Erectile Dysfunction, Heart Failure, Heart Failure, Systolic
Conditions
Keywords
heart failure, systolic heart failure, heart failure with reduced ejection fraction, erectile dysfunction, Enalapril, Enalaprilat, LCZ696, Sacubitril/valsartan
Brief summary
The purpose of this study was to determine the effect of sacubitril/valsartan (LCZ696) vs. Enalapril on improvement in erectile function and ability in male patients with chronic heart failure with reduced ejection fraction and erectile dysfunction.
Detailed description
The purpose of this study was to evaluate the effect of sacubitril/valsartan in improving erectile function in male patients with chronic heart failure (NYHA II) and reduced ejection fraction (HFrEF) and erectile dysfunction (ED). Data from this study was intended to provide a thorough understanding of the impact of sacubitril/valsartan on male sexual function and therefore quality of life.
Interventions
DRUGLCZ696
sacubitril/valsartan 200 mg = 97 mg/103 mg bid sacubitril/valsartan film-coated tablets
Placebo to Enalapril 10 mg film-coated tablets
DRUGEnalapril
Enalapril 10 mg film-coated tablets
Placebo to LCZ696 200 mg = 97 mg/103 mg bid sacubitril/valsartan film-coated tablets
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Patients with a diagnosis of chronic heart failure (NYHA class II) and reduced ejection fraction (LVEF \< 40%) * Patients must be living in a stable and sexually active heterosexual partnership for at least 6 months prior study start * Patients must have a mild to moderate erectile dysfunction (determined by using the IIEF-5 questionnaire) * Patients must be on an ACEI or an ARB at a stable dose for at least 4 weeks prior study start * Patients must be literate in German Key
Exclusion criteria
* History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes, ACEIs, ARBs or NEP inhibitors, as well as known or suspected contraindications to the study drugs * Previous history of intolerance to recommended target doses of ACEIs or ARBs * Known history of angioedema * Current acute decompensated HF (exacerbation of chronic HF manifested by signs and symptoms that may require intravenous therapy) * Symptomatic hypotension * Impaired renal function * Penile anatomical defects and Peyronie's disease * Diabetes mellitus Type I or insulin-dependent Type II * Known prostate cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Erectile Function Score Using Index of Erectile Function (IIEF-15) | Week 12 (3 months) | The International Index of Erectile Function (IIEF-15) was used to assess erectile function in male patients with chronic heart failure. The IIEF-15 is a patient self-reported assessment of erectile dysfunction (ED) and consists of 15 questions assessing different aspects associated with ED. The domain evaluating erectile function consists of items 1, 2, 3, 4, 5 & 15 and its total score was used here. Total score range =1-30. Items 1-5 is 6-point Likert-type scale from '0' (= No sexual activity), '1' (=Almost never or never) to '5' (= Almost always or always). Items 15 is 5-point Likert-type scale from '1' (= very low) to '5 '(= very high). Higher score indicates better outcome |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Change From Baseline in Self-reported Frequency of Sexual Activity Per Week | Baseline, Week 4, Week 12 | Assessment of early-onset effect and end of study effect, regarding improvement in sexual activity, using patient's self-reported frequency of sexual activity per week. Patient was asked to complete a diary assessing sexual activity on a weekly basis |
| Summary of Change From Baseline in NT-proBNP Levels | Baseline, Week 4, Week 12 | Change in n-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels compared to baseline assessed at Week 4 and Week 12 |
Countries
Germany
Participant flow
Recruitment details
A total of 13 patients were randomized to the LCZ696 group and 14 patients were randomized to the enalapril group. Of these, 12 patients in the LCZ696 group and 13 patients in the enalapril group completed the study. One patient from the LCZ696 group discontinued due to Adverse Event and 1 patient from the enalapril group discontinued due to subject decision.
Pre-assignment details
A total of 13 patients were randomized to the LCZ696 group and 14 patients were randomized to the enalapril group. Of these, 12 patients in the LCZ696 group and 13 patients in the enalapril group completed the study. One patient from the LCZ696 group discontinued due to Adverse Event and 1 patient from the enalapril group discontinued due to subject decision.
