Trial Outcomes & Findings for A Randomized, Double-Blind, Placebo-Controlled Study of Sildenafil in Children With Pulmonary Arterial Hypertension. (NCT NCT00159913)
NCT ID: NCT00159913
Last Updated: 2021-02-18
Results Overview
Peak VO2 (normalized for body weight) at trough plasma levels assessed by CPX testing (bicycle ergometry)at the end of treatment (Week 16 for those who completed the study). Mean Percent change = \[(week 16 value minus baseline mean)/mean at baseline\]\*100%.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
235 participants
Primary outcome timeframe
Baseline, Week 16
Results posted on
2021-02-18
Participant Flow
The study was conducted at 32 centers in North, Latin and South America, Europe and Asia.
Of the 324 subjects screened, 235 subjects were randomized. 234 received treatment. One subject(sildenafil medium dose group) withdrew prior to taking any study treatment as the hemodynamic entrance criteria were not met.
Participant milestones
| Measure |
Sildenafil Low Dose
Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights \> 20-45 kg and \> 45 kg, through Day 112.
Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the \>= 8-20 kg weight group.
|
Sildenafil Medium Dose
Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Sildenafil High Dose
Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Placebo
Subjects randomized to this arm recieved placebo TID (three times daily) for 112 days.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
42
|
55
|
77
|
60
|
|
Overall Study
COMPLETED
|
40
|
55
|
75
|
58
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
2
|
2
|
Reasons for withdrawal
| Measure |
Sildenafil Low Dose
Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights \> 20-45 kg and \> 45 kg, through Day 112.
Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the \>= 8-20 kg weight group.
|
Sildenafil Medium Dose
Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Sildenafil High Dose
Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Placebo
Subjects randomized to this arm recieved placebo TID (three times daily) for 112 days.
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
0
|
1
|
|
Overall Study
Protocol Violation
|
1
|
0
|
1
|
0
|
Baseline Characteristics
A Randomized, Double-Blind, Placebo-Controlled Study of Sildenafil in Children With Pulmonary Arterial Hypertension.
Baseline characteristics by cohort
| Measure |
Sildenafil Low Dose
n=42 Participants
Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights \> 20-45 kg and \> 45 kg, through Day 112.
Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the \>= 8-20 kg weight group.
|
Sildenafil Medium Dose
n=55 Participants
Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Sildenafil High Dose
n=77 Participants
Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Placebo
n=60 Participants
Subjects randomized to this arm recieved placebo TID (three times daily) for 112 days.
|
Total
n=234 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Customized
1-4 Years
|
0 participants
n=5 Participants
|
9 participants
n=7 Participants
|
19 participants
n=5 Participants
|
7 participants
n=4 Participants
|
35 participants
n=21 Participants
|
|
Age, Customized
5-12 Years
|
25 participants
n=5 Participants
|
28 participants
n=7 Participants
|
36 participants
n=5 Participants
|
37 participants
n=4 Participants
|
126 participants
n=21 Participants
|
|
Age, Customized
13-17 Years
|
17 participants
n=5 Participants
|
18 participants
n=7 Participants
|
22 participants
n=5 Participants
|
16 participants
n=4 Participants
|
73 participants
n=21 Participants
|
|
Age, Customized
>= 18 Years
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
0 participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
25 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
51 Participants
n=5 Participants
|
38 Participants
n=4 Participants
|
145 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
22 Participants
n=4 Participants
|
89 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 16Population: ITT population included all subjects randomised and who received at least one dose of study medication. All subjects developmentally able to perform the exercise test. Subjects assumed developmentally able if they had a CPX exercise assessment at any visit during study using a LOCF (end-of-treatment)approach for handling missing data.
Peak VO2 (normalized for body weight) at trough plasma levels assessed by CPX testing (bicycle ergometry)at the end of treatment (Week 16 for those who completed the study). Mean Percent change = \[(week 16 value minus baseline mean)/mean at baseline\]\*100%.
Outcome measures
| Measure |
Sildenafil Low Dose
n=24 Participants
Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights \> 20-45 kg and \> 45 kg, through Day 112.
Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the \>= 8-20 kg weight group.
|
Sildenafil Medium Dose
n=26 Participants
Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Sildenafil High Dose
n=27 Participants
Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Combined Sildenafil
n=77 Participants
This includes all subjects in the low, medium and high dose groups.
|
Placebo
n=29 Participants
Subjects randomized to this arm recieved placebo TID (three times daily) for 112 days.
|
|---|---|---|---|---|---|
|
Percent Change From Baseline in Peak Volume of Oxygen (VO2) Consumed : Intent To Treat Population
|
6.44 percent change
Standard Deviation 20.16 • Interval -6.11 to 13.73
|
13.40 percent change
Standard Deviation 19.50 • Interval 1.72 to 20.94
|
10.58 percent change
Standard Deviation 15.51 • Interval -1.64 to 17.6
|
10.24 percent change
Standard Deviation 18.39
|
0.53 percent change
Standard Deviation 15.91
|
PRIMARY outcome
Timeframe: Baseline, Week 16Population: Per Protocol Population
Peak VO2 (normalized for body weight) at trough plasma levels assessed by CPX testing (bicycle ergometry)at the end of treatment (Week 16 for those who completed the study). Mean Percent change = \[(week 16 value minus baseline mean)/mean at baseline\]\*100%.
Outcome measures
| Measure |
Sildenafil Low Dose
n=23 Participants
Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights \> 20-45 kg and \> 45 kg, through Day 112.
Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the \>= 8-20 kg weight group.
|
Sildenafil Medium Dose
n=23 Participants
Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Sildenafil High Dose
n=27 Participants
Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Combined Sildenafil
n=73 Participants
This includes all subjects in the low, medium and high dose groups.
|
Placebo
n=24 Participants
Subjects randomized to this arm recieved placebo TID (three times daily) for 112 days.
|
|---|---|---|---|---|---|
|
Percent Change From Baseline in Peak Volume of Oxygen (VO2) Consumed : Per Protocol Population
|
5.43 percent change
Standard Deviation 20.69
|
15.66 percent change
Standard Deviation 21.48
|
9.34 percent change
Standard Deviation 17.13
|
10.10 percent change
Standard Deviation 19.87
|
2.81 percent change
Standard Deviation 13.17
|
SECONDARY outcome
Timeframe: Baseline, Week 16Population: ITT population, using a LOCF (end-of-treatment) approach for handling missing data.
mPAP, a hemodynamic parameter, was measured using a pressure transducer positioned at the mid-axillary line with the patient in the supine position. Change is observed value at Week 16 minus Baseline value.
Outcome measures
| Measure |
Sildenafil Low Dose
n=39 Participants
Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights \> 20-45 kg and \> 45 kg, through Day 112.
Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the \>= 8-20 kg weight group.
|
Sildenafil Medium Dose
n=55 Participants
Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Sildenafil High Dose
n=71 Participants
Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Combined Sildenafil
n=165 Participants
This includes all subjects in the low, medium and high dose groups.
|
Placebo
n=56 Participants
Subjects randomized to this arm recieved placebo TID (three times daily) for 112 days.
|
|---|---|---|---|---|---|
|
Change From Baseline to Week 16 in Mean Pulmonary Artery Pressure (mPAP)
|
0.9 mm Hg
Standard Deviation 12.3
|
-3.9 mm Hg
Standard Deviation 12.0
|
-7.4 mm Hg
Standard Deviation 15.4
|
-4.3 mm Hg
Standard Deviation 13.9
|
-0.4 mm Hg
Standard Deviation 15.9
|
SECONDARY outcome
Timeframe: Baseline, Week 16Population: ITT population, LOCF
PVRI equals Pulmonary Vascular Resistance (PVR) times Body Surface Area (BSA). Wood unit = 80dyn•s/cm5. Change is observed value at Week 16 minus Baseline value.
Outcome measures
| Measure |
Sildenafil Low Dose
n=36 Participants
Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights \> 20-45 kg and \> 45 kg, through Day 112.
Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the \>= 8-20 kg weight group.
|
Sildenafil Medium Dose
n=49 Participants
Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Sildenafil High Dose
n=67 Participants
Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Combined Sildenafil
n=152 Participants
This includes all subjects in the low, medium and high dose groups.
|
Placebo
n=50 Participants
Subjects randomized to this arm recieved placebo TID (three times daily) for 112 days.
|
|---|---|---|---|---|---|
|
Change From Baseline to Week 16 in Pulmonary Vascular Resistance Index (PVRI)
|
0.1 wood units. m2
Standard Deviation 10.9
|
-2.9 wood units. m2
Standard Deviation 11.5
|
-5.1 wood units. m2
Standard Deviation 14.7
|
-3.2 wood units. m2
Standard Deviation 13.0
|
1.6 wood units. m2
Standard Deviation 9.2
|
SECONDARY outcome
Timeframe: Baseline, Week 16Population: ITT population, LOCF (end-of-treatment) approach for handling missing values.
RER is the ratio of carbon dioxide produced to oxygen consumed \[VCO2/VO2\]). Percent change is \[(Week 16 value minus Baseline value)/Baseline value\] \* 100%
Outcome measures
| Measure |
Sildenafil Low Dose
n=24 Participants
Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights \> 20-45 kg and \> 45 kg, through Day 112.
Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the \>= 8-20 kg weight group.
|
Sildenafil Medium Dose
n=26 Participants
Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Sildenafil High Dose
n=27 Participants
Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Combined Sildenafil
n=77 Participants
This includes all subjects in the low, medium and high dose groups.
|
Placebo
n=29 Participants
Subjects randomized to this arm recieved placebo TID (three times daily) for 112 days.
|
|---|---|---|---|---|---|
|
Percent Change From Baseline to Week 16 in: Respiratory Exchange Ratio (RER)
|
-0.00 percent change
Standard Deviation 0.13
|
-0.05 percent change
Standard Deviation 0.12
|
-0.02 percent change
Standard Deviation 0.11
|
-0.03 percent change
Standard Deviation 0.12
|
-0.03 percent change
Standard Deviation 0.11
|
SECONDARY outcome
Timeframe: Baseline, Week 16Population: ITT population, LOCF (end-of-treatment) approach for handling missing values.
Time to maximum VO2 was assessed on the subset of subjects who are developmentally able to perform the exercise test. Percent change is \[(value at Week 16 minus Baseline value)/Baseline value\] \* 100%
Outcome measures
| Measure |
Sildenafil Low Dose
n=24 Participants
Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights \> 20-45 kg and \> 45 kg, through Day 112.
Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the \>= 8-20 kg weight group.
|
Sildenafil Medium Dose
n=26 Participants
Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Sildenafil High Dose
n=27 Participants
Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Combined Sildenafil
n=77 Participants
This includes all subjects in the low, medium and high dose groups.
|
Placebo
n=29 Participants
Subjects randomized to this arm recieved placebo TID (three times daily) for 112 days.
|
|---|---|---|---|---|---|
|
Percent Change From Baseline to Week 16 in Time to Maximum Volume of Oxygen Consumed (VO2)
|
64.83 percent change
Standard Deviation 103.69
|
64.42 percent change
Standard Deviation 102.70
|
31.33 percent change
Standard Deviation 107.04
|
52.95 percent change
Standard Deviation 104.40
|
8.84 percent change
Standard Deviation 96.09
|
SECONDARY outcome
Timeframe: Baseline, Week 16Population: ITT population, using LOCF (end of treatment) approach for handling missing data
Change calculated as (mean PAP - PCWP)/COpulm in PVR is observed value at Week 16 minus Baseline value.
Outcome measures
| Measure |
Sildenafil Low Dose
n=36 Participants
Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights \> 20-45 kg and \> 45 kg, through Day 112.
Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the \>= 8-20 kg weight group.
|
Sildenafil Medium Dose
n=49 Participants
Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Sildenafil High Dose
n=67 Participants
Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Combined Sildenafil
n=152 Participants
This includes all subjects in the low, medium and high dose groups.
|
Placebo
n=50 Participants
Subjects randomized to this arm recieved placebo TID (three times daily) for 112 days.
|
|---|---|---|---|---|---|
|
Change From Baseline to Week 16 in Pulmonary Vascular Resistance (PVR)
|
-0.1 wood units
Standard Deviation 10.4
|
-3.3 wood units
Standard Deviation 10.5
|
-5.2 wood units
Standard Deviation 15.7
|
-3.4 wood units
Standard Deviation 13.1
|
0.1 wood units
Standard Deviation 11.8
|
SECONDARY outcome
Timeframe: Baseline, Week 16Population: ITT population, using LOCF (end of treatment) approach for handling missing data.
