Trial Outcomes & Findings for Sildenafil Exercise: Role of PDE5 Inhibition (NCT NCT04039087)

Last Updated: 2026-08-28

Results Overview

Exercise capacity, an objective measurement of exercise tolerance, predicts mortality in patients with CF. The mechanisms for exercise intolerance in CF have yet to be fully elucidated and further understanding could improve clinical outcomes and survival in CF. Preliminary data from two independent proof-of-concept clinical trials support the use of sildenafil to improve exercise capacity, cardiac function, and quality of life in CF

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

31 participants

Primary outcome timeframe

Change in distance walked between week 1 and week 13

Results posted on

2026-08-28

Participant Flow

Participants were recruited from National Jewish Health in Denver, Colorado, and from Augusta University in Augusta, Georgia. Children and adults were enrolled at Augusta University and only adults were recruited at National Jewish Health. Participants were identified using the Cystic Fibrosis Foundation Patient Registry (CFFPR) and when attending CF clinic at the respective clinics. Potential participants were approached in person at clinic or by telephone between September 2019 and June 2024.

Participant milestones

Participant milestones
Measure	Sildenafil Active sildenafil 40 mg p.o. three times per day	Placebo Arm Placebo p.o. three times per day
Overall Study STARTED	15	16
Overall Study COMPLETED	11	15
Overall Study NOT COMPLETED	4	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Sildenafil Exercise: Role of PDE5 Inhibition

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sildenafil n=15 Participants active sildenafil 40 mg p.o. three times per day	Placebo Arm n=16 Participants placebo three times per day	Total n=31 Participants Total of all reporting groups
Age, Continuous	32.2 Years STANDARD_DEVIATION 11.7 • n=31 Participants	32.0 Years STANDARD_DEVIATION 9.2 • n=49 Participants	32.1 Years STANDARD_DEVIATION 10.3 • n=80 Participants
Sex: Female, Male Female	8 Participants n=31 Participants	6 Participants n=49 Participants	14 Participants n=80 Participants
Sex: Female, Male Male	7 Participants n=31 Participants	10 Participants n=49 Participants	17 Participants n=80 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=31 Participants	1 Participants n=49 Participants	1 Participants n=80 Participants
Race (NIH/OMB) Asian	0 Participants n=31 Participants	0 Participants n=49 Participants	0 Participants n=80 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=31 Participants	0 Participants n=49 Participants	0 Participants n=80 Participants
Race (NIH/OMB) Black or African American	1 Participants n=31 Participants	2 Participants n=49 Participants	3 Participants n=80 Participants
Race (NIH/OMB) White	13 Participants n=31 Participants	12 Participants n=49 Participants	25 Participants n=80 Participants
Race (NIH/OMB) More than one race	1 Participants n=31 Participants	0 Participants n=49 Participants	1 Participants n=80 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=31 Participants	1 Participants n=49 Participants	1 Participants n=80 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=31 Participants	1 Participants n=49 Participants	3 Participants n=80 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=31 Participants	15 Participants n=49 Participants	28 Participants n=80 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=31 Participants	0 Participants n=49 Participants	0 Participants n=80 Participants

PRIMARY outcome

Timeframe: Change in distance walked between week 1 and week 13

Outcome measures

Outcome measures
Measure	Sildenafil n=15 Participants Active sildenafil 40 mg p.o. three times per day	Placebo Arm n=16 Participants placebo three times per day
6 Minute Walk Distance (6MWD)	-4 Meters (m) Interval -32.0 to 25.0	27 Meters (m) Interval 2.0 to 52.0

SECONDARY outcome

Timeframe: Quality of life assessed at weeks 1 and 13

The respiratory domain of the validated CF-specific quality of life measure. The CFQ-R Respiratory domain score (scale 0-100 with higher scores indicating better quality of life).

Outcome measures

Outcome measures
Measure	Sildenafil n=15 Participants Active sildenafil 40 mg p.o. three times per day	Placebo Arm n=16 Participants placebo three times per day
Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score	0.5 Units on a scale Interval -8.4 to 9.4	6.3 Units on a scale Interval -1.3 to 13.9

Adverse Events

Sildenafil

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo Arm

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sildenafil n=15 participants at risk Active sildenafil 40 mg p.o. three times per day	Placebo Arm n=16 participants at risk Placebo p.o. three times per day
Respiratory, thoracic and mediastinal disorders Pulmonary Exacerbation	6.7% 1/15 • From randomization until end of follow-up, up to 13 weeks	0.00% 0/16 • From randomization until end of follow-up, up to 13 weeks

Other adverse events

Additional Information

Jennifer Taylor, MD, MSCS, ATSF; Professor, Dept of Medicine and Pediatrics, Medical Director, CRS

