Trial Outcomes & Findings for Sildenafil in HFpEF (Heart Failure With Preserved Ejection Fraction) and PH (NCT NCT01726049)

NCT ID: NCT01726049

Last Updated: 2016-03-21

Results Overview

change of mean pulmonary artery pressure between baseline and 12 weeks measured by heart catheterisation

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 52 participants
• Primary outcome timeframe: baseline and 12 weeks
• Results posted on: 2016-03-21

Participant Flow

Stabile outpatients with heart failure with preserved ejection fraction (HFpEF) and signs of pulmonary hypertension (PH) on echocardiogram were referred for right heart cath as part of clinical care. After heart catheter measurements , eligible patients were asked for participation. Recruitment from october 2011 until september 2014

Participant milestones

Measure	Sildenafil Sildenafil: Sildenafil administered orally 3 times per day 20 mg for the first 2 weeks, followed by 3 times 60 mg for 10 weeks	Placebo Placebo: Placebo tablets 3 times per day 20 mg foor de first 2 weeks, followed by 3 times 60 mg for 10 weeks
Overall Study STARTED	26	26
Overall Study COMPLETED	21	22
Overall Study NOT COMPLETED	5	4

Reasons for withdrawal

Measure	Sildenafil Sildenafil: Sildenafil administered orally 3 times per day 20 mg for the first 2 weeks, followed by 3 times 60 mg for 10 weeks	Placebo Placebo: Placebo tablets 3 times per day 20 mg foor de first 2 weeks, followed by 3 times 60 mg for 10 weeks
Overall Study Death	1	1
Overall Study Adverse Event	4	1
Overall Study refused second HC	0	2

Baseline Characteristics

Sildenafil in HFpEF (Heart Failure With Preserved Ejection Fraction) and PH

Baseline characteristics by cohort

Measure	Sildenafil n=26 Participants Sildenafil: Sildenafil administered orally 3 times per day 20 mg for the first 2 weeks, followed by 3 times 60 mg for 10 weeks	Placebo n=26 Participants Placebo: Placebo tablets 3 times per day 20 mg foor de first 2 weeks, followed by 3 times 60 mg for 10 weeks	Total n=52 Participants Total of all reporting groups
Age, Continuous	72 years STANDARD_DEVIATION 12 • n=5 Participants	76 years STANDARD_DEVIATION 7 • n=7 Participants	74 years STANDARD_DEVIATION 10 • n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	17 Participants n=7 Participants	37 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment Netherlands	26 participants n=5 Participants	26 participants n=7 Participants	52 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline and 12 weeks

Population: 52 patients randomized. 26 Sildenafil arm: 26 placebo arm: change in mean pulmonary artery pressure could be evaluated in the intention to treat (ITT) analyses in 21 and 22 subjects of the Sildenafil and placebo treatment group

change of mean pulmonary artery pressure between baseline and 12 weeks measured by heart catheterisation

Outcome measures

Measure	Sildenafil n=21 Participants Sildenafil: Sildenafil administered orally 3 times per day 20 mg for the first 2 weeks, followed by 3 times 60 mg for 10 weeks	Placebo n=22 Participants Placebo: Placebo tablets 3 times per day 20 mg foor de first 2 weeks, followed by 3 times 60 mg for 10 weeks
Mean Pulmonary Artery Pressure Measured by Right Heart Catheterization	-2.4 mmHG Interval -4.5 to -0.3	-4.7 mmHG Interval -7.1 to -2.3

SECONDARY outcome

Timeframe: baseline and 12 weeks

Population: 52 patients randomized. 26 Sildenafil arm: 26 placebo arm: change in VO2max could be evaluated in the ITT analyses in 18 and 22 subjects of the Sildenafil and placebo treatment group

difference in change of VO2 max between baseline and 12 weeks between Sildenafil and placebo group

Outcome measures

Measure	Sildenafil n=18 Participants Sildenafil: Sildenafil administered orally 3 times per day 20 mg for the first 2 weeks, followed by 3 times 60 mg for 10 weeks	Placebo n=22 Participants Placebo: Placebo tablets 3 times per day 20 mg foor de first 2 weeks, followed by 3 times 60 mg for 10 weeks
VO2max	0.2 ml/kg/min Interval -0.9 to 1.4	0.7 ml/kg/min Interval -0.3 to 1.6

SECONDARY outcome

Timeframe: baseline and 12 weeks

Population: 52 patients randomized. 26 Sildenafil arm: 26 placebo arm: change in cardiac output could be evaluated in the ITT analyses in 20 and 22 subjects of the Sildenafil and placebo treatment group

difference in change of cardiac output between baseline and 12 weeks between Sildenafil and Placebo group

Outcome measures

Measure	Sildenafil n=20 Participants Sildenafil: Sildenafil administered orally 3 times per day 20 mg for the first 2 weeks, followed by 3 times 60 mg for 10 weeks	Placebo n=22 Participants Placebo: Placebo tablets 3 times per day 20 mg foor de first 2 weeks, followed by 3 times 60 mg for 10 weeks
Cardiac Output Measured Invasively by Right Heart Catheterization	-0.4 mililiter/min Interval -0.9 to 0.1	-0.2 mililiter/min Interval -0.5 to 0.1

SECONDARY outcome

Timeframe: baseline and 12 weeks

Population: 52 patients randomized. 26 Sildenafil arm: 26 placebo arm: change in wedge pressure could be evaluated in the ITT analyses in 21 and 22 subjects of the Sildenafil and placebo treatment group

Difference in change of wedge pressure between baseline and 12 weeks between Sildenafil group and Placebo group

Outcome measures

Measure	Sildenafil n=21 Participants Sildenafil: Sildenafil administered orally 3 times per day 20 mg for the first 2 weeks, followed by 3 times 60 mg for 10 weeks	Placebo n=22 Participants Placebo: Placebo tablets 3 times per day 20 mg foor de first 2 weeks, followed by 3 times 60 mg for 10 weeks
Wedge Pressure Measured Invasively by Right Heart Catheterization	-0.5 mmHg Interval -1.9 to 1.0	-3.5 mmHg Interval -5.2 to -1.8

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

Outcome measures

Outcome data not reported

Adverse Events

Sildenafil

Serious events: 4 serious events

Other events: 22 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Measure	Sildenafil n=26 participants at risk Sildenafil: Sildenafil administered orally 3 times per day 20 mg for the first 2 weeks, followed by 3 times 60 mg for 10 weeks	Placebo n=26 participants at risk Placebo: Placebo tablets 3 times per day 20 mg foor de first 2 weeks, followed by 3 times 60 mg for 10 weeks
Gastrointestinal disorders intestinal infarction	0.00% 0/26 • 3 months	3.8% 1/26 • 3 months
Cardiac disorders cardiac failure	3.8% 1/26 • 3 months	0.00% 0/26 • 3 months
Respiratory, thoracic and mediastinal disorders pneumonia	3.8% 1/26 • 3 months	7.7% 2/26 • 3 months
Vascular disorders pseudoaneurysma	3.8% 1/26 • 3 months	0.00% 0/26 • 3 months
Vascular disorders medical device complication	3.8% 1/26 • 3 months	0.00% 0/26 • 3 months

Other adverse events

Measure	Sildenafil n=26 participants at risk Sildenafil: Sildenafil administered orally 3 times per day 20 mg for the first 2 weeks, followed by 3 times 60 mg for 10 weeks	Placebo n=26 participants at risk Placebo: Placebo tablets 3 times per day 20 mg foor de first 2 weeks, followed by 3 times 60 mg for 10 weeks
General disorders headache	15.4% 4/26 • 3 months	11.5% 3/26 • 3 months
Gastrointestinal disorders nausea	7.7% 2/26 • 3 months	7.7% 2/26 • 3 months
Nervous system disorders dizziness	3.8% 1/26 • 3 months	11.5% 3/26 • 3 months
Eye disorders visual impairment	0.00% 0/26 • 3 months	19.2% 5/26 • 3 months
Musculoskeletal and connective tissue disorders myalgia	15.4% 4/26 • 3 months	15.4% 4/26 • 3 months
Infections and infestations respiratory tract infection	34.6% 9/26 • 3 months	11.5% 3/26 • 3 months
Respiratory, thoracic and mediastinal disorders chest pain	7.7% 2/26 • 3 months	3.8% 1/26 • 3 months

Additional Information

E.S. Hoendermis, MD, PHD

University Hospital Groningen, NL

Phone: 0031503616161

Email: e.s.hoendermis@umcg.nl

Results disclosure agreements

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