CI is observed value at Week 16 minus Baseline value. Calculated as cardiac output in systemic circulation (COsys) / body surface area (BSA).
Outcome measures
| Measure |
Sildenafil Low Dose
n=37 Participants
Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights \> 20-45 kg and \> 45 kg, through Day 112.
Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the \>= 8-20 kg weight group.
|
Sildenafil Medium Dose
n=49 Participants
Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Sildenafil High Dose
n=68 Participants
Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Combined Sildenafil
n=154 Participants
This includes all subjects in the low, medium and high dose groups.
|
Placebo
n=52 Participants
Subjects randomized to this arm recieved placebo TID (three times daily) for 112 days.
|
|---|---|---|---|---|---|
|
Change From Baseline to Week 16 in Cardiac Index (CI)
|
0.20 liters/minute/meters squared
Standard Deviation 1.17
|
0.02 liters/minute/meters squared
Standard Deviation 1.44
|
0.24 liters/minute/meters squared
Standard Deviation 2.19
|
0.16 liters/minute/meters squared
Standard Deviation 1.76
|
-0.60 liters/minute/meters squared
Standard Deviation 2.12
|
SECONDARY outcome
Timeframe: Baseline, Week 16Population: ITT population, using LOCF (end of treatment) approach for missing data.
RAP was measured using a pressure transducer positioned at the mid-axillary line with the patient in the supine position. Change is observed value at Week 16 minus Baseline value.
Outcome measures
| Measure |
Sildenafil Low Dose
n=39 Participants
Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights \> 20-45 kg and \> 45 kg, through Day 112.
Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the \>= 8-20 kg weight group.
|
Sildenafil Medium Dose
n=55 Participants
Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Sildenafil High Dose
n=71 Participants
Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Combined Sildenafil
n=165 Participants
This includes all subjects in the low, medium and high dose groups.
|
Placebo
n=56 Participants
Subjects randomized to this arm recieved placebo TID (three times daily) for 112 days.
|
|---|---|---|---|---|---|
|
Change From Baseline to Week 16 in Right Atrial Pressure (RAP)
|
7.92 mm Hg
Standard Deviation 2.85
|
8.05 mm Hg
Standard Deviation 4.42
|
7.75 mm Hg
Standard Deviation 4.14
|
7.89 mm Hg
Standard Deviation 3.95
|
8.11 mm Hg
Standard Deviation 3.61
|
SECONDARY outcome
Timeframe: Baseline, Week 16Population: ITT population, includes subjects \>= 5 years with a valid questionnaire available in the subject's first language.
CHQ-PF28: validated generic Quality of Life (QoL) questionnaire for subjects \>= 5 years. Includes 12 domain scores of QoL concepts including physical functioning, social \& school activities, mental health, parent/family concepts. Scores range 0-100: lower scores = lower QoL. Change is observed value at Week 16 minus Baseline value.
Outcome measures
| Measure |
Sildenafil Low Dose
n=31 Participants
Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights \> 20-45 kg and \> 45 kg, through Day 112.
Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the \>= 8-20 kg weight group.
|
Sildenafil Medium Dose
n=29 Participants
Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Sildenafil High Dose
n=43 Participants
Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Combined Sildenafil
n=103 Participants
This includes all subjects in the low, medium and high dose groups.
|
Placebo
n=40 Participants
Subjects randomized to this arm recieved placebo TID (three times daily) for 112 days.
|
|---|---|---|---|---|---|
|
Change From Baseline to Week 16 in Child Health Questionnaire Parent Form (CHQ-PF28), Physical Scale
|
14.0 score on scale
Standard Deviation 13.1
|
9.8 score on scale
Standard Deviation 11.8
|
5.9 score on scale
Standard Deviation 10.5
|
9.4 score on scale
Standard Deviation 12.1
|
8.3 score on scale
Standard Deviation 12.0
|
SECONDARY outcome
Timeframe: Baseline, Week 16Population: ITT population, includes subjects \>= 5years with a valid questionnaire available in the subject's first language.
