean difference of -2.82 was calculated as ' Sildenafil High Dose - Medium Dose'

16. Secondary Outcome

Title	Percentage Change From Baseline in Percent Predicted Peak VO2 at Year 1.
Description	Exercise Tolerance Test (CPX test) was performed on developmentally able participants to measure the percent predicted peak VO2 at Week 16 and Year 1. Participants were assumed to be developmentally able if they had a CPX exercise assessment at any visit during study A1481131 (NCT00159913). The CPX tests were performed as close to trough plasma levels of sildenafil as possible, i.e., prior to dosing and at least 4 hours after the previous dose. If participants were able to perform the CPX test in Study A1481131 (NCT00159913), they were expected to be able to perform the exercise paradigm in the extension study (A1481156) unless their clinical condition had deteriorated and the investigator considered this was unsafe for the participant.
Time Frame	Baseline, Year 1

Outcome Measure Data

Analysis Population Description

An ITT population included all randomized participants who took at least 1 dose of study medication in base study and certain analyses were conducted at pre-specified time points: 1, 2 years and 3, 4 and 5 years (where data quantity allowed) from A1481131 (NCT00159913) baseline. Only developmentally able participants were used for this analysis.

Arm/Group Title	Sildenafil Low/Low Dose	Sildenafil Medium/ Medium Dose	Sildenafil High/ High Dose	Placebo/ Low Dose	Placebo/ Medium Dose	Placebo/ High Dose	Placebo Non-randomized
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil low dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil high dose in study A1481156	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
Measure Participants	28	28	29	10	8	11	1
Mean (Standard Deviation) [Percent]	12.79 (22.71)	7.65 (34.57)	5.83 (23.54)	8.70 (25.99)	0.20 (22.32)	-6.13 (7.46)	NA (NA)

17. Secondary Outcome

Title	Percent Change From Baseline in Time to Maximum VO2 at Year 1
Description	Exercise Tolerance Test (CPX test) was performed on developmentally able participants to determine the time to maximum VO2. Participants were assumed to be developmentally able if they had a CPX exercise assessment at any visit during study A1481131 (NCT00159913). The CPX tests were performed as close to trough plasma levels of sildenafil as possible, i.e., prior to dosing and at least 4 hours after the previous dose. If participants were able to perform the CPX test in Study A1481131 (NCT00159913), they were expected to be able to perform the exercise paradigm in the extension study (A1481156) unless their clinical condition had deteriorated and the investigator considered this was unsafe for the participant.
Time Frame	Baseline, Year 1

Outcome Measure Data

Analysis Population Description

An ITT population included all randomized participants who took at least 1 dose of study medication in base study and certain analyses were conducted at pre-specified time points: 1, 2 years and 3, 4 and 5 years (where data quantity allowed) from A1481131 (NCT00159913) baseline. Only developmentally able participants were used for this analysis.

Arm/Group Title	Sildenafil Low/Low Dose	Sildenafil Medium/ Medium Dose	Sildenafil High/ High Dose	Placebo/ Low Dose	Placebo/ Medium Dose	Placebo/ High Dose	Placebo Non-randomized
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil low dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil high dose in study A1481156	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
Measure Participants	28	28	29	10	8	11	1
Mean (Standard Deviation) [Percent]	25.47 (35.67)	13.08 (33.42)	7.70 (33.01)	21.17 (57.25)	36.68 (101.65)	-9.64 (15.21)	NA (NA)

18. Secondary Outcome

Title	Percent Change From Baseline in Respiratory Exchange Ratio at Year 1
Description	This is the ratio of carbon dioxide (CO2) produced to O2 consumed [VCO2/VO2]. Exercise Tolerance Test was performed on developmentally able participants to determine the respiratory exchange ratio on week 16 and Year 1. Participants were assumed to be developmentally able if they had a CPX exercise assessment at any visit during study A1481131 (NCT00159913).
Time Frame	Baseline, Year 1

Outcome Measure Data

Analysis Population Description

An ITT population included all randomized participants who took at least 1 dose of study medication in base study and certain analyses were conducted at pre-specified time points: 1, 2 years and 3, 4 and 5 years (where data quantity allowed) from A1481131 (NCT00159913) baseline. Only developmentally able participants were used for this analysis.

Arm/Group Title	Sildenafil Low/Low Dose	Sildenafil Medium/ Medium Dose	Sildenafil High/ High Dose	Placebo/ Low Dose	Placebo/ Medium Dose	Placebo/ High Dose	Placebo Non-randomized
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil low dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil high dose in study A1481156	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
Measure Participants	28	28	29	10	8	11	1
Mean (Standard Deviation) [Percent]	2.15 (8.73)	5.63 (13.37)	0.68 (11.50)	-3.69 (7.24)	0.27 (11.04)	10.75 (17.76)	NA (NA)

19. Secondary Outcome

Title	Percent Change From Start of Sildenafil in Total Ventilation (VE) to Year 1
Description	Exercise Tolerance Test (CPX test) was performed on developmentally able participants to determine the total ventilation. Participants were assumed to be developmentally able if they had a CPX exercise assessment at any visit during study A1481131 (NCT00159913). The CPX tests were performed as close to trough plasma levels of sildenafil as possible, i.e., prior to dosing and at least 4 hours after the previous dose. If participants were able to perform the CPX test in Study A1481131 (NCT00159913), they were expected to be able to perform the exercise paradigm in the extension study (A1481156) unless their clinical condition had deteriorated and the investigator considered this was unsafe for the participant.
Time Frame	Year 1

Outcome Measure Data

Analysis Population Description

An ITT population included all randomized participants who took at least 1 dose of study medication in base study and certain analyses were conducted at pre-specified time points: 1, 2 years and 3, 4 and 5 years (where data quantity allowed) from A1481131 (NCT00159913) baseline. Only developmentally able participants were used for this analysis.

