Trial Outcomes & Findings for Evaluate The Clinical Effectiveness, Safety And Tolerability Of Sildenafil Used In Doses ≥20mg TID For The Treatment Of Pulmonary Arterial Hypertension (NCT NCT01365585)
NCT ID: NCT01365585
Last Updated: 2021-02-01
Results Overview
6MWD was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed.
COMPLETED
227 participants
Baseline, Year 1
2021-02-01
Participant Flow
Participant milestones
| Measure |
Sildenafil
Participants who received sildenafil greater than or equal to 20 milligram (mg) three times daily as per Summary of Product Characteristics (SmPC) for the treatment of pulmonary arterial hypertension (PAH) for a period of at least 3 months, were observed retrospectively for 5 years.
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|---|---|
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Overall Study
STARTED
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227
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Overall Study
COMPLETED
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227
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Evaluate The Clinical Effectiveness, Safety And Tolerability Of Sildenafil Used In Doses ≥20mg TID For The Treatment Of Pulmonary Arterial Hypertension
Baseline characteristics by cohort
| Measure |
Sildenafil
n=227 Participants
Participants who received sildenafil greater than or equal to 20 milligram (mg) three times daily as per Summary of Product Characteristics (SmPC) for the treatment of pulmonary arterial hypertension (PAH) for a period of at least 3 months, were observed retrospectively for 5 years.
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|---|---|
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Age, Continuous
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60.5 years
STANDARD_DEVIATION 14.37 • n=93 Participants
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Sex/Gender, Customized
Female
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145 participants
n=93 Participants
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Sex/Gender, Customized
Male
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81 participants
n=93 Participants
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Six-Minute Walk Distance (6MWD)
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331.7 meter
STANDARD_DEVIATION 117.42 • n=93 Participants
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New York Heart Association, World Health Organization (NYHA/WHO) Functional Class
Class I
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1 participants
n=93 Participants
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New York Heart Association, World Health Organization (NYHA/WHO) Functional Class
Class II
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39 participants
n=93 Participants
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New York Heart Association, World Health Organization (NYHA/WHO) Functional Class
Class III
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163 participants
n=93 Participants
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New York Heart Association, World Health Organization (NYHA/WHO) Functional Class
Class IV
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13 participants
n=93 Participants
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Right Atrial Pressure (RAP)
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6.6 millimeters of mercury (mmHg)
STANDARD_DEVIATION 4.85 • n=93 Participants
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Mean Pulmonary Arterial Pressure (mPAP) at rest
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44.8 mmHg
STANDARD_DEVIATION 12.37 • n=93 Participants
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Pulmonary Vascular Resistance (PVR)
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612.8 dynes*second/centimeter^5
STANDARD_DEVIATION 250.54 • n=93 Participants
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Cardiac Index (CI)
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2.5 (Liter/minute)/square meter([L/min]/m^2)
STANDARD_DEVIATION 1.51 • n=93 Participants
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Pulmonary Capillary Wedge Pressure (PCWP)
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7.6 mmHg
STANDARD_DEVIATION 3.84 • n=93 Participants
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Borg Dyspnea Index
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3.7 units on a scale
STANDARD_DEVIATION 1.91 • n=93 Participants
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PRIMARY outcome
Timeframe: Baseline, Year 1Population: Analysis population included all participants who satisfied the eligibility criteria for the study. Here, 'N' (number of participants analyzed) included those participants who were evaluable for this measure.
6MWD was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed.
Outcome measures
| Measure |
Sildenafil
n=132 Participants
Participants who received sildenafil greater than or equal to 20 milligram (mg) three times daily as per Summary of Product Characteristics (SmPC) for the treatment of pulmonary arterial hypertension (PAH) for a period of at least 3 months, were observed retrospectively for 5 years.
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Change From Baseline in 6-Minute Walk Distance (6MWD) at Year 1
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29.4 meter
Standard Deviation 81.38
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PRIMARY outcome
Timeframe: Baseline, Year 2Population: Analysis population included all participants who satisfied the eligibility criteria for the study. Here, 'N' (number of participants analyzed) included those participants who were evaluable for this measure.