CHQ-PF28: validated generic Quality of Life (QoL) questionnaire for subjects \>= 5 years. Includes 12 domain scores of QoL concepts including physical functioning, social \& school activities, mental health, parent/family concepts. Scores range 0-100: lower scores = lower QoL. Change is observed value at Week 16 minus Baseline value.
Outcome measures
| Measure |
Sildenafil Low Dose
n=34 Participants
Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights \> 20-45 kg and \> 45 kg, through Day 112.
Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the \>= 8-20 kg weight group.
|
Sildenafil Medium Dose
n=30 Participants
Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Sildenafil High Dose
n=45 Participants
Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Combined Sildenafil
n=109 Participants
This includes all subjects in the low, medium and high dose groups.
|
Placebo
n=41 Participants
Subjects randomized to this arm recieved placebo TID (three times daily) for 112 days.
|
|---|---|---|---|---|---|
|
Change From Baseline to Week 16 in Child Health Questionnaire Parent Form (CHQ-PF28), Psychosocial Scales
|
5.1 score on scale
Standard Deviation 6.9
|
4.1 score on scale
Standard Deviation 8.1
|
4.3 score on scale
Standard Deviation 10.0
|
4.5 score on scale
Standard Deviation 8.6
|
5.6 score on scale
Standard Deviation 10.3
|
SECONDARY outcome
Timeframe: Baseline, Week 16Population: ITT population, LOCF
WHO PH functional class definitions adapted from New York Heart Association Criteria for Functional Capacity and Therapeutic Class Definitions. Class I = PH without resulting limitation of physical activity, Class II = PH resulting in slight limitation of physical activity, Class III = PH resulting in marked limitation of physical activity, Class IV = PH with inability to carry out any physical activity without symptoms. Improved by 1 class = Class 4 to 3, Class 3 to 2, Class 2 to 1. Improved by 2 classes = Class 4 to 2, Class 3 to 1. Change is observed value at Week 16 minus Baseline value.
Outcome measures
| Measure |
Sildenafil Low Dose
n=31 Participants
Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights \> 20-45 kg and \> 45 kg, through Day 112.
Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the \>= 8-20 kg weight group.
|
Sildenafil Medium Dose
n=34 Participants
Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Sildenafil High Dose
n=55 Participants
Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Combined Sildenafil
n=120 Participants
This includes all subjects in the low, medium and high dose groups.
|
Placebo
n=35 Participants
Subjects randomized to this arm recieved placebo TID (three times daily) for 112 days.
|
|---|---|---|---|---|---|
|
Change From Baseline to Week 16 in World Health Organization (WHO) Pulmonary Hypertension (PH) Functional Class
No change
|
25 units
|
24 units
|
38 units
|
84 units
|
31 units
|
|
Change From Baseline to Week 16 in World Health Organization (WHO) Pulmonary Hypertension (PH) Functional Class
Improved by 1 class
|
6 units
|
10 units
|
16 units
|
32 units
|
4 units
|
|
Change From Baseline to Week 16 in World Health Organization (WHO) Pulmonary Hypertension (PH) Functional Class
Improved by 2 classes
|
0 units
|
0 units
|
1 units
|
1 units
|
0 units
|
Adverse Events
Sildenafil Low Dose
Serious events: 1 serious events
Other events: 22 other events
Deaths: 0 deaths
Sildenafil Medium Dose
Serious events: 1 serious events
Other events: 37 other events
Deaths: 0 deaths
Sildenafil High Dose
Serious events: 7 serious events
Other events: 44 other events
Deaths: 0 deaths
Combined Sildenafil
Serious events: 9 serious events
Other events: 102 other events
Deaths: 0 deaths
Placebo
Serious events: 2 serious events
Other events: 29 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Sildenafil Low Dose
Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights \> 20-45 kg and \> 45 kg, through Day 112.
Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the \>= 8-20 kg weight group.
|
Sildenafil Medium Dose
Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Sildenafil High Dose
Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Combined Sildenafil
This includes all subjects in the low, medium and high dose groups.
|
Placebo
Subjects randomized to this arm recieved placebo TID (three times daily) for 112 days.
|
|---|---|---|---|---|---|
|
Cardiac disorders
Bradycardia
|
0.00%
0/42
|
0.00%
0/55
|
1.3%
1/77
|
0.57%
1/174
|
0.00%
0/60
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/42
|
0.00%
0/55
|
1.3%
1/77
|
0.57%
1/174
|
0.00%
0/60
|
|
Cardiac disorders
Cyanosis
|
2.4%
1/42
|
0.00%
0/55
|
0.00%
0/77
|
0.57%
1/174
|
0.00%
0/60
|
|
Cardiac disorders
Ventricular arrhythmia
|
0.00%
0/42
|
0.00%
0/55
|
1.3%
1/77
|
0.57%
1/174
|
0.00%
0/60
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/42
|
0.00%
0/55
|
0.00%
0/77
|
0.00%
0/174
|
1.7%
1/60
|
|
Gastrointestinal disorders
Haematochezia
|
2.4%
1/42
|
0.00%
0/55
|
0.00%
0/77
|
0.57%
1/174
|
0.00%
0/60
|
|
General disorders
Pyrexia
|
0.00%
0/42
|
0.00%
0/55
|
1.3%
1/77
|
0.57%
1/174
|
0.00%
0/60
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/42
|
0.00%
0/55
|
1.3%
1/77
|
0.57%
1/174
|
0.00%
0/60
|
|
Infections and infestations
Pneumonia
|
0.00%
0/42
|
1.8%
1/55
|
2.6%
2/77
|
1.7%
3/174
|
0.00%
0/60
|
|
Infections and infestations
Pneumonia bacterial
|
0.00%
0/42
|
0.00%
0/55
|
0.00%
0/77
|
0.00%
0/174
|
1.7%
1/60
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/42
|
1.8%
1/55
|
1.3%
1/77
|
1.1%
2/174
|
0.00%
0/60
|
|
Nervous system disorders
Syncope
|
2.4%
1/42
|
0.00%
0/55
|
0.00%
0/77
|
0.57%
1/174
|
0.00%
0/60
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.00%
0/42
|
0.00%
0/55
|
1.3%
1/77
|
0.57%
1/174
|
0.00%
0/60
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.4%
1/42
|
0.00%
0/55
|
0.00%
0/77
|
0.57%
1/174
|
0.00%
0/60
|
|
Respiratory, thoracic and mediastinal disorders
Stridor
|
0.00%
0/42
|
0.00%
0/55
|
1.3%
1/77
|
0.57%
1/174
|
0.00%
0/60
|
Other adverse events
| Measure |
Sildenafil Low Dose
Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights \> 20-45 kg and \> 45 kg, through Day 112.
Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the \>= 8-20 kg weight group.
|
Sildenafil Medium Dose
Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Sildenafil High Dose
Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights \>= 8-20 kg, \> 20-45 kg, \> 45 kg respectively, through Day 112
|
Combined Sildenafil
This includes all subjects in the low, medium and high dose groups.
|
Placebo
Subjects randomized to this arm recieved placebo TID (three times daily) for 112 days.
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/42
|
3.6%
2/55
|
0.00%
0/77
|
1.1%
2/174
|
1.7%
1/60
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/42
|
0.00%
0/55
|
2.6%
2/77
|
1.1%
2/174
|
3.3%
2/60
|
|
Gastrointestinal disorders
Abdominal pain
|
2.4%
1/42
|
0.00%
0/55
|
2.6%
2/77
|
1.7%
3/174
|
5.0%
3/60
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/42
|
0.00%
0/55
|
3.9%
3/77
|
1.7%
3/174
|
0.00%
0/60
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/42
|
5.5%
3/55
|
3.9%
