Trial Outcomes & Findings for Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis (NCT NCT00517933)

NCT ID: NCT00517933

Last Updated: 2015-06-24

Results Overview

This is a binary score (1 or 0) with 1 being better than 0. All models adjust for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 180 participants
• Primary outcome timeframe: Measured at Week 12
• Results posted on: 2015-06-24

Participant Flow

Participant milestones

Measure	Sildenafil / Sildenafil 20 mg oral sildenafil 3 times per day	Placebo / Sildenafil 20 mg oral placebo 3 times per day
Period 1 STARTED	89	91
Period 1 COMPLETED	81	85
Period 1 NOT COMPLETED	8	6
Period 2 STARTED	79	83
Period 2 COMPLETED	73	70
Period 2 NOT COMPLETED	6	13

Reasons for withdrawal

Measure	Sildenafil / Sildenafil 20 mg oral sildenafil 3 times per day	Placebo / Sildenafil 20 mg oral placebo 3 times per day
Period 1 Death	2	1
Period 1 Adverse Event	4	4
Period 1 Lost to Follow-up	2	0
Period 1 Underwent lung transplant	0	1
Period 2 Death	2	4
Period 2 Adverse Event	2	4
Period 2 Physician Decision	1	0
Period 2 Withdrawal by Subject	1	3
Period 2 Underwent lung transplant	0	2

Baseline Characteristics

Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis

Baseline characteristics by cohort

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for 12 weeks	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks	Total n=180 Participants Total of all reporting groups
Age, Continuous	69.8 years STANDARD_DEVIATION 8.7 • n=5 Participants	68.2 years STANDARD_DEVIATION 9.3 • n=7 Participants	69.0 years STANDARD_DEVIATION 8.9 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	16 Participants n=7 Participants	30 Participants n=5 Participants
Sex: Female, Male Male	75 Participants n=5 Participants	75 Participants n=7 Participants	150 Participants n=5 Participants
Region of Enrollment United States	89 participants n=5 Participants	91 participants n=7 Participants	180 participants n=5 Participants

PRIMARY outcome

Timeframe: Measured at Week 12

This is a binary score (1 or 0) with 1 being better than 0. All models adjust for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
Change in 6-minute Walk Distance From Enrollment to Week 12 (≥ 20% Improvement)	9 participants	6 participants

SECONDARY outcome

Timeframe: Baseline, 6 week, 12 week

The 6MWT measures the distance that a participant can walk in a period of 6 minutes.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
6-minute Walk Distance (6MWT) 1st baseline	246.93 meters Standard Deviation 99.11	267.71 meters Standard Deviation 127.75
6-minute Walk Distance (6MWT) 2nd baseline	246.39 meters Standard Deviation 103.40	269.55 meters Standard Deviation 129.83
6-minute Walk Distance (6MWT) 6 week	237.29 meters Standard Deviation 121.48	257.55 meters Standard Deviation 139.44
6-minute Walk Distance (6MWT) 12 week	239.09 meters Standard Deviation 126.39	249.48 meters Standard Deviation 138.46

SECONDARY outcome

Timeframe: Baseline, week 12

The 6MWT measures the distance that a participant can walk in a period of 6 minutes. All models adjust for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
Estimated Change From Baseline to 12 Weeks in 6-minute Walk Distance	-28.5 meters Interval -43.2 to -13.8	-45.2 meters Interval -59.7 to -30.8

SECONDARY outcome

Timeframe: Week 12

Population: ITT population

The 6MWT was stopped when the pulse oximetry (SpO2) dropped to below 80% for six consecutive seconds. The estimates are based on the Kaplan-Meier event curves with minutes walked as the x-axis.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
Desaturation During 6-minute Walk Test (6MWT)	83.6 percentage of participants Interval 74.4 to 91.0	75.3 percentage of participants Interval 65.3 to 84.3

SECONDARY outcome

Timeframe: Measured from enrollment to 12 weeks (phase I)