6MWD was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed.
Outcome measures
| Measure |
Sildenafil
n=74 Participants
Participants who received sildenafil greater than or equal to 20 milligram (mg) three times daily as per Summary of Product Characteristics (SmPC) for the treatment of pulmonary arterial hypertension (PAH) for a period of at least 3 months, were observed retrospectively for 5 years.
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|---|---|
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Change From Baseline in 6-Minute Walk Distance (6MWD) at Year 2
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20.8 meter
Standard Deviation 83.82
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PRIMARY outcome
Timeframe: Baseline, Year 3Population: Analysis population included all participants who satisfied the eligibility criteria for the study. Here, 'N' (number of participants analyzed) included those participants who were evaluable for this measure.
6MWD was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed.
Outcome measures
| Measure |
Sildenafil
n=31 Participants
Participants who received sildenafil greater than or equal to 20 milligram (mg) three times daily as per Summary of Product Characteristics (SmPC) for the treatment of pulmonary arterial hypertension (PAH) for a period of at least 3 months, were observed retrospectively for 5 years.
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|---|---|
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Change From Baseline in 6-Minute Walk Distance (6MWD) at Year 3
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8.7 meter
Standard Deviation 73.82
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PRIMARY outcome
Timeframe: Baseline, Year 4Population: Analysis population included all participants who satisfied the eligibility criteria for the study. Here, 'N' (number of participants analyzed) included those participants who were evaluable for this measure.
6MWD was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed.
Outcome measures
| Measure |
Sildenafil
n=9 Participants
Participants who received sildenafil greater than or equal to 20 milligram (mg) three times daily as per Summary of Product Characteristics (SmPC) for the treatment of pulmonary arterial hypertension (PAH) for a period of at least 3 months, were observed retrospectively for 5 years.
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|---|---|
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Change From Baseline in 6-Minute Walk Distance (6MWD) at Year 4
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-50.2 meter
Standard Deviation 86.24
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SECONDARY outcome
Timeframe: Baseline, Year 1, 2, 3, 4Population: Analysis population included all participants who satisfied the eligibility criteria for the study. Here, 'N' (number of participants analyzed) included those participants who were evaluable for this measure. Here, 'n' included those participants who were evaluable for this measure at specified time points.
NYHA/WHO functional classification for PAH range from Class I (no limitation in physical activity, no dyspnea with normal activity) to Class IV (can not perform a physical activity without any symptoms, dyspnea at rest). Improvement=reduction in functional class, deterioration = increase in functional class, no change = no change in functional class. Number of participants in each functional class was reported.
Outcome measures
| Measure |
Sildenafil
n=214 Participants
Participants who received sildenafil greater than or equal to 20 milligram (mg) three times daily as per Summary of Product Characteristics (SmPC) for the treatment of pulmonary arterial hypertension (PAH) for a period of at least 3 months, were observed retrospectively for 5 years.