3/77
|
3.4%
6/174
|
1.7%
1/60
|
|
Gastrointestinal disorders
Diarrhoea
|
4.8%
2/42
|
5.5%
3/55
|
9.1%
7/77
|
6.9%
12/174
|
6.7%
4/60
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/42
|
3.6%
2/55
|
0.00%
0/77
|
1.1%
2/174
|
1.7%
1/60
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/42
|
7.3%
4/55
|
5.2%
4/77
|
4.6%
8/174
|
0.00%
0/60
|
|
Gastrointestinal disorders
Vomiting
|
7.1%
3/42
|
9.1%
5/55
|
14.3%
11/77
|
10.9%
19/174
|
6.7%
4/60
|
|
General disorders
Chest pain
|
4.8%
2/42
|
1.8%
1/55
|
2.6%
2/77
|
2.9%
5/174
|
3.3%
2/60
|
|
General disorders
Fatigue
|
4.8%
2/42
|
0.00%
0/55
|
2.6%
2/77
|
2.3%
4/174
|
1.7%
1/60
|
|
Infections and infestations
Bronchitis
|
4.8%
2/42
|
9.1%
5/55
|
3.9%
3/77
|
4.6%
8/174
|
1.7%
1/60
|
|
Infections and infestations
Influenza
|
0.00%
0/42
|
3.6%
2/55
|
0.00%
0/77
|
1.1%
2/174
|
0.00%
0/60
|
|
Infections and infestations
Laryngitis
|
2.4%
1/42
|
0.00%
0/55
|
1.3%
1/77
|
1.1%
2/174
|
3.3%
2/60
|
|
Infections and infestations
Nasopharyngitis
|
7.1%
3/42
|
5.5%
3/55
|
2.6%
2/77
|
4.6%
8/174
|
6.7%
4/60
|
|
Infections and infestations
Pharyngitis
|
7.1%
3/42
|
5.5%
3/55
|
1.3%
1/77
|
4.0%
7/174
|
0.00%
0/60
|
|
Infections and infestations
Pneumonia
|
0.00%
0/42
|
3.6%
2/55
|
0.00%
0/77
|
1.1%
2/174
|
0.00%
0/60
|
|
Infections and infestations
Rhinitis
|
2.4%
1/42
|
5.5%
3/55
|
1.3%
1/77
|
2.9%
5/174
|
1.7%
1/60
|
|
Infections and infestations
Upper respiratory tract infection
|
9.5%
4/42
|
14.5%
8/55
|
7.8%
6/77
|
10.3%
18/174
|
6.7%
4/60
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
4.8%
2/42
|
0.00%
0/55
|
0.00%
0/77
|
1.1%
2/174
|
3.3%
2/60
|
|
Nervous system disorders
Dizziness
|
4.8%
2/42
|
3.6%
2/55
|
2.6%
2/77
|
3.4%
6/174
|
3.3%
2/60
|
|
Nervous system disorders
Headache
|
11.9%
5/42
|
10.9%
6/55
|
15.6%
12/77
|
13.2%
23/174
|
13.3%
8/60
|
|
Renal and urinary disorders
Enuresis
|
0.00%
0/42
|
3.6%
2/55
|
0.00%
0/77
|
1.1%
2/174
|
0.00%
0/60
|
|
Reproductive system and breast disorders
Erection increased
|
0.00%
0/42
|
1.8%
1/55
|
2.6%
2/77
|
1.7%
3/174
|
0.00%
0/60
|
|
Reproductive system and breast disorders
Spontaneous penile erection
|
0.00%
0/42
|
3.6%
2/55
|
1.3%
1/77
|
1.7%
3/174
|
0.00%
0/60
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.8%
2/42
|
7.3%
4/55
|
2.6%
2/77
|
4.6%
8/174
|
5.0%
3/60
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
2.4%
1/42
|
3.6%
2/55
|
3.9%
3/77
|
3.4%
6/174
|
3.3%
2/60
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
2.4%
1/42
|
3.6%
2/55
|
0.00%
0/77
|
1.7%
3/174
|
1.7%
1/60
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/42
|
0.00%
0/55
|
0.00%
0/77
|
0.00%
0/174
|
3.3%
2/60
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/42
|
7.3%
4/55
|
2.6%
2/77
|
3.4%
6/174
|
0.00%
0/60
|
|
Skin and subcutaneous tissue disorders
Rash macular
|
0.00%
0/42
|
3.6%
2/55
|
1.3%
1/77
|
1.7%
3/174
|
0.00%
0/60
|
|
Vascular disorders
Flushing
|
2.4%
1/42
|
1.8%
1/55
|
0.00%
0/77
|
1.1%
2/174
|
5.0%
3/60
|
|
General disorders
Pyrexia
|
7.1%
3/42
|
14.5%
8/55
|
10.4%
8/77
|
10.9%
19/174
|
1.7%
1/60
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of \< 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), \< 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER