Trial Outcomes & Findings for Cardiovascular Effects of Chronic Sildenafil in Men With Type 2 Diabetes (NCT NCT00692237)

Results Overview

Diabetic cardiomyopathy and hypertrophy are characterized by an increase in cardiac torsion Normal value of rotation are \< 12°; in hypertrophic heart such values can raise up to 20-25°. A reduction in left ventricular wall rotation is a sign of improvement after removal of known causes of hypertrophy (for example after surgical repair of aortic stenosis). Based on previous studies a reduction of 3 degrees (°) is considered clinically significant.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

59 participants

Primary outcome timeframe

0 and + 3 months

Results posted on

2013-05-08

Participant Flow

Eligible men were recruited from the outpatient clinics of Policlinico Umberto I - Sapienza University Hospital of Rome between 2008 and 2009.

Overall 66 patients were eligible and enrolled; Seven were then excluded due to evidence of aneurysm of ascending aorta (1) on stress-Echo and of ischemic heart disease (6) at the first CMR. Fifty-nine patients were randomized.

Participant milestones

Participant milestones
Measure	Sildenafil Sildenafil citrate 100 mg/day (50+25+25)	Placebo Placebo 100 mg/day (50 + 25 + 25)
Overall Study STARTED	30	29
Overall Study COMPLETED	29	25
Overall Study NOT COMPLETED	1	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Sildenafil Sildenafil citrate 100 mg/day (50+25+25)	Placebo Placebo 100 mg/day (50 + 25 + 25)
Overall Study Withdrawal by Subject	1	3
Overall Study Adverse Event	0	1

Baseline Characteristics

Cardiovascular Effects of Chronic Sildenafil in Men With Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sildenafil n=30 Participants Sildenafil citrate 100 mg/day (50+25+25)	Placebo n=29 Participants Placebo 100 mg/day (50 + 25 + 25)	Total n=59 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	20 Participants n=5 Participants	20 Participants n=7 Participants	40 Participants n=5 Participants
Age, Categorical >=65 years	10 Participants n=5 Participants	9 Participants n=7 Participants	19 Participants n=5 Participants
Age Continuous	61 years STANDARD_DEVIATION 7 • n=5 Participants	59 years STANDARD_DEVIATION 7 • n=7 Participants	60 years STANDARD_DEVIATION 7 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants	29 Participants n=7 Participants	59 Participants n=5 Participants
Region of Enrollment Italy	30 participants n=5 Participants	29 participants n=7 Participants	59 participants n=5 Participants

PRIMARY outcome

Timeframe: 0 and + 3 months

Population: An overall sample size of 32 subjects (16 for each group) would thus have given a 90% power to detect the specified minimum detectable difference (3°) at a 2-sided significance level of 0.01; 59 patients were enrolled: 29 randomized to Sildenafil and 25 randomized to Placebo completed the trial. Analysis was per primary efficacy outcome (LV-q).

Diabetic cardiomyopathy and hypertrophy are characterized by an increase in cardiac torsion Normal value of rotation are \< 12°; in hypertrophic heart such values can raise up to 20-25°. A reduction in left ventricular wall rotation is a sign of improvement after removal of known causes of hypertrophy (for example after surgical repair of aortic stenosis). Based on previous studies a reduction of 3 degrees (°) is considered clinically significant.

Outcome measures

Outcome measures
Measure	Sildenafil n=29 Participants Patients randomized to receive sildenafil were instructed to take 3 capsules per day (25 mg at 8.00 a.m. + 25 mg at 4.00 p.m. + 50 mg at 10.00 p.m.) that were identical-looking to placebo capsules, for a duration of 3 months (12 weeks). The allocation list was produced using dedicated software by permuted-block randomization with 1:1 allocation using randomly sized blocks (4 to 8). The study was double-blinded.	Placebo n=25 Participants Patients randomized to receive placebo were instructed to take 3 capsules per day (1 at 8.00 a.m. + 1 at 4.00 p.m. + 1 at 10.00 p.m.) that were identical-looking to sildenafil capsules, for a duration of 3 months (12 weeks). The allocation list was produced using dedicated software by permuted-block randomization with 1:1 allocation using randomly sized blocks (4 to 8). The study was double-blinded.
Left Ventricular Torsion Defined as Change in Ventricular Mid-wall Rotation (°) Measured by Cine-Cardiac Magnetic Resonance (CMR) Imaging With Tagging, Before and After Three Months of Treatment With Sildenafil and Placebo (100 mg/Day).	-3.89 Degree angle (delta) Standard Deviation 3.11	2.13 Degree angle (delta) Standard Deviation 2.35

SECONDARY outcome

Timeframe: 0 and + 3 months

Population: We included in this analysis all the patients that concluded the study (Sildenafil group = 29; Placebo group = 25). The 4 randomized patients who discontinued, did not perform the second after-treatment CMR evaluation. Analysis was "per protocol".

The volume of blood within a ventricle immediately before a contraction is known as the end-diastolic volume; the volume of blood left in a ventricle at the end of contraction is end-systolic volume. The difference between end-diastolic volume and end-systolic volumes is the volume of blood ejected with each beat. Ejection fraction (Ef) is the fraction of the end-diastolic volume that is ejected with each beat; expressed as percentage of EDV. This is a measure of cardiac performance that can be deteriorated in diabetic cardiomyopathy.

Outcome measures

Outcome measures
Measure	Sildenafil n=29 Participants Patients randomized to receive sildenafil were instructed to take 3 capsules per day (25 mg at 8.00 a.m. + 25 mg at 4.00 p.m. + 50 mg at 10.00 p.m.) that were identical-looking to placebo capsules, for a duration of 3 months (12 weeks). The allocation list was produced using dedicated software by permuted-block randomization with 1:1 allocation using randomly sized blocks (4 to 8). The study was double-blinded.	Placebo n=25 Participants Patients randomized to receive placebo were instructed to take 3 capsules per day (1 at 8.00 a.m. + 1 at 4.00 p.m. + 1 at 10.00 p.m.) that were identical-looking to sildenafil capsules, for a duration of 3 months (12 weeks). The allocation list was produced using dedicated software by permuted-block randomization with 1:1 allocation using randomly sized blocks (4 to 8). The study was double-blinded.
Ejection Fraction (EF) Defined as the Volume of Blood Ejected With Each Beat Was Measured on Cine-Cardiac Magnetic Resonance (CMR) Images Before and After Three Months Treatment With Sildenafil and Placebo (100 mg/Day).	2.77 Percentage % of volume (delta) Standard Deviation 4.36	3.14 Percentage % of volume (delta) Standard Deviation 5.87

Adverse Events

Sildenafil

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sildenafil n=30 participants at risk Sildenafil citrate 100 mg/day (50+25+25)	Placebo n=29 participants at risk Placebo 100 mg/day (50 + 25 + 25)
Blood and lymphatic system disorders Portal Vein Thrombosis	0.00% 0/30	3.4% 1/29 • Number of events 1

Other adverse events

Adverse event data not reported

Additional Information

Dr Andrea Isidori

Sapienza University of Rome

Phone: +39 0649970540

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place