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Change From Baseline in New York Heart Association, World Health Organization (NYHA/WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Year 1, 2, 3 and 4
Year 1: Improved >1 class (n=214)
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3 participants
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Change From Baseline in New York Heart Association, World Health Organization (NYHA/WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Year 1, 2, 3 and 4
Year 1: Improved 1 class (n=214)
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36 participants
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Change From Baseline in New York Heart Association, World Health Organization (NYHA/WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Year 1, 2, 3 and 4
Year 1: No change (n=214)
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140 participants
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Change From Baseline in New York Heart Association, World Health Organization (NYHA/WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Year 1, 2, 3 and 4
Year 1: Worsened 1 class (n=214)
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12 participants
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Change From Baseline in New York Heart Association, World Health Organization (NYHA/WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Year 1, 2, 3 and 4
Year 1: Worsened >1 class (n=214)
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5 participants
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Change From Baseline in New York Heart Association, World Health Organization (NYHA/WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Year 1, 2, 3 and 4
Year 2: Improved >1 class (n=156)
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1 participants
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Change From Baseline in New York Heart Association, World Health Organization (NYHA/WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Year 1, 2, 3 and 4
Year 2: Improved 1 class (n=156)
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27 participants
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Change From Baseline in New York Heart Association, World Health Organization (NYHA/WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Year 1, 2, 3 and 4
Year 2: No change (n=156)
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100 participants
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Change From Baseline in New York Heart Association, World Health Organization (NYHA/WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Year 1, 2, 3 and 4
Year 2: Worsened 1 class (n=156)
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7 participants
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Change From Baseline in New York Heart Association, World Health Organization (NYHA/WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Year 1, 2, 3 and 4
Year 2: Worsened >1 class (n=156)
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4 participants
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Change From Baseline in New York Heart Association, World Health Organization (NYHA/WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Year 1, 2, 3 and 4
Year 3: Improved >1 class (n=88)
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1 participants
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Change From Baseline in New York Heart Association, World Health Organization (NYHA/WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Year 1, 2, 3 and 4
Year 3: Improved 1 class (n=88)
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12 participants
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Change From Baseline in New York Heart Association, World Health Organization (NYHA/WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Year 1, 2, 3 and 4
Year 3: No change (n=88)
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57 participants
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Change From Baseline in New York Heart Association, World Health Organization (NYHA/WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Year 1, 2, 3 and 4
Year 3: Worsened 1 class (n=88)
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7 participants
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Change From Baseline in New York Heart Association, World Health Organization (NYHA/WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Year 1, 2, 3 and 4
Year 3: Worsened >1 class (n=88)
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0 participants
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Change From Baseline in New York Heart Association, World Health Organization (NYHA/WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Year 1, 2, 3 and 4
Year 4: Improved >1 class (n=45)
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0 participants
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Change From Baseline in New York Heart Association, World Health Organization (NYHA/WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Year 1, 2, 3 and 4
Year 4: Improved 1 class (n=45)
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6 participants
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Change From Baseline in New York Heart Association, World Health Organization (NYHA/WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Year 1, 2, 3 and 4
Year 4: No change (n=45)
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27 participants
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Change From Baseline in New York Heart Association, World Health Organization (NYHA/WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Year 1, 2, 3 and 4
Year 4: Worsened 1 class (n=45)
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2 participants
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Change From Baseline in New York Heart Association, World Health Organization (NYHA/WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Year 1, 2, 3 and 4
Year 4: Worsened >1 class (n=45)
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0 participants
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SECONDARY outcome
Timeframe: Baseline, Year 1, 2, 3, 4Population: Data was not summarized because results were available for very few participants and were insufficient for analysis.
RAP was measured using a pressure transducer positioned at the mid-axillary line with the participant in the supine position.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Year 1, 2, 3, 4Population: Data was not summarized because results were available for very few participants and were insufficient for analysis.
mPAP was measured using a pressure transducer positioned at the mid-axillary line with the participant in the supine position.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Year 1, 2, 3, 4Population: Data was not summarized because results were available for very few participants and were insufficient for analysis.
PVR: calculated by subtracting PCWP from mPAP and dividing by cardiac output in pulmonary circulation (COpulm).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Year 1, 2, 3, 4Population: Data was not summarized because results were available for very few participants and were insufficient for analysis.
CI: calculated as COsys divided by BSA.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Year 1, 2, 3, 4Population: Data was not summarized because results were available for very few participants and were insufficient for analysis.
PCWP was measured by pulmonary artery catheterization and provided an indirect measure of left atrial pressure.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Year 1, 2, 3, 4Population: Analysis population included all participants who satisfied the eligibility criteria for the study. Here, 'N' (number of participants analyzed) included those participants who were evaluable for this measure. 'n' included those participants who were evaluable for this measure at specified time points.
Borg dyspnea scale: 10-point scale where following scores stands for severity of dyspnea: 0=no breathlessness at all;0.5=very very slight (just noticeable); 1=very slight; 2=slight breathlessness; 3=moderate; 4=some what severe; 5=severe; 7=very severe breathlessness; 9=very very severe (almost maximum) and 10=maximum.
