Firibastat or Ramipril After Acute Myocardial Infarction for Prevention of Left Ventricular Dysfunction: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Firibastat or Ramipril After Acute Myocardial Infarction for Prevention of Left Ventricular Dysfunction (NCT03715998), a randomized phase 2 study. The primary outcome is Left Ventricular Ejection Fraction Assessed by Cardiac Magnetic Resonance Imaging (CMRI).

2. Clinical Question

The trial was registered as a phase 2 study and is marked completed. The registry describes a 12-week study with four visits. Its brief summary says 294 subjects would be randomized, while the enrollment field lists 295. Those entries describe different record fields and are not reconciled in the registry record. The results describe 72, 77 and 80 participants in the three primary-outcome groups, respectively; the registry record does not explain how those analysis counts relate to enrollment or to the summary's planned randomization total.

3. Trial Design

This was a randomized, parallel-group, active-controlled phase 2 study. The registry classifies the masking as quadruple, while the brief summary describes the study as double-blind. The record does not explain the difference between those masking descriptions. The three groups were firibastat 100 mg, firibastat 500 mg and ramipril 5 mg, using dose titration during the study. The trial was multicenter according to the brief summary.

The study evaluated oral twice-daily administration over 12 weeks after acute anterior MI. Each active regimen began at a lower dose for 2 weeks and continued at the higher dose for 10 weeks. The primary endpoint was change from baseline in LVEF on Day 84, measured by CMRI. The registry gives a mean and standard deviation for each group, alongside pairwise mean differences and confidence intervals.

The record lists 295 participants enrolled, a start date of 2019-06-04, a primary completion date of 2021-07-08 and a completed status. Those are registry entries; the posted outcome summaries report smaller group-specific counts for the primary endpoint. The record does not report the number screened, the number who completed follow-up, or a participant flow accounting for these counts. It also does not report details of randomization sequence generation, allocation concealment, site-level enrollment, or how treatment masking was maintained.

In general, random assignment is intended to balance prognostic factors across comparison groups, while an active control asks how the study regimens compare with an existing active regimen. A parallel design assigns participants to one group rather than having each participant receive multiple regimens in sequence. These design features describe the intended comparison, but they do not by themselves establish the quality of implementation or remove uncertainty from the estimates.

The original sample-size justification, target power, assumed effect, and the trial's prespecified statistical analysis plan are not reported in the registry record. Likewise, details of planned interim analyses, the primary analysis population, and the handling of missing outcome measurements are not reported in the registry record. The separate planning illustrations are based on observed results and should not be read as the original trial design rationale.

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.

Overall Study

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.

6. Primary Endpoint

The registry lists the primary outcome as Left Ventricular Ejection Fraction Assessed by Cardiac Magnetic Resonance Imaging (CMRI), measured over 84 days.

The primary endpoint is the change from baseline in left ventricular ejection fraction assessed by cardiac magnetic resonance imaging at Day 84. LVEF is a measure describing the fraction of left ventricular volume ejected with each contraction. The registry reports the outcome as a mean, with standard deviation, in a unit described as percentage of left ventricular volumes. The posted group means are changes from baseline, not the participants' absolute LVEF values at Day 84.

In general, a change-from-baseline endpoint evaluates how a measure shifts over follow-up relative to its starting value. A group mean gives the average change for participants included in that outcome summary; the standard deviation describes the spread of participant values around that average. Neither quantity alone describes the distribution's full shape or the experience of every participant.

LVEF is used in this study as a measure of left ventricular function after acute MI. CMRI is the stated assessment method. The registry's primary question is a comparison among two firibastat dose schedules and ramipril, not merely whether each group changed from its own baseline. The comparisons therefore focus on differences between group mean changes. The record does not report the baseline LVEF values, the precise calculation convention for change, or additional details about image acquisition and interpretation.

The endpoint is a measurement outcome rather than a direct count of clinical events. The registry also lists clinical and imaging outcomes as secondary measures, but those do not replace the designated primary endpoint. A difference in a mean imaging measure should be interpreted as evidence about that measure and its precision; it does not, by itself, establish a difference in clinical outcomes or explain the mechanism behind any observed group pattern.

7. Results Posted in the Registry

• Group 2: Firibastat 500 mg: mean 5.30 versus 5.60 on control; difference -0.30 (95% CI -0.67 to 0.07), standardized effect d = -0.26; z-test p = 0.112.
• Group 3: Ramipril 5 mg: mean 5.70 versus 5.60 on control; difference 0.10 (95% CI -0.27 to 0.47), standardized effect d = 0.09; z-test p = 0.594.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Left-ventricle End-diastolic Volume Assessed by CMRI

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Group 2: Firibastat 500 mg: mean 12.70 versus 14.20 on control; difference -1.50 (95% CI -2.92 to -0.08), standardized effect d = -0.34; z-test p = 0.038.
  • Group 3: Ramipril 5 mg: mean 9.40 versus 14.20 on control; difference -4.80 (95% CI -6.22 to -3.38), standardized effect d = -1.08; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Group 2: Firibastat 500 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Group 3: Ramipril 5 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Left-ventricle End-systolic Volume Assessed by CMRI

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Group 2: Firibastat 500 mg: mean -0.40 versus -0.50 on control; difference 0.10 (95% CI -0.94 to 1.14), standardized effect d = 0.03; z-test p = 0.851.
  • Group 3: Ramipril 5 mg: mean -3.10 versus -0.50 on control; difference -2.60 (95% CI -3.64 to -1.56), standardized effect d = -0.80; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Group 2: Firibastat 500 mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Group 3: Ramipril 5 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

N-terminal Pro B-type Natriuretic Peptide (NT proBNP)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Group 2: Firibastat 500 mg: mean -1,596 versus -1,619 on control; difference 22.30 (95% CI -578.62 to 623.22), standardized effect d = 0.01; z-test p = 0.942.
  • Group 3: Ramipril 5 mg: mean -1,736 versus -1,619 on control; difference -116.90 (95% CI -718.37 to 484.57), standardized effect d = -0.06; z-test p = 0.703.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Group 2: Firibastat 500 mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Group 3: Ramipril 5 mg and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes provide a broader view of ventricular remodeling and a biomarker, alongside the primary LVEF measure. The posted numeric results include end-diastolic volume, end-systolic volume and NT-proBNP. Across these measures, the pairwise estimates do not form a uniform pattern: some contrasts are more separated from zero than others, and the confidence intervals vary in width. This overall pattern is relevant as context but does not replace the primary endpoint.