The University of California at San Diego Shortness of Breath Questionnaire (SOBQ) uses a 6-point scale (0 = "not at all" to 5 = "maximal or unable to do because of breathlessness") to rate 24 items. The final score ranges from 0 to 120 -- lower scores are better.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
Change in Dyspnea	0.22 units on a scale Interval -3.1 to 3.54	6.81 units on a scale Interval 3.53 to 10.08

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 12 weeks

The University of California at San Diego Shortness of Breath Questionnaire (SOBQ) uses a 6-point scale (0 = "not at all" to 5 = "maximal or unable to do because of breathlessness") to rate 24 items. The final score ranges from 0 to 120 -- lower scores are better. (Raw scores)

Values adjusted for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
University of California at San Diego (UCSD) Shortness of Breath Questionnaire Total 6 week	49.67 units on a scale Standard Deviation 22.74	47.64 units on a scale Standard Deviation 25.61
University of California at San Diego (UCSD) Shortness of Breath Questionnaire Total Baseline	50.71 units on a scale Standard Deviation 22.00	43.28 units on a scale Standard Deviation 20.18
University of California at San Diego (UCSD) Shortness of Breath Questionnaire Total 12 Week	50.58 units on a scale Standard Deviation 23.41	48.13 units on a scale Standard Deviation 24.10
University of California at San Diego (UCSD) Shortness of Breath Questionnaire Total Change from Baseline to 6 weeks	-1.27 units on a scale Standard Deviation 12.63	4.42 units on a scale Standard Deviation 17.16
University of California at San Diego (UCSD) Shortness of Breath Questionnaire Total Change from Baseline to 12 weeks	0.30 units on a scale Standard Deviation 16.01	6.99 units on a scale Standard Deviation 18.43

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: ITT

Change in FVC (liters) from baseline (time 0) to week 12 comparing the sildenafil and placebo groups. Values adjusted for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
Change in Forced Vital Capacity (FVC) Adjusted Values	-0.04 liters Interval -0.09 to 0.0	-0.05 liters Interval -0.1 to -0.01

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: ITT

Raw scores of FVC (liters) from baseline (time 0) to week 6 and 12 comparing the sildenafil and placebo groups

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
Forced Vital Capacity (FVC) Change from baseline to 12 weeks	-0.04 liters Standard Deviation 0.23	-0.05 liters Standard Deviation 0.20
Forced Vital Capacity (FVC) Baseline	2.25 liters Standard Deviation 0.70	2.42 liters Standard Deviation 0.75
Forced Vital Capacity (FVC) Week 6	2.25 liters Standard Deviation 0.72	2.40 liters Standard Deviation 0.74
Forced Vital Capacity (FVC) Week 12	2.22 liters Standard Deviation 0.75	2.36 liters Standard Deviation 0.78
Forced Vital Capacity (FVC) Change from baseline to 6 weeks	-0.03 liters Standard Deviation 0.21	-0.03 liters Standard Deviation 0.15

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: ITT

Change in DLCO (% predicted) measured at baseline (time 0), and week 12 comparing the sildenafil and placebo groups. All models adjust for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
Change in Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) Adjusted Values	-0.30 percentage of predicted (DLCO) Interval -1.4 to 0.7	-1.9 percentage of predicted (DLCO) Interval -2.9 to -0.8

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: ITT

Raw scores of DLCO (% predicted) measured at baseline (time 0), week 6, and week 12 comparing the sildenafil and placebo groups

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) Baseline	25.81 percentage of predicted (DLCO) Standard Deviation 6.03	26.73 percentage of predicted (DLCO) Standard Deviation 6.16
Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) Week 6	26.00 percentage of predicted (DLCO) Standard Deviation 7.05	26.11 percentage of predicted (DLCO) Standard Deviation 6.28
Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) Week 12	25.66 percentage of predicted (DLCO) Standard Deviation 6.79	25.38 percentage of predicted (DLCO) Standard Deviation 7.43
Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) Change from baseline to 6 weeks	-0.07 percentage of predicted (DLCO) Standard Deviation 4.35	-1.15 percentage of predicted (DLCO) Standard Deviation 4.59
Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) Change from baseline to 12 weeks	-0.33 percentage of predicted (DLCO) Standard Deviation 4.58	-1.78 percentage of predicted (DLCO) Standard Deviation 6.32