Outcome measures
| Measure |
Sildenafil
n=118 Participants
Participants who received sildenafil greater than or equal to 20 milligram (mg) three times daily as per Summary of Product Characteristics (SmPC) for the treatment of pulmonary arterial hypertension (PAH) for a period of at least 3 months, were observed retrospectively for 5 years.
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|---|---|
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Change From Baseline in Borg Dyspnea Index at Year 1, 2, 3 and 4
Change at Year 1 (n=118)
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-0.4 units on a scale
Standard Deviation 1.88
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Change From Baseline in Borg Dyspnea Index at Year 1, 2, 3 and 4
Change at Year 2 (n=65)
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0.0 units on a scale
Standard Deviation 2.01
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Change From Baseline in Borg Dyspnea Index at Year 1, 2, 3 and 4
Change at Year 3 (n=27)
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0.3 units on a scale
Standard Deviation 1.82
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Change From Baseline in Borg Dyspnea Index at Year 1, 2, 3 and 4
Change at Year 4 (n=8)
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0.4 units on a scale
Standard Deviation 1.92
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Adverse Events
Sildenafil
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Sildenafil
n=227 participants at risk
Participants who received sildenafil greater than or equal to 20 milligram (mg) three times daily as per Summary of Product Characteristics (SmPC) for the treatment of pulmonary arterial hypertension (PAH) for a period of at least 3 months, were observed retrospectively for 5 years.
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|---|---|
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General disorders
Ankle oedema, facial flushing
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0.44%
1/227
Only those adverse events that were determined to be related to sildenafil by the investigator were reported in this observational retrospective study.
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General disorders
Back pain or dizziness or eyesight
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0.44%
1/227
Only those adverse events that were determined to be related to sildenafil by the investigator were reported in this observational retrospective study.
|
|
General disorders
Cough
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0.44%
1/227
Only those adverse events that were determined to be related to sildenafil by the investigator were reported in this observational retrospective study.
|
|
General disorders
Dizziness
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0.44%
1/227
Only those adverse events that were determined to be related to sildenafil by the investigator were reported in this observational retrospective study.
|
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General disorders
Gastro-intestinal symptoms
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0.44%
1/227
Only those adverse events that were determined to be related to sildenafil by the investigator were reported in this observational retrospective study.
|
|
General disorders
Head fuzzy/mild headache/mild flushing/mild nasal congestion
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0.44%
1/227
Only those adverse events that were determined to be related to sildenafil by the investigator were reported in this observational retrospective study.
|
|
General disorders
Headache, diarrhoea and anxiety
|
0.44%
1/227
Only those adverse events that were determined to be related to sildenafil by the investigator were reported in this observational retrospective study.
|
|
General disorders
Mild headache/increased heart rate
|
0.44%
1/227
Only those adverse events that were determined to be related to sildenafil by the investigator were reported in this observational retrospective study.
|
|
General disorders
Nasal stuffiness/headache
|
0.44%
1/227
Only those adverse events that were determined to be related to sildenafil by the investigator were reported in this observational retrospective study.
|
|
General disorders
Nose bleeds
|
0.44%
1/227
Only those adverse events that were determined to be related to sildenafil by the investigator were reported in this observational retrospective study.
|
|
General disorders
Rash/itch (severe)
|
0.44%
1/227
Only those adverse events that were determined to be related to sildenafil by the investigator were reported in this observational retrospective study.
|
|
General disorders
Red face/peripheral oedema
|
0.44%
1/227
Only those adverse events that were determined to be related to sildenafil by the investigator were reported in this observational retrospective study.
|
|
General disorders
Vague upper abdominal discomfort by suspected pancreatic cancer
|
0.44%
1/227
Only those adverse events that were determined to be related to sildenafil by the investigator were reported in this observational retrospective study.
|
|
General disorders
Worsening of PAH
|
0.44%
1/227
Only those adverse events that were determined to be related to sildenafil by the investigator were reported in this observational retrospective study.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER