COmparing arNi and Ace For Improving Erectile Dysfunction in mEN With reduCed Ejection Fraction Heart Failure: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for COmparing arNi and Ace For Improving Erectile Dysfunction in mEN With reduCed Ejection Fraction Heart Failure (NCT03917459), a randomized phase 3 study. The primary outcome is Erectile Function Score Using Index of Erectile Function (IIEF-15).

2. Clinical Question

3. Trial Design

This was a randomized, triple-masked, parallel-group, phase 3 study. The registry lists Novartis Pharmaceuticals as the sponsor and describes the study as comparing sacubitril/valsartan, also called LCZ696, with enalapril for erectile function in patients with heart failure with reduced ejection fraction and erectile dysfunction. The study status is completed. The recorded start date is 2019-04-16, and the primary completion date is 2021-05-25.

The registry reports an enrollment of 27. The primary outcome summaries are based on 12 participants in the LCZ696 arm and 13 in the enalapril arm. The primary outcome population is described as participants who received at least one dose of study treatment and had a valid outcome assessment. These numbers describe the posted outcome summaries and should not be treated as proof of why the number differs from the enrollment figure; reasons for the difference are not reported in the registry record.

The active treatments are described as LCZ696 200 mg (sacubitril/valsartan 97 mg/103 mg bid) and enalapril 10 mg. The intervention listings also include an enalapril matching placebo and an LCZ696 matching placebo. Randomization and triple masking are reported, but allocation procedures, the specific people masked, and details of how the masking was maintained are not reported in the registry record. The randomization ratio and any stratification factors are also not reported in the registry record.

The primary endpoint was measured at Week 12 (3 months). Two secondary outcomes are listed: change from baseline in self-reported frequency of sexual activity per week and change from baseline in NT-proBNP levels. The registry record does not report enough detail to establish how those secondary outcomes were analyzed or how their results relate to the primary comparison. The original design assumptions, including any planned sample-size justification, are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who received at least one dose of study treatment and had a valid assessment of the outcome measure

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: A total of 27 patients were included in the Full Analysis Set (FAS) and safety set.

6. Primary Endpoint

The registry lists the primary outcome as Erectile Function Score Using Index of Erectile Function (IIEF-15), measured over Week 12 (3 months).

The primary endpoint was the erectile-function score from the International Index of Erectile Function (IIEF-15) at Week 12 (3 months). The IIEF-15 is a patient self-reported assessment of erectile dysfunction and contains 15 questions covering different aspects associated with erectile dysfunction. The endpoint uses the erectile-function domain, formed from items 1, 2, 3, 4, 5 and 15, with its total score used as the outcome.

The domain score ranges from 1-30. Items 1-5 use a 6-point Likert-type scale, from 0 for no sexual activity and 1 for almost never or never to 5 for almost always or always. Item 15 uses a 5-point Likert-type scale, from 1 for very low to 5 for very high. Higher scores indicate a better outcome. These response options matter when interpreting the score: the outcome reflects participants’ answers about multiple aspects of sexual function rather than a single clinical event or laboratory measure.

A self-reported score is relevant to a question about erectile function because it records participants’ own assessments of the experiences the study set out to evaluate. It also means that the endpoint is a scale score, not a direct count of events. The registry record identifies the score and assessment time, but does not report a threshold for a clinically important change or a minimum difference that would be considered meaningful to participants. The posted arm values are least-squares means with standard errors, rather than raw individual observations.

7. Results Posted in the Registry

• Enalapril: mean 12.20 versus 15.10 on control; difference -2.90 (95% CI -8.66 to 2.86), standardized effect d = -0.40; z-test p = 0.323.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it is a numerical score on the IIEF-15 erectile-function domain. A continuous outcome can take a range of score values, so the analysis can compare group averages rather than only the number of participants who meet a yes-or-no definition. In this study, the posted group summaries are least-squares means, and their reported dispersion is the standard error. A least-squares mean is a model-based estimate of a group mean; it is not necessarily the same as the simple arithmetic average of the observed scores. The registry record does not report the model’s full specification or the covariates, if any, used to obtain these estimates.

What does the treatment difference represent?

A treatment difference describes the estimated separation between the groups on the outcome scale. The sponsor’s posted estimate is 2.9 points for the contrast reported as LCZ696 relative to enalapril. Because higher IIEF-15 scores indicate better outcome, a positive contrast in that order points toward a higher score in the LCZ696 group. In the unadjusted recalculation, the contrast is written in the reverse order, enalapril relative to LCZ696, and is -2.9. Reversing the order reverses the sign, while the underlying comparison is between the same two posted group means.