SECONDARY outcome

Timeframe: Baseline, 12 week

The BDI was calculated by using a 10-point scale (0 = None, 10 = Maximum) and indicates the degree of breathlessness after completion of the 6-minute walk test. Values adjusted for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
Change in Borg Dyspnea Index (BDI) After 6 Minute Walk Test (Adjusted Values)	0.04 units on a scale Interval -0.3 to 0.37	0.37 units on a scale Interval 0.04 to 0.7

SECONDARY outcome

Timeframe: Baseline, 6 week, 12 week

The BDI was calculated by using a 10-point scale (0 = None, 10 = Maximum) and indicates the degree of breathlessness after completion of the 6-minute walk test.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
Borg Dyspnea Index (BDI) After 6 Minute Walk Test (Raw Scores) Baseline	3.72 units on a scale Standard Deviation 1.79	3.23 units on a scale Standard Deviation 1.80
Borg Dyspnea Index (BDI) After 6 Minute Walk Test (Raw Scores) 6 week	3.53 units on a scale Standard Deviation 1.91	3.42 units on a scale Standard Deviation 1.79
Borg Dyspnea Index (BDI) After 6 Minute Walk Test (Raw Scores) 12 week	3.76 units on a scale Standard Deviation 2.22	3.49 units on a scale Standard Deviation 1.61
Borg Dyspnea Index (BDI) After 6 Minute Walk Test (Raw Scores) Change from Baseline to 6 week	-0.23 units on a scale Standard Deviation 1.37	0.37 units on a scale Standard Deviation 1.42
Borg Dyspnea Index (BDI) After 6 Minute Walk Test (Raw Scores) Change from Baseline to 12 week	0.09 units on a scale Standard Deviation 1.62	0.39 units on a scale Standard Deviation 1.70

SECONDARY outcome

Timeframe: Baseline, 12 week

The St. George's Respiratory Questionnaire asks patients how breathing problems impair their life and is scored from 0 (no impairment) to 100 (maximum impairment.) Values adjusted for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
Change in St. George's Respiratory Questionnaire (Total Score) (Adjusted Values)	-1.6 units on a scale Interval -3.9 to 0.6	2.5 units on a scale Interval 0.2 to 4.7

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 12 weeks

Mean raw scores of the St. George's Respiratory Questionnaire. The St. George's Respiratory Questionnaire asks patients how breathing problems impair their life and is scored from 0 (no impairment) to 100 (maximum impairment.)

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
St. George's Respiratory Questionnaire (Total Score) 6 week	52.56 units on a scale Standard Deviation 16.81	51.74 units on a scale Standard Deviation 16.45
St. George's Respiratory Questionnaire (Total Score) 12 Week	52.58 units on a scale Standard Deviation 16.35	52.19 units on a scale Standard Deviation 16.26
St. George's Respiratory Questionnaire (Total Score) Baseline	54.55 units on a scale Standard Deviation 16.46	51.72 units on a scale Standard Deviation 15.86
St. George's Respiratory Questionnaire (Total Score) Change from Baseline to 6 weeks	-1.45 units on a scale Standard Deviation 10.11	1.65 units on a scale Standard Deviation 10.53
St. George's Respiratory Questionnaire (Total Score) Change from Baseline to 12 weeks	-1.71 units on a scale Standard Deviation 12.35	2.88 units on a scale Standard Deviation 10.61

SECONDARY outcome

Timeframe: Baseline, 12 weeks

The St. George's Respiratory Questionnaire asks patients how breathing problems impair their life and is scored from 0 (no impairment) to 100 (maximum impairment). Values adjusted for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
Change in St. George's Respiratory Questionnaire (Symptoms Score) Adjusted Value	-3.6 units on a scale Interval -7.0 to -0.1	2.2 units on a scale Interval -1.3 to 5.6