Arm/Group Title	Sildenafil Low Dose	Sildenafil Medium Dose	Sildenafil High Dose
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913)and continued in the low dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil low dose in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and continued in the medium dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913)and continued in the high dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil high dose in the extension study A1481156
Measure Participants	38	36	40
Mean (Standard Deviation) [Percent]	14.29 (21.38)	12.38 (32.64)	11.80 (19.79)

20. Secondary Outcome

Title	Percentage Change From Baseline in End Tidal Oxygen (O2) at Year 1.
Description	Exercise Tolerance Test (CPX test) was performed on developmentally able participants to measure the End Tidal O2 at Year 1. Participants were assumed to be developmentally able if they had a CPX exercise assessment at any visit during study A1481131 (NCT00159913). The CPX tests were performed as close to trough plasma levels of sildenafil as possible, i.e., prior to dosing and at least 4 hours after the previous dose. If participants were able to perform the CPX test in Study A1481131 (NCT00159913), they were expected to be able to perform the exercise paradigm in the extension study (A1481156) unless their clinical condition had deteriorated and the investigator considered this was unsafe for the participant.
Time Frame	Baseline, Year 1

Outcome Measure Data

Analysis Population Description

An ITT population included all randomized participants who took at least 1 dose of study medication in base study and certain analyses were conducted at pre-specified time points: 1, 2 years and 3, 4 and 5 years (where data quantity allowed) from A1481131 (NCT00159913) baseline. Only developmentally able participants were used for this analysis.

Arm/Group Title	Sildenafil Low Dose	Sildenafil Medium Dose	Sildenafil High Dose
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913)and continued in the low dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil low dose in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and continued in the medium dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913)and continued in the high dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil high dose in the extension study A1481156
Measure Participants	25	22	24
Mean (Standard Deviation) [Percent]	0.59 (3.79)	-0.52 (3.55)	0.08 (3.68)

21. Secondary Outcome

Title	Percentage Change From Baseline in End Tidal Carbon Dioxide (CO2) at Year 1.
Description	Exercise Tolerance Test (CPX test) was performed on developmentally able participants to measure the End Tidal CO2 at Year 1. Participants were assumed to be developmentally able if they had a CPX exercise assessment at any visit during study A1481131 (NCT00159913). The CPX tests were performed as close to trough plasma levels of sildenafil as possible, i.e., prior to dosing and at least 4 hours after the previous dose. If participants were able to perform the CPX test in Study A1481131 (NCT00159913), they were expected to be able to perform the exercise paradigm in the extension study (A1481156) unless their clinical condition had deteriorated and the investigator considered this was unsafe for the participant.
Time Frame	Baseline, Year 1

Outcome Measure Data

Analysis Population Description

An ITT population included all randomized participants who took at least 1 dose of study medication in base study and certain analyses were conducted at pre-specified time points: 1, 2 years and 3, 4 and 5 years (where data quantity allowed) from A1481131 (NCT00159913) baseline. Only developmentally able participants were used for this analysis.

Arm/Group Title	Sildenafil Low Dose	Sildenafil Medium Dose	Sildenafil High Dose
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913)and continued in the low dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil low dose in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and continued in the medium dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913)and continued in the high dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil high dose in the extension study A1481156
Measure Participants	24	20	22
Mean (Standard Deviation) [Percent]	7.83 (16.35)	7.68 (18.74)	13.16 (31.38)

22. Secondary Outcome

Title	Percentage Change From Baseline in Anaerobic Threshold at Year 1.
Description	Exercise Tolerance Test (CPX test) was performed on developmentally able participants to measure the anaerobic threshold at Week 16 and Year 1. Participants were assumed to be developmentally able if they had a CPX exercise assessment at any visit during study A1481131 (NCT00159913). The CPX tests were performed as close to trough plasma levels of sildenafil as possible, i.e., prior to dosing and at least 4 hours after the previous dose. If participants were able to perform the CPX test in Study A1481131 (NCT00159913), they were expected to be able to perform the exercise paradigm in the extension study (A1481156) unless their clinical condition had deteriorated and the investigator considered this was unsafe for the participant.
Time Frame	Baseline, Year 1

Outcome Measure Data

Analysis Population Description

An ITT population included all randomized participants who took at least 1 dose of study medication in base study and certain analyses were conducted at pre-specified time points: 1, 2 years and 3, 4 and 5 years (where data quantity allowed) from A1481131 (NCT00159913) baseline. Only developmentally able participants were used for this analysis.