The estimate is a point estimate: one value representing the fitted or recalculated difference. It should be read together with its uncertainty. Different analytic methods can produce different uncertainty estimates, even when their central estimates are closely related. The sponsor used a Mixed Model Repeated Measures analysis. The recalculation uses posted summary information and is unadjusted. The registry record does not report enough detail to reproduce the sponsor’s model or determine precisely which assumptions distinguish it from the simple recalculation.

What does a confidence interval tell the reader?

A confidence interval gives a range of estimates compatible with the data and the analysis under its assumptions. It communicates uncertainty around the point estimate; it is not a list of outcomes observed in individual participants. The sponsor’s 95% interval ranges from -3.29 to 9.01 for its treatment contrast. Since zero lies within this interval, the posted result is compatible with no between-group difference as well as with differences favoring either group. The interval’s width is also a warning that the estimate is not highly precise.

The recalculated interval ranges from -8.655 to 2.855 for the reverse contrast. It also contains zero. Its bounds should not be compared with the sponsor’s as if they were generated by the same model: the recalculation is unadjusted and uses an approximation from summary statistics, whereas the sponsor reports a repeated-measures model analysis. The registry record does not provide the repeated-measures data needed to independently reconstruct that model.

How should the p-values be read?

The sponsor reports p = 0.343 for its model-based analysis. The unadjusted recalculation reports p = 0.323. A p-value assesses how unusual data at least as incompatible with a null hypothesis of no difference would be under that hypothesis and the assumptions of the test. It is not the probability that the null hypothesis is true, nor does it measure the size or importance of the treatment difference. Neither p-value, taken alone, answers whether a difference is meaningful to participants. The two values differ because they come from different analyses, and the sponsor’s model-based result is the registry’s reported analysis.

A result that does not meet a conventional significance threshold is not evidence that the treatments are identical. Establishing equivalence would require an equivalence framework and a prespecified margin; establishing noninferiority would likewise require a specified design and margin. Those details are not reported in the registry record. The appropriate reading is that the posted data do not provide a statistically clear difference in the sponsor’s analysis, while the uncertainty leaves a broad range of effects plausible.

Why can repeated measurements matter?

A Mixed Model Repeated Measures analysis is a general statistical approach for outcomes measured more than once. In general, it can model the pattern of repeated observations over time and account for the fact that measurements from the same participant are related rather than independent. Depending on its specification, such a model can use information from multiple assessment times to estimate a treatment contrast at a selected time. The endpoint is at Week 12 (3 months), but the registry record does not report the model’s time points, covariance structure, fixed effects, or handling of missing repeated measurements. Those details should not be inferred from the method name alone.

Repeated-measures models are not automatically free from assumptions. In general, the validity of their estimates depends on how the outcome trajectory and within-participant correlation are modeled, as well as assumptions about missing data. The registry record does not report the diagnostics, sensitivity analyses, or missing-data assumptions used in the sponsor’s analysis. Therefore, the method can be identified, but the adequacy of its implementation cannot be fully assessed from the reported information.

Why does the small outcome group size matter?

The endpoint summaries include 12 participants in the LCZ696 group and 13 in the enalapril group. General statistical principles indicate that limited group sizes can make treatment estimates less stable and leave less information for assessing the spread of outcomes. A few unusually high or low observations may have appreciable influence on a mean. The confidence interval communicates some of this uncertainty, but it does not reveal the individual score distribution. The registry record does not report individual-level endpoint values, the distribution of scores, or an analysis of sensitivity to influential observations.

For a continuous score, the standard error describes uncertainty in an estimated mean, not the spread of individual participants’ scores. The reported standard errors are 2.15 for LCZ696 and 2.0 for enalapril. They should not be read as standard deviations. The recalculation estimates a pooled standard deviation of 7.325 using an approximation from the reported standard errors and group sizes; that is a recalculated quantity, not a directly posted dispersion measure. In general, greater variability among individual scores makes it harder to estimate a group difference precisely.

Finally, statistical interpretation depends on both the design and the analysis population. Randomization supports a comparison between assigned groups, but the primary outcome population is defined by having received at least one dose and having a valid outcome assessment. The registry record does not report whether an intention-to-treat analysis was performed, how many randomized participants lacked a valid endpoint, or what procedures were used for missing values. The analysis population and missing-data approach therefore limit how far causal conclusions can be extended beyond the reported comparison.