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 12 weeks

The St. George's Respiratory Questionnaire asks patients how breathing problems impair their life and is scored from 0 (no impairment) to 100 (maximum impairment). Mean raw scores of the St. George's Respiratory Questionnaire. Mean raw scores of the St. George's Respiratory Questionnaire.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
St. George's Respiratory Questionnaire (Symptoms Score) 6 week	55.89 units on a scale Standard Deviation 17.72	56.26 units on a scale Standard Deviation 18.77
St. George's Respiratory Questionnaire (Symptoms Score) Baseline	58.20 units on a scale Standard Deviation 17.75	53.99 units on a scale Standard Deviation 18.90
St. George's Respiratory Questionnaire (Symptoms Score) 12 Week	54.49 units on a scale Standard Deviation 17.59	55.55 units on a scale Standard Deviation 19.08
St. George's Respiratory Questionnaire (Symptoms Score) Change from Baseline to 6 weeks	-2.05 units on a scale Standard Deviation 16.72	3.15 units on a scale Standard Deviation 16.30
St. George's Respiratory Questionnaire (Symptoms Score) Change from Baseline to 12 weeks	-3.57 units on a scale Standard Deviation 17.95	2.80 units on a scale Standard Deviation 14.74

SECONDARY outcome

Timeframe: Baseline, 12 weeks

The St. George's Respiratory Questionnaire asks patients how breathing problems impair their life and is scored from 0 (no impairment) to 100 (maximum impairment). Values adjusted for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
Change in St. George's Respiratory Questionnaire (Activity Score) Adjusted Value	-1.2 units on a scale Interval -3.7 to 1.4	2.5 units on a scale Interval 0.0 to 5.0

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 12 weeks

The St. George's Respiratory Questionnaire asks patients how breathing problems impair their life and is scored from 0 (no impairment) to 100 (maximum impairment). Mean raw scores of the St. George's Respiratory Questionnaire.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
St. George's Respiratory Questionnaire (Activity Score) 6 week	69.95 units on a scale Standard Deviation 18.66	67.44 units on a scale Standard Deviation 18.51
St. George's Respiratory Questionnaire (Activity Score) 12 Week	69.75 units on a scale Standard Deviation 18.63	69.13 units on a scale Standard Deviation 19.34
St. George's Respiratory Questionnaire (Activity Score) Change from Baseline to 12 weeks	-1.25 units on a scale Standard Deviation 12.56	2.77 units on a scale Standard Deviation 13.27
St. George's Respiratory Questionnaire (Activity Score) Baseline	71.20 units on a scale Standard Deviation 17.50	68.02 units on a scale Standard Deviation 17.63
St. George's Respiratory Questionnaire (Activity Score) Change from Baseline to 6 weeks	-1.95 units on a scale Standard Deviation 10.82	0.28 units on a scale Standard Deviation 10.87

SECONDARY outcome

Timeframe: Baseline, 12 weeks

The St. George's Respiratory Questionnaire asks patients how breathing problems impair their life and is scored from 0 (no impairment) to 100 (maximum impairment). Values adjusted for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
Change in St. George's Respiratory Questionnaire (Impacts Score) Adjusted Value	-0.9 units on a scale Interval -3.8 to 2.0	2.8 units on a scale Interval 0.0 to 5.7

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 12 weeks

The St. George's Respiratory Questionnaire asks patients how breathing problems impair their life and is scored from 0 (no impairment) to 100 (maximum impairment). Mean raw scores of the St. George's Respiratory Questionnaire.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
St. George's Respiratory Questionnaire (Impacts Score) Baseline	43.20 units on a scale Standard Deviation 19.26	39.77 units on a scale Standard Deviation 18.81
St. George's Respiratory Questionnaire (Impacts Score) 6 week	41.62 units on a scale Standard Deviation 19.49	41.58 units on a scale Standard Deviation 19.68
St. George's Respiratory Questionnaire (Impacts Score) 12 Week	41.95 units on a scale Standard Deviation 19.23	41.05 units on a scale Standard Deviation 18.81
St. George's Respiratory Questionnaire (Impacts Score) Change from Baseline to 6 weeks	-0.67 units on a scale Standard Deviation 12.79	2.37 units on a scale Standard Deviation 12.94
St. George's Respiratory Questionnaire (Impacts Score) Change from Baseline to 12 weeks	-0.91 units on a scale Standard Deviation 15.90	3.15 units on a scale Standard Deviation 13.11

SECONDARY outcome

Timeframe: Baseline, 12 weeks

The ICEpop CAPability measure for Older people (ICECAP-O) is a measure of capability in older people for use in economic evaluation. The values of ICECAP-O range from 0 (worst) to 1 (best).