Participants by arm
| Arm | Count |
|---|---|
| LCZ696 LCZ696 200 mg (sacubitril/valsartan 97 mg/103 mg) bid | 13 |
| Enalapril Enalapril 10 mg bid | 14 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Enalapril | Total | LCZ696 |
|---|---|---|---|
| Age, Continuous | 66.5 Years STANDARD_DEVIATION 7.8 | 65.0 Years STANDARD_DEVIATION 8.47 | 63.5 Years STANDARD_DEVIATION 9.18 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 27 Participants | 13 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 14 Participants | 27 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 14 |
| other Total, other adverse events | 7 / 13 | 5 / 14 |
| serious Total, serious adverse events | 1 / 13 | 1 / 14 |
Outcome results
Primary
Erectile Function Score Using Index of Erectile Function (IIEF-15)
The International Index of Erectile Function (IIEF-15) was used to assess erectile function in male patients with chronic heart failure. The IIEF-15 is a patient self-reported assessment of erectile dysfunction (ED) and consists of 15 questions assessing different aspects associated with ED. The domain evaluating erectile function consists of items 1, 2, 3, 4, 5 & 15 and its total score was used here. Total score range =1-30. Items 1-5 is 6-point Likert-type scale from '0' (= No sexual activity), '1' (=Almost never or never) to '5' (= Almost always or always). Items 15 is 5-point Likert-type scale from '1' (= very low) to '5 '(= very high). Higher score indicates better outcome
Time frame: Week 12 (3 months)
Population: All participants who received at least one dose of study treatment and had a valid assessment of the outcome measure
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LCZ696 | Erectile Function Score Using Index of Erectile Function (IIEF-15) | 15.1 Scores on a scale | Standard Error 2.15 |
| Enalapril | Erectile Function Score Using Index of Erectile Function (IIEF-15) | 12.2 Scores on a scale | Standard Error 2 |
p-value: 0.343295% CI: [-3.29, 9.01]Mixed Model Repeated Measures (MMRM)
Secondary
Summary of Change From Baseline in NT-proBNP Levels
Change in n-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels compared to baseline assessed at Week 4 and Week 12
Time frame: Baseline, Week 4, Week 12
Population: Full Analysis Set, including all participants who received at least one dose of study treatment
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| LCZ696 | Summary of Change From Baseline in NT-proBNP Levels | Week 4 | -369.00 pg/mL |
| LCZ696 | Summary of Change From Baseline in NT-proBNP Levels | Week 12 | -208.50 pg/mL |
| Enalapril | Summary of Change From Baseline in NT-proBNP Levels | Week 4 | -43.50 pg/mL |
| Enalapril | Summary of Change From Baseline in NT-proBNP Levels | Week 12 | -189.00 pg/mL |
Secondary
Summary of Change From Baseline in Self-reported Frequency of Sexual Activity Per Week
Assessment of early-onset effect and end of study effect, regarding improvement in sexual activity, using patient's self-reported frequency of sexual activity per week. Patient was asked to complete a diary assessing sexual activity on a weekly basis
Time frame: Baseline, Week 4, Week 12
Population: Full Analysis Set, including all participants who received at least one dose of study treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCZ696 | Summary of Change From Baseline in Self-reported Frequency of Sexual Activity Per Week | Week 4: | -1.6 Activities per week. | Standard Deviation 1.59 |
| LCZ696 | Summary of Change From Baseline in Self-reported Frequency of Sexual Activity Per Week | Week 12: | -1.4 Activities per week. | Standard Deviation 3.13 |
| Enalapril | Summary of Change From Baseline in Self-reported Frequency of Sexual Activity Per Week | Week 4: | -1.1 Activities per week. | Standard Deviation 1.97 |
| Enalapril | Summary of Change From Baseline in Self-reported Frequency of Sexual Activity Per Week | Week 12: | -2.0 Activities per week. | Standard Deviation 3.07 |