10. Confidence Intervals and Precision

The sponsor’s 95% confidence interval for the treatment difference extends from -3.29 to 9.01 points. The point estimate is 2.9 points, but the interval includes zero. It also includes estimates in the direction of a lower score with LCZ696 and estimates in the direction of a higher score with LCZ696. This broad span means the data do not pin down the size or direction of the difference with much precision.

The interval is more informative than the point estimate alone. A single estimate can suggest a direction, but it does not indicate how uncertain that estimate is. Here, the uncertainty encompasses no difference and a range of nonzero differences. The registry does not report a threshold for a clinically important difference on the IIEF-15 erectile-function score, so the clinical importance of particular values within the interval cannot be determined from the record.

The unadjusted recalculation gives a 95% confidence interval from -8.655 to 2.855 for enalapril minus LCZ696. Its order is reversed relative to the sponsor contrast, but it likewise includes zero. Its precision should not be directly substituted for that of the sponsor analysis because it is based on an unadjusted calculation from summary statistics rather than the Mixed Model Repeated Measures analysis.

The endpoint summaries include 12 and 13 participants. In general, smaller samples tend to provide less information about the population difference, especially when individual scores vary. The reported standard errors describe uncertainty in the group means; they do not show the full distribution of participant scores. The registry record does not report individual observations or a clinically important score threshold, so the uncertainty can be described statistically but not translated into a firm conclusion about practical importance.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are illustrations based on the observed effect, not a reconstruction of the trial’s original design. They use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set as a stated fraction of the observed effect. The original trial’s sample-size justification and design assumptions are not reported in the registry record.

For this continuous outcome, the figures are participants per arm, not total events. The 80% power column indicates the number of participants per arm in a hypothetical future study that would give an 80% probability of detecting the specified effect under the stated assumptions, if that effect and the model assumptions held. The 90% power column expresses the corresponding planning target at 90% probability. These are design probabilities under assumptions, not guarantees about what a future study will find.

The planning rows vary the effect from 100% of the observed effect to 75% and 50% of the observed effect. The smaller the effect targeted for detection, the more participants are needed per arm under the same assumptions. The listed values are 101 and 135 participants per arm for 100% of the observed effect; 179 and 239 for 75%; and 401 and 537 for 50%, for the 80% and 90% power targets respectively.

These figures should be read as planning illustrations rather than evidence about the probability that the completed study detected an effect. They are not observed power. Their relevance depends on the observed effect being a reasonable planning estimate, and the observed effect in a small study may be imprecise. The registry record does not report the original sample-size calculation, so the illustrations should not be interpreted as the planned enrollment target for this trial.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -2.900; pooled standard deviation σ = 7.325.
2. n = 2 × (1.96 + 0.842)² × 7.325² / -2.900² = 100.2, rounded up to 101 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -2.9                      # observed difference in means
sigma <- 7.32526895188097                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(3917459)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 101 (80% power), 135 (90% power)
 75% of observed effect: n per arm = 179 (80% power), 239 (90% power)
 50% of observed effect: n per arm = 401 (80% power), 537 (90% power)
power.t.test: 101.1 
Simulated power at n = 101 per arm: 0.800 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Analyses Reported by the Sponsor

The sponsor’s own posted analysis is a Mixed Model Repeated Measures analysis. It reports an estimated treatment difference of 2.9, a 95% confidence interval from -3.29 to 9.01, and p = 0.343. This is the registry’s model-based result and should be used as the main inferential finding.

The unadjusted recalculation is derived from the posted group summaries. It expresses the contrast as enalapril minus LCZ696, giving -2.9, with a confidence interval from -8.655 to 2.855 and an unadjusted p-value of 0.323. Its sign is opposite to the sponsor estimate because the group order is reversed. Both approaches point to a contrast of similar direction when their sign conventions are aligned, and both intervals include zero.

The calculations are not interchangeable. The sponsor’s model uses a repeated-measures approach, while the recalculation is an unadjusted comparison based on summary statistics and an approximation. The registry record does not report enough model detail or individual-level data to reproduce the sponsor analysis independently. Consequently, the recalculation is best treated as a transparent secondary check on the posted summaries, not as a replacement for the sponsor’s analysis.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists two secondary outcomes in addition to the primary erectile-function score: change from baseline in self-reported frequency of sexual activity per week and change from baseline in NT-proBNP levels. The record reports three outcome measures and one analysis. The primary result should be distinguished from these secondary outcomes; their presence does not establish that they were used to confirm the primary finding.