Values adjusted for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
Change in ICECAP-O Adjusted Value	0.00 units on a scale Interval -0.02 to 0.03	-0.02 units on a scale Interval -0.04 to 0.0

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 12 weeks

The ICEpop CAPability measure for Older people (ICECAP-O) is a measure of capability in older people for use in economic evaluation. The values of ICECAP-O range from 0 (worst) to 1 (best). Mean raw scores of ICECAP-O.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
ICECAP-O Baseline	0.79 units on a scale Standard Deviation 0.14	0.81 units on a scale Standard Deviation 0.13
ICECAP-O 6 week	0.80 units on a scale Standard Deviation 0.16	0.76 units on a scale Standard Deviation 0.17
ICECAP-O 12 Week	0.79 units on a scale Standard Deviation 0.14	0.81 units on a scale Standard Deviation 0.14
ICECAP-O Change from Baseline to 6 weeks	0.02 units on a scale Standard Deviation 0.12	-0.05 units on a scale Standard Deviation 0.12
ICECAP-O Change from Baseline to 12 weeks	0.00 units on a scale Standard Deviation 0.11	-0.02 units on a scale Standard Deviation 0.10

SECONDARY outcome

Timeframe: Baseline, 12 weeks

The thermometer score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). Higher scores indicate a better health state.

Values adjusted for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
Change in EuroQOL Thermometer (Adjusted Value)	0.5 units on a scale Interval -3.1 to 4.1	-1.8 units on a scale Interval -5.3 to 1.7

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 12 weeks

The thermometer score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). Higher scores indicate a better health state.

Mean raw scores of EuroQOL Thermometer.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
EuroQOL Thermometer Baseline	66.49 units on a scale Standard Deviation 17.45	67.66 units on a scale Standard Deviation 16.98
EuroQOL Thermometer 6 week	69.47 units on a scale Standard Deviation 16.92	67.09 units on a scale Standard Deviation 19.65
EuroQOL Thermometer 12 Week	66.96 units on a scale Standard Deviation 16.45	67.05 units on a scale Standard Deviation 16.37
EuroQOL Thermometer Change from Baseline to 6 weeks	2.51 units on a scale Standard Deviation 15.32	-1.40 units on a scale Standard Deviation 17.23
EuroQOL Thermometer Change from Baseline to 12 weeks	0.49 units on a scale Standard Deviation 17.28	-2.12 units on a scale Standard Deviation 19.08

SECONDARY outcome

Timeframe: Baseline, 12 weeks

EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (eg, "confined to bed"). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in total score range -0.594 to 1.000; higher score indicates better health state.

Values adjusted for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
Change in EuroQOL (EQ-5D) Utility - Adjusted Value	-0.01 units on a scale Interval -0.06 to 0.03	-0.03 units on a scale Interval -0.08 to 0.01

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 12 weeks

EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (eg, "confined to bed"). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in total score range -0.594 to 1.000; higher score indicates better health state.

Mean raw scores of EuroQOL Utility.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
EuroQOL (EQ-5D) Utility Baseline	0.71 units on a scale Standard Deviation 0.24	0.74 units on a scale Standard Deviation 0.19
EuroQOL (EQ-5D) Utility 6 week	0.75 units on a scale Standard Deviation 0.23	0.71 units on a scale Standard Deviation 0.25
EuroQOL (EQ-5D) Utility 12 Week	0.70 units on a scale Standard Deviation 0.26	0.72 units on a scale Standard Deviation 0.21
EuroQOL (EQ-5D) Utility Change from Baseline to 6 weeks	0.04 units on a scale Standard Deviation 0.18	-0.02 units on a scale Standard Deviation 0.24
EuroQOL (EQ-5D) Utility Change from Baseline to 12 weeks	-0.01 units on a scale Standard Deviation 0.23	-0.03 units on a scale Standard Deviation 0.19

SECONDARY outcome

Timeframe: Baseline, 12 weeks

The SF36 measures functional health and well-being scores on eight scales that correlate with two aggregate scores.