Arm/Group Title	Sildenafil Low/Low Dose	Sildenafil Medium/ Medium Dose	Sildenafil High/ High Dose	Placebo/ Low Dose	Placebo/ Medium Dose	Placebo/ High Dose	Placebo Non-randomized
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil low dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil high dose in study A1481156	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
Measure Participants	26	27	28	10	7	10	1
Mean (Standard Deviation) [Percent]	-1.22 (23.06)	1.99 (29.54)	3.28 (29.36)	7.23 (12.31)	-3.59 (28.29)	8.96 (32.55)	NA (NA)

23. Secondary Outcome

Title	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.
Description	The WHO PH functional classification was as follows: Class I : Participants with PH but without resulting limitation of physical activity. Class II : Participants with PH resulting in slight limitation of physical activity. Class III : Participants with PH resulting in marked limitation of physical activity. Class IV : Participants with PH with inability to carry out any physical activity without symptoms. Changes from baseline in functional class were summarized at Years 1, 2, 3, and 4. Numbers of participants improving by 3 classes, improving by 2 classes, improving by 1 class, not changing, worsening by 1 class, worsening by 2 classes or worsening by 3 classes from A1481131 baseline at Years 1, 2, 3 and 4 were evaluated.
Time Frame	Baseline, Year 1

Outcome Measure Data

Analysis Population Description

An ITT population included all randomly assigned participants who took at least 1 dose of study medication in base study and certain analyses were conducted at pre-specified time points: 1, 2 years and 3, 4 and 5 years (where data quantity allowed) from A1481131 (NCT00159913) baseline.

Arm/Group Title	Sildenafil Low Dose	Sildenafil Medium Dose	Sildenafil High Dose
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913)and continued in the low dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil low dose in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and continued in the medium dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913)and continued in the high dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil high dose in the extension study A1481156
Measure Participants	55	74	100
Improved by 3 Classes	0 0%	0 0%	0 0%
Improved by 2 Classes	1 2.4%	0 0%	1 1.3%
Improved by 1 Class	13 31%	15 27.3%	19 24.7%
No change	30 71.4%	48 87.3%	64 83.1%
Worsened by 1 Class	4 9.5%	6 10.9%	3 3.9%
Worsened by 2 Classes	1 2.4%	0 0%	0 0%
Worsened by 3 Classes	0 0%	0 0%	0 0%
Discontinued	5 11.9%	4 7.3%	10 13%
Died	0 0%	0 0%	1 1.3%
Missing	1 2.4%	1 1.8%	2 2.6%

24. Secondary Outcome

Title	Summary of Shift in Changes From Start of Sildenafil in WHO PH Functional Class by A1481156 Treatment Group at Year 2.
Description	The WHO PH functional classification was as follows: Class I : Participants with PH but without resulting limitation of physical activity. Class II : Participants with PH resulting in slight limitation of physical activity. Class III : Participants with PH resulting in marked limitation of physical activity. Class IV : Participants with PH with inability to carry out any physical activity without symptoms. Changes from baseline in functional class were summarised at Years 1, 2, 3, and 4. Numbers of participants improving by 3 classes, improving by 2 classes, improving by 1 class, not changing, worsening by 1 class, worsening by 2 classes or worsening by 3 classes from A1481131 baseline at Years 1, 2, 3 and 4 were evaluated.
Time Frame	Baseline, Year 2

Outcome Measure Data

Analysis Population Description

An ITT population included all randomly assigned participants who took at least 1 dose of study medication in base study and certain analyses were conducted at pre-specified time points: 1, 2 years and 3, 4 and 5 years (where data quantity allowed) from A1481131 (NCT00159913) baseline.

Arm/Group Title	Sildenafil Low Dose	Sildenafil Medium Dose	Sildenafil High Dose
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913)and continued in the low dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil low dose in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and continued in the medium dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913)and continued in the high dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil high dose in the extension study A1481156
Measure Participants	55	74	100
Improved by 3 Classes	0 0%	0 0%	0 0%
Improved by 2 Classes	0 0%	1 1.8%	1 1.3%
Improved by 1 Class	11 26.2%	11 20%	16 20.8%
No change	28 66.7%	47 85.5%	55 71.4%
Worsened by 1 Class	3 7.1%	2 3.6%	5 6.5%
Worsened by 2 Classes	0 0%	0 0%	0 0%
Worsened by 3 Classes	0 0%	0 0%	0 0%
Discontinued	9 21.4%	9 16.4%	16 20.8%
Died	1 2.4%	2 3.6%	5 6.5%
Missing	3 7.1%	2 3.6%	2 2.6%

25. Secondary Outcome

Title	Summary of Shift in Changes From Start of Sildenafil in WHO PH Functional Class by A1481156 Treatment Group at Year 3.
Description	The WHO PH functional classification was as follows: Class I : Participants with PH but without resulting limitation of physical activity. Class II : Participants with PH resulting in slight limitation of physical activity. Class III : Participants with PH resulting in marked limitation of physical activity. Class IV : Participants with PH with inability to carry out any physical activity without symptoms. Changes from baseline in functional class were summarised at Years 1, 2, 3, and 4. Numbers of participants improving by 3 classes, improving by 2 classes, improving by 1 class, not changing, worsening by 1 class, worsening by 2 classes or worsening by 3 classes from A1481131 (NCT00159913) baseline at Years 1, 2, 3 and 4 were evaluated.
Time Frame	Baseline, Year 3

Outcome Measure Data

Analysis Population Description

An ITT population included all randomized participants who took at least 1 dose of study medication in base study and certain analyses were conducted at pre-specified time points: 1, 2 years and 3, 4 and 5 years (where data quantity allowed) from A1481131 (NCT00159913) baseline.