National Jewish Health

Phone: 303-270-2764

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Sildenafil n=15 participants at risk Active sildenafil 40 mg p.o. three times per day	Placebo Arm n=16 participants at risk Placebo p.o. three times per day
Nervous system disorders Headache	0.00% 0/15 • From randomization until end of follow-up, up to 13 weeks	12.5% 2/16 • From randomization until end of follow-up, up to 13 weeks
Nervous system disorders Flushing	0.00% 0/15 • From randomization until end of follow-up, up to 13 weeks	12.5% 2/16 • From randomization until end of follow-up, up to 13 weeks
Nervous system disorders Body Aches	6.7% 1/15 • From randomization until end of follow-up, up to 13 weeks	6.2% 1/16 • From randomization until end of follow-up, up to 13 weeks
Respiratory, thoracic and mediastinal disorders Rhinitis	6.7% 1/15 • From randomization until end of follow-up, up to 13 weeks	18.8% 3/16 • From randomization until end of follow-up, up to 13 weeks
Nervous system disorders Fatigue	0.00% 0/15 • From randomization until end of follow-up, up to 13 weeks	6.2% 1/16 • From randomization until end of follow-up, up to 13 weeks
Respiratory, thoracic and mediastinal disorders Sinusitis	13.3% 2/15 • From randomization until end of follow-up, up to 13 weeks	0.00% 0/16 • From randomization until end of follow-up, up to 13 weeks
Respiratory, thoracic and mediastinal disorders Wheezing	13.3% 2/15 • From randomization until end of follow-up, up to 13 weeks	0.00% 0/16 • From randomization until end of follow-up, up to 13 weeks
Respiratory, thoracic and mediastinal disorders Chest tightness	6.7% 1/15 • From randomization until end of follow-up, up to 13 weeks	6.2% 1/16 • From randomization until end of follow-up, up to 13 weeks
Respiratory, thoracic and mediastinal disorders Chest congestion	0.00% 0/15 • From randomization until end of follow-up, up to 13 weeks	12.5% 2/16 • From randomization until end of follow-up, up to 13 weeks
Respiratory, thoracic and mediastinal disorders Shortness of breath	6.7% 1/15 • From randomization until end of follow-up, up to 13 weeks	6.2% 1/16 • From randomization until end of follow-up, up to 13 weeks
Cardiac disorders Tachycardia	0.00% 0/15 • From randomization until end of follow-up, up to 13 weeks	6.2% 1/16 • From randomization until end of follow-up, up to 13 weeks
Cardiac disorders Abnormal EKG	0.00% 0/15 • From randomization until end of follow-up, up to 13 weeks	6.2% 1/16 • From randomization until end of follow-up, up to 13 weeks
Cardiac disorders Edema	0.00% 0/15 • From randomization until end of follow-up, up to 13 weeks	6.2% 1/16 • From randomization until end of follow-up, up to 13 weeks
Respiratory, thoracic and mediastinal disorders Hoarse Voice	13.3% 2/15 • From randomization until end of follow-up, up to 13 weeks	0.00% 0/16 • From randomization until end of follow-up, up to 13 weeks
Respiratory, thoracic and mediastinal disorders Cough / Increased cough	6.7% 1/15 • From randomization until end of follow-up, up to 13 weeks	6.2% 1/16 • From randomization until end of follow-up, up to 13 weeks
Respiratory, thoracic and mediastinal disorders Sore Throat	6.7% 1/15 • From randomization until end of follow-up, up to 13 weeks	0.00% 0/16 • From randomization until end of follow-up, up to 13 weeks
Infections and infestations Fever	0.00% 0/15 • From randomization until end of follow-up, up to 13 weeks	6.2% 1/16 • From randomization until end of follow-up, up to 13 weeks
Infections and infestations COVID-19 Positive	0.00% 0/15 • From randomization until end of follow-up, up to 13 weeks	6.2% 1/16 • From randomization until end of follow-up, up to 13 weeks
Infections and infestations Streptococcal Pharyngitis	0.00% 0/15 • From randomization until end of follow-up, up to 13 weeks	6.2% 1/16 • From randomization until end of follow-up, up to 13 weeks
Respiratory, thoracic and mediastinal disorders Mucus impaction	0.00% 0/15 • From randomization until end of follow-up, up to 13 weeks	6.2% 1/16 • From randomization until end of follow-up, up to 13 weeks
Endocrine disorders Hair loss	6.7% 1/15 • From randomization until end of follow-up, up to 13 weeks	0.00% 0/16 • From randomization until end of follow-up, up to 13 weeks
Nervous system disorders Dysgeusia	6.7% 1/15 • From randomization until end of follow-up, up to 13 weeks	0.00% 0/16 • From randomization until end of follow-up, up to 13 weeks
Renal and urinary disorders Pyelonephritis	6.7% 1/15 • From randomization until end of follow-up, up to 13 weeks	0.00% 0/16 • From randomization until end of follow-up, up to 13 weeks