Each score ranges from 0 to 100, with a higher score indicating better function.

Values adjusted for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
Change in Short Form Health Survey (SF36) General Health - Adjusted Value	-1.0 units on a scale Interval -2.5 to 0.4	-3.9 units on a scale Interval -5.4 to -2.4

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 12 weeks

The SF36 measures functional health and well-being scores on eight scales that correlate with two aggregate scores.

Each score ranges from 0 to 100, with a higher score indicating better function.

Mean raw scores of SF36 General Health

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
Short Form Health Survey (SF36) General Health Baseline	36.99 units on a scale Standard Deviation 9.64	37.66 units on a scale Standard Deviation 8.73
Short Form Health Survey (SF36) General Health 6 week	36.00 units on a scale Standard Deviation 9.85	34.97 units on a scale Standard Deviation 8.64
Short Form Health Survey (SF36) General Health 12 Week	36.31 units on a scale Standard Deviation 8.91	34.39 units on a scale Standard Deviation 8.41

SECONDARY outcome

Timeframe: Baseline, 12 weeks

The SF36 measures functional health and well-being scores on eight scales that correlate with two aggregate scores.

Each score ranges from 0 to 100, with a higher score indicating better function.

Values adjusted for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
Change in SF36 Aggregate Physical (Adjusted Value)	-0.5 units on a scale Interval -1.9 to 0.8	-0.4 units on a scale Interval -1.7 to 1.0

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 12 weeks

The SF36 measures functional health and well-being scores on eight scales that correlate with two aggregate scores.

Each score ranges from 0 to 100, with a higher score indicating better function.

Mean raw scores of SF36 Aggregate Physical.

Outcome measures

Measure	Sildenafil n=89 Participants 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for an additional 12 weeks.	Placebo n=91 Participants 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
Short Form Health Survey (SF36) Aggregate Physical Baseline	-1.68 units on a scale Standard Deviation 0.92	-1.52 units on a scale Standard Deviation 0.87
Short Form Health Survey (SF36) Aggregate Physical 6 week	-1.70 units on a scale Standard Deviation 0.99	-1.58 units on a scale Standard Deviation 0.91
Short Form Health Survey (SF36) Aggregate Physical 12 Week	-1.71 units on a scale Standard Deviation 0.86	-1.51 units on a scale Standard Deviation 0.89
Short Form Health Survey (SF36) Aggregate Physical Change from Baseline to week 6	-0.06 units on a scale Standard Deviation 0.52	-0.08 units on a scale Standard Deviation 0.64
Short Form Health Survey (SF36) Aggregate Physical Change from Baseline to week 12	-0.05 units on a scale Standard Deviation 0.56	-0.05 units on a scale Standard Deviation 0.63