Arm/Group Title	Sildenafil Low Dose	Sildenafil Medium Dose	Sildenafil High Dose
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913)and continued in the low dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil low dose in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and continued in the medium dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913)and continued in the high dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil high dose in the extension study A1481156
Measure Participants	55	74	100
Improved by 3 Classes	0 0%	0 0%	0 0%
Improved by 2 Classes	1 2.4%	0 0%	1 1.3%
Improved by 1 Class	11 26.2%	16 29.1%	17 22.1%
No change	21 50%	36 65.5%	44 57.1%
Worsened by 1 Class	3 7.1%	3 5.5%	5 6.5%
Worsened by 2 Classes	1 2.4%	0 0%	1 1.3%
Worsened by 3 Classes	0 0%	0 0%	0 0%
Discontinued	14 33.3%	13 23.6%	19 24.7%
Died	2 4.8%	3 5.5%	9 11.7%
Missing	2 4.8%	3 5.5%	4 5.2%

26. Secondary Outcome

Title	Summary of Shift in Changes From Start of Sildenafil in WHO PH Functional Class by A1481156 Treatment Group at Year 4.
Description	The WHO PH functional classification was as follows: Class I : Participants with PH but without resulting limitation of physical activity. Class II : Participants with PH resulting in slight limitation of physical activity. Class III : Participants with PH resulting in marked limitation of physical activity. Class IV : Participants with PH with inability to carry out any physical activity without symptoms. Changes from baseline in functional class were summarised at Years 1, 2, 3, and 4. Numbers of participants improving by 3 classes, improving by 2 classes, improving by 1 class, not changing, worsening by 1 class, worsening by 2 classes or worsening by 3 classes from A1481131 baseline at Years 1, 2, 3 and 4 were evaluated.
Time Frame	Baseline, Year 4

Outcome Measure Data

Analysis Population Description

An ITT population included all randomly assigned participants who took at least 1 dose of study medication in base study and certain analyses were conducted at pre-specified time points: 1, 2 years and 3, 4 and 5 years (where data quantity allowed) from A1481131 (NCT00159913) baseline.

Arm/Group Title	Sildenafil Low Dose	Sildenafil Medium Dose	Sildenafil High Dose
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913)and continued in the low dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil low dose in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and continued in the medium dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913)and continued in the high dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil high dose in the extension study A1481156
Measure Participants	55	74	100
Improved by 3 Classes	0 0%	0 0%	0 0%
Improved by 2 Classes	0 0%	0 0%	2 2.6%
Improved by 1 Class	13 31%	14 25.5%	16 20.8%
No change	15 35.7%	29 52.7%	41 53.2%
Worsened by 1 Class	6 14.3%	4 7.3%	5 6.5%
Worsened by 2 Classes	1 2.4%	2 3.6%	1 1.3%
Worsened by 3 Classes	0 0%	0 0%	0 0%
Discontinued	15 35.7%	18 32.7%	20 26%
Died	2 4.8%	5 9.1%	13 16.9%
Missing	3 7.1%	2 3.6%	2 2.6%

27. Secondary Outcome

Title	Additions From Baseline in Background Therapy up to the End of Study
Description	This was defined as an addition or discontinuation in the class(es) of drugs used as background medication (e.g., anticoagulants, oxygen, diuretics, calcium channel blockers, and digoxin) compared to baseline of Study A1481131 (NCT00159913).
Time Frame	Up to the end of study

Outcome Measure Data

Analysis Population Description

An ITT population included all randomly assigned participants who took at least 1 dose of study medication in base study and certain analyses were conducted at pre-specified time points: 1, 2 years and 3, 4 and 5 years (where data quantity allowed) from A1481131 (NCT00159913) baseline.

Arm/Group Title	Sildenafil Low/Low Dose	Sildenafil Medium/ Medium Dose	Sildenafil High/ High Dose	Placebo/ Low Dose	Placebo/ Medium Dose	Placebo/ High Dose	Placebo Non-randomized
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil low dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil high dose in study A1481156	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
Measure Participants	42	55	77	13	19	23	5
All Classes (N = 18, 26, 43, 7, 8, 14, 4)	6 14.3%	5 9.1%	11 14.3%	2 15.4%	1 5.3%	2 8.7%	1 20%
At least one class (N = 42, 55, 77, 13, 19, 23, 5)	13 31%	13 23.6%	23 29.9%	3 23.1%	5 26.3%	2 8.7%	1 20%

28. Secondary Outcome

Title	Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF28) as Assessed by the Psychosocial Scale at Year 1.
Description	CHQ: 50-item, 15 subscale parent or legal guardian assessed instrument of child's physical, emotional, social well-being, and relative burden of disease on the parents; rated on Likert-type scale: range 0 to 100; higher scores indicate a more positive health status. Global indicators for Physical Health and Psychosocial Health are weighted composites derived from subscale items using scoring algorithms (transformed scores); range 0 to 100: higher scores indicate more positive health status.
Time Frame	Baseline, Year 1

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who took at least 1 dose of study drug in base study; certain analyses were conducted at pre-specified time points: 1, 2 years and 3, 4, 5 years (where data quantity allowed) from A1481131 (NCT00159913) baseline. Participants >= 5 years at baseline with questionnaire translated were included.

Arm/Group Title	Sildenafil Low/Low Dose	Sildenafil Medium/ Medium Dose	Sildenafil High/ High Dose	Placebo/ Low Dose	Placebo/ Medium Dose	Placebo/ High Dose	Placebo Non-randomized
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil low dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil high dose in study A1481156	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
Measure Participants	34	30	45	11	14	15	1
Mean (Standard Deviation) [Units on a scale]	5.63 (7.70)	3.92 (10.25)	3.48 (12.55)	13.74 (12.42)	5.30 (9.30)	4.27 (12.19)	NA (NA)

29. Secondary Outcome

Title	Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF28) as Assessed by the Physical Scale at Year 1.
Description	CHQ: 50-item, 15 subscale parent or legal guardian assessed instrument of child's physical, emotional, social well-being, and relative burden of disease on the parents; rated on Likert-type scale: range 0 to 100; higher scores indicate a more positive health status. Global indicators for Physical Health and Psychosocial Health are weighted composites derived from subscale items using scoring algorithms (transformed scores); range 0 to 100: higher scores indicate more positive health status.
Time Frame	Baseline, Year 1

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who took at least 1 dose of study drug in base study; certain analyses were conducted at pre-specified time points: 1, 2 years and 3, 4, 5 years (where data quantity allowed) from A1481131 (NCT00159913) baseline. Participants >= 5 years at baseline with questionnaire translated were included.

Arm/Group Title	Sildenafil Low/Low Dose	Sildenafil Medium/ Medium Dose	Sildenafil High/ High Dose	Placebo/ Low Dose	Placebo/ Medium Dose	Placebo/ High Dose	Placebo Non-randomized
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913) and in the extension study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil low dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in study A1481156	Participants randomized to placebo in study A1481131 (NCT00159913) and randomized to sildenafil high dose in study A1481156	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
Measure Participants	34	30	45	11	14	15	1
Mean (Standard Deviation) [Units on a scale]	14.29 (11.06)	9.34 (13.45)	5.91 (10.17)	8.51 (13.27)	9.86 (17.93)	4.64 (12.03)	NA (NA)

30. Secondary Outcome

Title	Participant (Parent) Global Assessment at Year 1
Description	The participant (parent) global assessment of disease severity was assessed at Year 1 in this extension study. The number and percentage of participants markedly improved, moderately improved, mild improvement, no change, slightly worse, moderately worse, markedly worse were evaluated. Participants who withdrew from study treatment after at least 10 weeks of treatment were requested to perform the global assessments.
Time Frame	Year 1

Outcome Measure Data

Analysis Population Description

An ITT population included all randomly assigned participants who took at least 1 dose of study medication in base study and certain analyses were conducted at pre-specified time points: 1, 2 years and 3, 4 and 5 years (where data quantity allowed) from A1481131 (NCT00159913) baseline.

Arm/Group Title	Sildenafil Low Dose	Sildenafil Medium Dose	Sildenafil High Dose
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913)and continued in the low dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil low dose in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and continued in the medium dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913)and continued in the high dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil high dose in the extension study A1481156
Measure Participants	55	74	100
Markedly Improved	9 21.4%	14 25.5%	21 27.3%
Moderately Improved	13 31%	27 49.1%	26 33.8%
Mild Improvement	12 28.6%	15 27.3%	15 19.5%
No Change	13 31%	6 10.9%	21 27.3%
Slightly Worse	1 2.4%	2 3.6%	0 0%
Moderately Worse	0 0%	1 1.8%	0 0%
Markedly Worse	0 0%	0 0%	0 0%
Discontinued	5 11.9%	4 7.3%	10 13%
Died	0 0%	0 0%	1 1.3%
Missing	2 4.8%	5 9.1%	6 7.8%

31. Secondary Outcome

Title	Physician Global Assessment at Year 1
Description	The physician global assessment of disease severity was assessed at Year 1 in this extension study. The number and percentage of participants with markedly improved, moderately improved, mild improvement, no change, slightly worse, moderately worse, markedly worse were evaluated. Participants who withdrew from study treatment after at least 10 weeks of treatment were requested to perform the global assessments.
Time Frame	Year 1

Outcome Measure Data

Analysis Population Description

An ITT population included all randomly assigned participants who took at least 1 dose of study medication in base study and certain analyses were conducted at pre-specified time points: 1, 2 years and 3, 4 and 5 years (where data quantity allowed) from A1481131 (NCT00159913) baseline.