When a study examines multiple outcomes or makes multiple comparisons, the chance of at least one apparently unusual result can increase. General statistical practice may address this through a prespecified hierarchy, adjustment procedures, or a clearly designated primary outcome. The registry identifies a primary endpoint, but multiplicity procedures, any testing hierarchy, and whether analyses were adjusted for multiple comparisons are not reported in the registry record. The reported p-value should therefore be read as the result of the posted analysis, without assuming an adjustment that is not documented.

The primary endpoint population includes participants who received at least one dose of study treatment and had a valid assessment. The registry record does not report the number randomized in each arm, the number lacking a valid endpoint, reasons for missing outcome data, or the method used to handle missing observations. Although the reported method is Mixed Model Repeated Measures, the record does not state the assumptions made about missingness or whether sensitivity analyses tested those assumptions.

The record also does not report whether the primary analysis followed an intention-to-treat principle, how participants were handled after treatment discontinuation, or whether any per-protocol or other analysis populations were used. These details matter because excluding participants without valid assessments can affect the composition of the analyzed groups. Randomization describes assignment, but it does not by itself establish that all randomized participants contributed to the reported endpoint analysis.

The original statistical analysis plan, protocol-level outcome definitions beyond the posted description, and any prespecified interim analyses are not reported in the registry record. As a result, the available information supports interpretation of the posted endpoint estimate and its uncertainty, but not a full audit of prespecification, missing-data handling, or multiplicity control.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypertensive crisis (7.7%), cardiac arrest (7.1%).

The registry reports serious adverse event figures for 13 participants at risk in the LCZ696 group and 14 in the enalapril group. One participant in each group is listed as affected by a serious adverse event. Deaths are reported as 0 in each group. These are descriptive counts from the posted safety record; they do not by themselves establish whether a treatment caused an event or whether one treatment is safer than the other.

The listed serious-event terms are hypertensive crisis at 7.7% and cardiac arrest at 7.1%. The record presents these as top serious-event terms. With small groups, event counts and percentages can change substantially with a small number of participants, and the terms should be read in the context of the number at risk. The registry record does not report enough detail to determine event timing, relatedness to treatment, severity beyond the serious-event classification, or the basis for the listed percentages.

Other adverse events are reported for 7 of 13 participants in the LCZ696 group and 5 of 14 in the enalapril group. These figures are separate from the serious adverse event counts and should not be conflated with them. They are descriptive totals and do not provide a comparative statistical analysis. The study’s small outcome and safety groups limit how much can be inferred about uncommon harms. These data are a record of reported events, not a complete basis for an individual treatment decision.

16. What the Result Does, and Does Not, Mean

The primary result is an estimated difference in the Week 12 (3 months) IIEF-15 erectile-function score between randomized groups. The sponsor’s model-based estimate is 2.9 points, with a 95% confidence interval from -3.29 to 9.01 and p = 0.343. The estimate is positive for the LCZ696-versus-enalapril contrast, while the interval includes zero. The posted data therefore do not establish a statistically clear between-group difference in this outcome at the reported time point.

This is not the same as showing that the treatments have identical effects. The confidence interval remains compatible with effects in either direction, and the record does not report an equivalence or noninferiority design. Without a prespecified clinical-importance threshold for the score, the estimate also cannot be classified from the registry record as definitely meaningful or definitely unimportant to participants. The result is best understood as uncertain rather than as proof of no effect.

The study addressed a specific population: men with chronic heart failure with reduced ejection fraction and erectile dysfunction. The primary analysis included participants who received at least one dose and had a valid endpoint assessment. Its findings should not automatically be extended to people with other conditions, to participants outside that analysis population, or to outcomes not reported in the primary analysis.

The endpoint is a self-reported score assessing several aspects of erectile function. It captures participants’ reported experiences and is not a direct measure of every dimension of sexual health or overall heart-failure status. The listed secondary outcomes concern sexual-activity frequency and NT-proBNP, but their results are not presented in the information summarized for the primary comparison. No conclusion about those outcomes follows from the primary score alone.