Adverse Events

Sildenafil

Serious events: 13 serious events

Other events: 72 other events

Deaths: 0 deaths

Placebo

Serious events: 15 serious events

Other events: 62 other events

Deaths: 0 deaths

Serious adverse events

Measure	Sildenafil n=89 participants at risk 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for 12 weeks	Placebo n=91 participants at risk 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic, or mediastinal disorder	7.9% 7/89 • Number of events 7	9.9% 9/91 • Number of events 11
Infections and infestations Infection or infestation	3.4% 3/89 • Number of events 4	2.2% 2/91 • Number of events 2
Cardiac disorders Cardiac disorder	1.1% 1/89 • Number of events 1	3.3% 3/91 • Number of events 3
Gastrointestinal disorders GI disorder	2.2% 2/89 • Number of events 2	1.1% 1/91 • Number of events 1
Respiratory, thoracic and mediastinal disorders Idiopathic pulmonary fibrosis	2.2% 2/89 • Number of events 2	5.5% 5/91 • Number of events 5
Respiratory, thoracic and mediastinal disorders Dyspnea	2.2% 2/89 • Number of events 2	1.1% 1/91 • Number of events 1
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.1% 1/89 • Number of events 1	2.2% 2/91 • Number of events 2
Respiratory, thoracic and mediastinal disorders COPD	0.00% 0/89	1.1% 1/91 • Number of events 1
Respiratory, thoracic and mediastinal disorders Hypoxia	1.1% 1/89 • Number of events 1	0.00% 0/91
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/89	1.1% 1/91 • Number of events 1
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/89	1.1% 1/91 • Number of events 1
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.1% 1/89 • Number of events 1	0.00% 0/91
Infections and infestations Pneumonia	2.2% 2/89 • Number of events 2	1.1% 1/91 • Number of events 1
Infections and infestations Bronchitis	0.00% 0/89	1.1% 1/91 • Number of events 1
Infections and infestations Influenza	1.1% 1/89 • Number of events 1	0.00% 0/91
Infections and infestations Viral infection	1.1% 1/89 • Number of events 1	0.00% 0/91
Cardiac disorders Atrial fibrillation	0.00% 0/89	2.2% 2/91 • Number of events 2
Cardiac disorders Cardiac failure congestive	1.1% 1/89 • Number of events 1	0.00% 0/91
Cardiac disorders Coronary artery disease	0.00% 0/89	1.1% 1/91 • Number of events 1
Gastrointestinal disorders Colitis ischemic	1.1% 1/89 • Number of events 1	0.00% 0/91
Gastrointestinal disorders Intestinal obstruction	0.00% 0/89	1.1% 1/91 • Number of events 1
Gastrointestinal disorders Peptic ulcer hemorrhage	1.1% 1/89 • Number of events 1	0.00% 0/91
Hepatobiliary disorders Biliary colic	0.00% 0/89	1.1% 1/91 • Number of events 1
Injury, poisoning and procedural complications Fall	0.00% 0/89	1.1% 1/91 • Number of events 1
Injury, poisoning and procedural complications Femur fracture	0.00% 0/89	1.1% 1/91 • Number of events 1
Injury, poisoning and procedural complications Joint injury	0.00% 0/89	1.1% 1/91 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	0.00% 0/89	1.1% 1/91 • Number of events 1
Nervous system disorders Convulsion	0.00% 0/89	1.1% 1/91 • Number of events 1

Other adverse events

Measure	Sildenafil n=89 participants at risk 20 mg of oral sildenafil 3 times per day for 12 weeks, followed by 20 mg oral sildenafil 3 times per day for 12 weeks	Placebo n=91 participants at risk 20 mg of placebo 3 times per day for 12 weeks, followed by 20 mg open-label sildenafil 3 times per day for 12 weeks
Respiratory, thoracic and mediastinal disorders Dyspnea	14.6% 13/89 • Number of events 17	14.3% 13/91 • Number of events 15
Respiratory, thoracic and mediastinal disorders Cough	11.2% 10/89 • Number of events 10	7.7% 7/91 • Number of events 7
Respiratory, thoracic and mediastinal disorders Idiopathic pulmonary fibrosis	2.2% 2/89 • Number of events 2	5.5% 5/91 • Number of events 5
Infections and infestations Upper respiratory tract infection	7.9% 7/89 • Number of events 7	7.7% 7/91 • Number of events 8
Infections and infestations Bronchitis	1.1% 1/89 • Number of events 1	6.6% 6/91 • Number of events 6
Nervous system disorders Headache	20.2% 18/89 • Number of events 22	18.7% 17/91 • Number of events 19
Nervous system disorders Dizziness	9.0% 8/89 • Number of events 9	5.5% 5/91 • Number of events 5
Gastrointestinal disorders Diarrhoea	13.5% 12/89 • Number of events 12	8.8% 8/91 • Number of events 8
Gastrointestinal disorders Nausea	4.5% 4/89 • Number of events 4	5.5% 5/91 • Number of events 6
General disorders Oedema peripheral	10.1% 9/89 • Number of events 11	8.8% 8/91 • Number of events 9
Vascular disorders Hypotension	5.6% 5/89 • Number of events 5	2.2% 2/91 • Number of events 2

Additional Information

Kevin J Anstrom, PhD

Duke Clinical Research Institute

Phone: 919-668-8902

Email: kevin.anstrom@duke.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place