Arm/Group Title	Sildenafil Low Dose	Sildenafil Medium Dose	Sildenafil High Dose
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913)and continued in the low dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil low dose in the extension study A1481156	Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and continued in the medium dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in the extension study A1481156	Participants randomized to sildenafil high dose in study A1481131 (NCT00159913)and continued in the high dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil high dose in the extension study A1481156
Measure Participants	55	74	100
Markedly Improved	6 14.3%	6 10.9%	6 7.8%
Moderately Improved	8 19%	18 32.7%	27 35.1%
Mild Improvement	19 45.2%	26 47.3%	37 48.1%
No Change	15 35.7%	16 29.1%	17 22.1%
Slightly Worse	1 2.4%	1 1.8%	0 0%
Moderately Worse	0 0%	1 1.8%	0 0%
Markedly Worse	0 0%	0 0%	0 0%
Discontinued	5 11.9%	4 7.3%	10 13%
Died	0 0%	0 0%	1 1.3%
Missing	1 2.4%	2 3.6%	2 2.6%

Adverse Events

Time Frame	Up to Follow-Up visit (30 to 40 days after study completion or treatment discontinuation)
Adverse Event Reporting Description	The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Sildenafil Low Dose		Sildenafil Medium Dose		Sildenafil High Dose
Arm/Group Description	Participants randomized to sildenafil low dose in study A1481131 (NCT00159913)and continued in the low dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil low dose in the extension study A1481156		Participants randomized to sildenafil medium dose in study A1481131 (NCT00159913) and continued in the medium dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil medium dose in the extension study A1481156		Participants randomized to sildenafil high dose in study A1481131 (NCT00159913)and continued in the high dose group in the extension study A1481156, and participants randomized to placebo dose in study A1481131 (NCT00159913) and randomized to sildenafil high dose in the extension study A1481156
All Cause Mortality
	Sildenafil Low Dose		Sildenafil Medium Dose		Sildenafil High Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Sildenafil Low Dose		Sildenafil Medium Dose		Sildenafil High Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/55 (25.5%)		37/74 (50%)		48/100 (48%)
Blood and lymphatic system disorders
Anaemia	0/55 (0%)		0/74 (0%)		1/100 (1%)
Polycythaemia	0/55 (0%)		0/74 (0%)		1/100 (1%)
Cardiac disorders
Bradycardia	0/55 (0%)		0/74 (0%)		1/100 (1%)
Cardiac failure	2/55 (3.6%)		2/74 (2.7%)		6/100 (6%)
Cardiac failure congestive	1/55 (1.8%)		0/74 (0%)		1/100 (1%)
Cardiogenic shock	0/55 (0%)		1/74 (1.4%)		2/100 (2%)
Cyanosis	1/55 (1.8%)		1/74 (1.4%)		0/100 (0%)
Pericardial effusion	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Right ventricular failure	2/55 (3.6%)		3/74 (4.1%)		3/100 (3%)
Supraventricular tachycardia	1/55 (1.8%)		0/74 (0%)		0/100 (0%)
Tachycardia paroxysmal	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Ventricular fibrillation	0/55 (0%)		0/74 (0%)		2/100 (2%)
Ventricular arrhythmia	0/55 (0%)		0/74 (0%)		1/100 (1%)
Congenital, familial and genetic disorders
Cystic fibrosis	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Eisenmenger's syndrome	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Hip dysplasia	1/55 (1.8%)		1/74 (1.4%)		0/100 (0%)
Ventricular septal defect	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Ear and labyrinth disorders
Deafness neurosensory	0/55 (0%)		0/74 (0%)		1/100 (1%)
Eye disorders
Corneal oedema	0/55 (0%)		0/74 (0%)		1/100 (1%)
Keratoconus	0/55 (0%)		0/74 (0%)		1/100 (1%)
Vision blurred	1/55 (1.8%)		0/74 (0%)		0/100 (0%)
Gastrointestinal disorders
Abdominal pain	0/55 (0%)		0/74 (0%)		1/100 (1%)
Ascites	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Dental caries	0/55 (0%)		1/74 (1.4%)		3/100 (3%)
Diarrhoea	0/55 (0%)		2/74 (2.7%)		0/100 (0%)
Duodenal ulcer	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Enteritis	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Enterocolitis	1/55 (1.8%)		0/74 (0%)		0/100 (0%)
Food poisoning	0/55 (0%)		0/74 (0%)		1/100 (1%)
Haematemesis	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Haematochezia	1/55 (1.8%)		0/74 (0%)		0/100 (0%)
Vomiting	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