The result also does not establish longer-term effects, since the primary assessment was at Week 12 (3 months). The registry record does not report a clinically important difference threshold, detailed missing-data procedures, or all elements of the analysis plan. These gaps, along with the limited endpoint group sizes and the breadth of the confidence interval, constrain the strength and reach of conclusions drawn from the posted result.

17. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the distinction between a point estimate and the uncertainty surrounding it. The sponsor’s estimate is 2.9 points in the LCZ696-versus-enalapril direction, but its confidence interval ranges from -3.29 to 9.01. The point estimate alone might suggest a direction; the interval shows why that direction should not be treated as a settled finding. It includes no difference and values on both sides of zero.

It also shows why a nonsignificant result is not proof of equivalence. The sponsor reports p = 0.343, but a p-value does not establish that effects are the same. The interval remains wide enough to include a range of differences. A formal equivalence or noninferiority question requires a design and prespecified margin, neither of which is reported in the registry record.

The comparison of the sponsor’s Mixed Model Repeated Measures result with an unadjusted recalculation highlights the importance of identifying the analysis behind a number. The recalculation reverses the contrast order, so its sign is negative rather than positive, and it uses a different method. Reading both the contrast direction and the analysis method prevents a sign change or modest p-value difference from being mistaken for a reversal of the underlying finding.

Finally, the small outcome groups make precision especially important. The posted summaries include 12 and 13 participants, and the confidence interval conveys substantial uncertainty. The planning illustrations further show, under their assumptions, that targeting smaller effects requires more participants per arm. They are not the original design rationale, but they demonstrate a general feature of statistical planning: a study must be sized in relation to the effect it aims to detect and the uncertainty of the measure.

18. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry reports an enrollment of 27, while the primary outcome summaries include 12 participants in the LCZ696 group and 13 in the enalapril group. The primary analysis population is defined by receiving at least one dose and having a valid assessment. The reasons for the difference between enrollment and the endpoint group sizes, including whether it reflects missing data, exclusions, or another process, are not reported in the registry record.

The outcome groups are small, and the sponsor’s confidence interval is broad, spanning estimates below and above no difference. This limits precision and makes it difficult to determine the size of any between-group difference. The registry record does not provide individual scores, score distributions, or sensitivity analyses that would show how robust the mean comparison is to the observed data distribution.

The registry reports a Mixed Model Repeated Measures analysis but does not report its full specification, including the model terms, time points used, covariance structure, or missing-data assumptions. The sponsor analysis therefore cannot be independently reproduced from the posted summary statistics. The unadjusted recalculation is a different analysis and should not be treated as a reproduction of the sponsor’s model.

The clinical interpretation of the score difference is also limited because a threshold for a clinically important change is not reported in the registry record. Nor are equivalence or noninferiority margins reported. The posted finding therefore cannot establish whether a particular difference is meaningful to participants or whether the groups are equivalent.

The primary endpoint is at Week 12 (3 months), so the result concerns that assessment time. The registry record does not report longer-term primary outcome results in the information available for this comparison. It lists two secondary outcomes, but their posted results are not included in the primary comparison details. Multiplicity procedures, detailed masking roles, randomization procedures, and the trial’s original sample-size justification are also not reported in the registry record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: COmparing arNi and Ace For Improving Erectile Dysfunction in mEN With reduCed Ejection Fraction Heart Failure — NCT03917459.
• Registry record last updated 2024-02-29; status last verified 2024-02.
• Results first posted 2024-01-08.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

22. Record Summary

NCT03917459 is a completed phase 3 randomized, triple-masked, parallel-group study sponsored by Novartis Pharmaceuticals. It compared LCZ696 (sacubitril/valsartan) with enalapril in men with heart failure with reduced ejection fraction and erectile dysfunction. The registry lists an enrollment of 27 and records the study start as 2019-04-16 and primary completion as 2021-05-25.

The primary endpoint was the IIEF-15 erectile-function score at Week 12 (3 months), with higher scores indicating better outcome. The sponsor’s Mixed Model Repeated Measures analysis reports a treatment difference of 2.9, a 95% confidence interval from -3.29 to 9.01, and p = 0.343. The interval includes zero, leaving substantial uncertainty about the size and direction of the difference.

The posted endpoint summaries include 12 participants in the LCZ696 group and 13 in the enalapril group. The registry also lists changes in sexual-activity frequency and NT-proBNP as secondary outcomes. The original sample-size justification, detailed missing-data methods, multiplicity procedures, and a clinically important score threshold are not reported in the registry record.