General disorders
Chest pain	3/55 (5.5%)		0/74 (0%)		2/100 (2%)
Disease progression	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Gait disturbance	1/55 (1.8%)		0/74 (0%)		0/100 (0%)
Pyrexia	0/55 (0%)		0/74 (0%)		3/100 (3%)
Infections and infestations
Acute tonsillitis	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Bacteraemia	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Brain abscess	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Bronchitis	1/55 (1.8%)		1/74 (1.4%)		3/100 (3%)
Bronchopneumonia	1/55 (1.8%)		1/74 (1.4%)		3/100 (3%)
Cellulitis	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Dengue fever	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Gastroenteritis	0/55 (0%)		3/74 (4.1%)		3/100 (3%)
Gastroenteritis salmonella	1/55 (1.8%)		0/74 (0%)		0/100 (0%)
Gastroenteritis viral	0/55 (0%)		1/74 (1.4%)		1/100 (1%)
Gastrointestinal infection	0/55 (0%)		0/74 (0%)		1/100 (1%)
Gastrointestinal viral infection	0/55 (0%)		0/74 (0%)		1/100 (1%)
Gingivitis	1/55 (1.8%)		0/74 (0%)		0/100 (0%)
Laryngitis	0/55 (0%)		1/74 (1.4%)		1/100 (1%)
Lower respiratory tract infection	0/55 (0%)		0/74 (0%)		1/100 (1%)
Lung infection	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Peritonitis	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Peritonsillar abscess	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Pharyngitis	1/55 (1.8%)		1/74 (1.4%)		0/100 (0%)
Pneumonia	1/55 (1.8%)		7/74 (9.5%)		10/100 (10%)
Pneumonia bacterial	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Pneumonia respiratory syncytial viral	0/55 (0%)		0/74 (0%)		1/100 (1%)
Respiratory tract infection	0/55 (0%)		0/74 (0%)		1/100 (1%)
Tonsillitis	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Tooth abscess	1/55 (1.8%)		0/74 (0%)		0/100 (0%)
Upper respiratory tract infection	0/55 (0%)		1/74 (1.4%)		6/100 (6%)
Urinary tract infection	0/55 (0%)		0/74 (0%)		3/100 (3%)
Viral infection	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Injury, poisoning and procedural complications
Contusion	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Exposure via father	1/55 (1.8%)		0/74 (0%)		0/100 (0%)
Hip fracture	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Skull fracture	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Subdural haematoma	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Tibia fracture	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Toxicity to various agents	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Upper limb fracture	1/55 (1.8%)		0/74 (0%)		0/100 (0%)
Investigations
Catheterisation cardiac	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Oxygen saturation decreased	0/55 (0%)		0/74 (0%)		1/100 (1%)
Pulmonary arterial pressure increased	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Metabolism and nutrition disorders
Dehydration	1/55 (1.8%)		0/74 (0%)		1/100 (1%)
Electrolyte imbalance	0/55 (0%)		1/74 (1.4%)		1/100 (1%)
Hypoalbuminaemia	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Nervous system disorders
Convulsion	1/55 (1.8%)		1/74 (1.4%)		0/100 (0%)
Dizziness	1/55 (1.8%)		0/74 (0%)		1/100 (1%)
Headache	0/55 (0%)		0/74 (0%)		1/100 (1%)
Loss of consciousness	1/55 (1.8%)		0/74 (0%)		0/100 (0%)
Syncope	2/55 (3.6%)		2/74 (2.7%)		1/100 (1%)
Transient ischaemic attack	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Psychiatric disorders
Anorexia nervosa	1/55 (1.8%)		0/74 (0%)		0/100 (0%)
Renal and urinary disorders
Enuresis	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Reproductive system and breast disorders
Menorrhagia	1/55 (1.8%)		0/74 (0%)		0/100 (0%)
Respiratory, thoracic and mediastinal disorders
Adenoidal hypertrophy	0/55 (0%)		0/74 (0%)		1/100 (1%)
Bronchospasm	0/55 (0%)		0/74 (0%)		1/100 (1%)
Cough	0/55 (0%)		0/74 (0%)		1/100 (1%)
Dyspnoea	1/55 (1.8%)		0/74 (0%)		0/100 (0%)
Dyspnoea exertional	0/55 (0%)		0/74 (0%)		1/100 (1%)
Epistaxis	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Haemoptysis	0/55 (0%)		2/74 (2.7%)		0/100 (0%)
Hypoxia	0/55 (0%)		0/74 (0%)		2/100 (2%)
Nasal turbinate hypertrophy	0/55 (0%)		0/74 (0%)		1/100 (1%)
Pneumonia aspiration	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Pulmonary arterial hypertension	0/55 (0%)		2/74 (2.7%)		7/100 (7%)
Pulmonary embolism	0/55 (0%)		0/74 (0%)		1/100 (1%)
Pulmonary haemorrhage	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Pulmonary hypertension	2/55 (3.6%)		4/74 (5.4%)		5/100 (5%)
Respiratory arrest	0/55 (0%)		0/74 (0%)		1/100 (1%)
Respiratory failure	1/55 (1.8%)		0/74 (0%)		0/100 (0%)
Sleep apnoea syndrome	0/55 (0%)		0/74 (0%)		1/100 (1%)
Stridor	0/55 (0%)		0/74 (0%)		1/100 (1%)
Tonsillar hypertrophy	0/55 (0%)		0/74 (0%)		1/100 (1%)
Skin and subcutaneous tissue disorders
Excessive granulation tissue	0/55 (0%)		0/74 (0%)		1/100 (1%)
Surgical and medical procedures
Cardiac operation	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Central venous catheterisation	0/55 (0%)		1/74 (1.4%)		0/100 (0%)
Vascular disorders
Circulatory collapse	1/55 (1.8%)		0/74 (0%)		0/100 (0%)
Hypotension	1/55 (1.8%)		0/74 (0%)		0/100 (0%)
Other (Not Including Serious) Adverse Events
	Sildenafil Low Dose		Sildenafil Medium Dose		Sildenafil High Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	51/55 (92.7%)		70/74 (94.6%)		87/100 (87%)
Endocrine disorders
Hypothyroidism	0/55 (0%)		4/74 (5.4%)		0/100 (0%)
Eye disorders
Conjunctival hyperaemia	3/55 (5.5%)		5/74 (6.8%)		6/100 (6%)
Conjunctivitis	1/55 (1.8%)		3/74 (4.1%)		9/100 (9%)
Conjunctivitis allergic	0/55 (0%)		4/74 (5.4%)		3/100 (3%)
Retinal vascular disorder	1/55 (1.8%)		4/74 (5.4%)		6/100 (6%)
Visual acuity reduced	2/55 (3.6%)		4/74 (5.4%)		5/100 (5%)
Visual impairment	3/55 (5.5%)		1/74 (1.4%)		2/100 (2%)
Gastrointestinal disorders
Abdominal pain	4/55 (7.3%)		4/74 (5.4%)		13/100 (13%)
Abdominal pain upper	3/55 (5.5%)		5/74 (6.8%)		9/100 (9%)
Dental caries	6/55 (10.9%)		3/74 (4.1%)		2/100 (2%)
Diarrhoea	10/55 (18.2%)		11/74 (14.9%)		16/100 (16%)
Dyspepsia	3/55 (5.5%)		6/74 (8.1%)		5/100 (5%)
Gastritis	2/55 (3.6%)		4/74 (5.4%)		5/100 (5%)
Nausea	2/55 (3.6%)		5/74 (6.8%)		12/100 (12%)
Vomiting	14/55 (25.5%)		13/74 (17.6%)		24/100 (24%)
General disorders
Chest pain	5/55 (9.1%)		4/74 (5.4%)		12/100 (12%)
Fatigue	4/55 (7.3%)		8/74 (10.8%)		7/100 (7%)
Pyrexia	7/55 (12.7%)		16/74 (21.6%)		16/100 (16%)
Infections and infestations
Bronchitis	10/55 (18.2%)		16/74 (21.6%)		16/100 (16%)
Bronchopneumonia	0/55 (0%)		4/74 (5.4%)		2/100 (2%)
Ear infection	3/55 (5.5%)		8/74 (10.8%)		4/100 (4%)
Gastroenteritis	4/55 (7.3%)		3/74 (4.1%)		7/100 (7%)
Influenza	10/55 (18.2%)		6/74 (8.1%)		12/100 (12%)
Laryngitis	5/55 (9.1%)		1/74 (1.4%)		4/100 (4%)
Nasopharyngitis	15/55 (27.3%)		11/74 (14.9%)		17/100 (17%)
Otitis media	2/55 (3.6%)		4/74 (5.4%)		4/100 (4%)
Pharyngitis	16/55 (29.1%)		13/74 (17.6%)		13/100 (13%)
Pharyngitis streptococcal	3/55 (5.5%)		3/74 (4.1%)		2/100 (2%)
Pneumonia	2/55 (3.6%)		4/74 (5.4%)		0/100 (0%)
Respiratory tract infection	2/55 (3.6%)		4/74 (5.4%)		5/100 (5%)
Rhinitis	6/55 (10.9%)		10/74 (13.5%)		7/100 (7%)
Sinusitis	2/55 (3.6%)		3/74 (4.1%)		8/100 (8%)
Tonsillitis	9/55 (16.4%)		6/74 (8.1%)		13/100 (13%)
Upper respiratory tract infection	9/55 (16.4%)		22/74 (29.7%)		37/100 (37%)
Urinary tract infection	3/55 (5.5%)		2/74 (2.7%)		6/100 (6%)
Varicella	3/55 (5.5%)		3/74 (4.1%)		4/100 (4%)
Investigations
Blood pressure diastolic decreased	3/55 (5.5%)		3/74 (4.1%)		4/100 (4%)
Weight decreased	3/55 (5.5%)		2/74 (2.7%)		3/100 (3%)
Metabolism and nutrition disorders
Decreased appetite	2/55 (3.6%)		2/74 (2.7%)		5/100 (5%)
Musculoskeletal and connective tissue disorders
Back pain	3/55 (5.5%)		0/74 (0%)		1/100 (1%)
Pain in extremity	5/55 (9.1%)		3/74 (4.1%)		2/100 (2%)
Nervous system disorders
Dizziness	7/55 (12.7%)		4/74 (5.4%)		10/100 (10%)
Headache	18/55 (32.7%)		18/74 (24.3%)		26/100 (26%)
Syncope	5/55 (9.1%)		7/74 (9.5%)		5/100 (5%)
Psychiatric disorders
Insomnia	3/55 (5.5%)		0/74 (0%)		1/100 (1%)
Respiratory, thoracic and mediastinal disorders
Cough	11/55 (20%)		14/74 (18.9%)		17/100 (17%)
Dyspnoea	4/55 (7.3%)		6/74 (8.1%)		6/100 (6%)
Epistaxis	6/55 (10.9%)		12/74 (16.2%)		9/100 (9%)
Haemoptysis	3/55 (5.5%)		4/74 (5.4%)		2/100 (2%)
Oropharyngeal pain	3/55 (5.5%)		5/74 (6.8%)		5/100 (5%)
Pulmonary arterial hypertension	4/55 (7.3%)		4/74 (5.4%)		9/100 (9%)
Pulmonary hypertension	2/55 (3.6%)		4/74 (5.4%)		3/100 (3%)
Rhinitis allergic	4/55 (7.3%)		1/74 (1.4%)		2/100 (2%)
Rhinorrhoea	0/55 (0%)		5/74 (6.8%)		2/100 (2%)
Skin and subcutaneous tissue disorders
Rash	3/55 (5.5%)		1/74 (1.4%)		3/100 (3%)

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.