The secondary imaging outcomes are related to cardiac structure and function, while NT-proBNP is a laboratory measure. They may complement the primary measure, but they capture different features and their units and scales are not interchangeable. The posted data do not show that a pattern in one outcome necessarily explains the LVEF result. MACE, described as a combined clinical endpoint of cardiovascular death, MI and cardiac hospitalization, is listed as a secondary outcome, but numeric MACE results are not reported in the registry record.

In general, multiple endpoints and comparisons increase the chance that at least one unadjusted result appears noteworthy by chance, even when no consistent underlying difference exists. The registry record does not report a multiplicity strategy for the secondary outcomes or a hierarchy for interpreting them. That means the secondary p-values should be considered less conclusive than a prespecified, multiplicity-controlled primary analysis. They may motivate questions for further study, but they do not independently establish a broad treatment effect.

There are no sponsor-reported analyses listed for these secondary outcomes. The available summaries do not describe how missing data were handled, whether analyses were adjusted, or whether all outcomes were analyzed in the same population. Consequently, the secondary pattern is best read as descriptive evidence accompanying the primary comparison, with uncertainty about the analysis details and no basis in this record for treating any one secondary result as definitive.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Left-ventricle End-diastolic Volume Assessed by CMRI
• Left-ventricle End-systolic Volume Assessed by CMRI
• Major Cardiac Event (MACE): Combined Clinical Endpoint of Cardiovascular Death, MI, and Cardiac Hospitalization
• N-terminal Pro B-type Natriuretic Peptide (NT proBNP)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: each participant's change in LVEF can take a range of numeric values. The registry reports the mean and standard deviation for each group. A mean is the arithmetic average of the participant measurements included in that group summary. A standard deviation describes how dispersed those measurements are around the mean. In general, a larger standard deviation indicates greater variation among participants, while a smaller one indicates values more concentrated around the mean.

What does a mean difference represent?

The posted mean differences compare each active group with firibastat 100 mg, and also compare firibastat 500 mg with firibastat 100 mg. The sign depends on the order of subtraction used in the comparison: a negative estimate means the second listed group mean is lower than the reference group mean under that convention; a positive estimate means it is higher. The registry identifies the estimates as mean differences. A difference between group means is not the same thing as a within-person change, even though the outcome being compared is itself a change from baseline.

In general, a confidence interval gives a range of values reasonably compatible with the observed data and the statistical model used to construct it. Its width reflects both the amount of information in the data and the variability of the measurements. A narrow interval is more precise than a wide interval, but neither width nor whether an interval includes zero answers the clinical-importance question unless a meaningful threshold is also defined. The registry does not report such a threshold for the primary endpoint.

How should the p-values be read?

A p-value assesses how surprising data at least as incompatible with a specified null model would be if that model were true, under 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 a difference. The posted primary comparisons give unadjusted p-values. The record does not report adjustment for multiple comparisons, so the p-values should not be treated as a single overall test across the study's outcomes and groups.

The arm-level means, standard deviations and counts permit simple unadjusted comparisons of summary statistics. Those calculations do not account for unreported details such as covariate adjustment, stratification, site effects or a repeated-measures model. The registry record does not report whether the sponsor used a different analysis model for the primary endpoint. It also does not provide a sponsor-reported analysis narrative for the primary comparison. No discrepancy flag is recorded for the posted summaries, but that does not supply missing details of the original analysis plan.

Why do standard deviations matter?

The standard deviation contributes to the uncertainty in a group mean and to the uncertainty in a difference between group means. In general, more variable measurements make it harder to estimate a mean difference precisely when the sample sizes are otherwise similar. The posted group standard deviations are close in magnitude for the primary outcome, but the record does not provide individual-level measurements or a distribution plot from which to evaluate skewness, outliers or other features of the data.

For a continuous outcome, a comparison based on group means is most directly informative about average differences. It may not describe differences in spread, unusual values, or subgroups. The registry does not report subgroup analyses or distributional checks. The listed standard deviations summarize spread but do not establish that a normal model is appropriate. Statistical assumptions and diagnostic results for the trial's own analysis are not reported in the registry record.

What can randomization establish?

In general, randomization is used to reduce systematic differences between groups at assignment. It does not guarantee that every measured or unmeasured characteristic is balanced in a particular trial, especially with finite group sizes. The registry labels allocation as randomized but does not report the sequence-generation or concealment methods. The estimate remains subject to sampling uncertainty, measurement issues, missing data and any departures from the intended design.

The registry identifies the trial as parallel-group and active-controlled. Those terms describe the structure of treatment assignment and comparator, rather than a statistical guarantee. The active comparator permits direct comparison with ramipril in the study setting. It does not allow a conclusion about comparison with placebo or no treatment, since no such group is listed.

What is not available about the analysis?

The protocol's primary statistical model, adjustment variables, assumptions, analysis population and missing-data method are not reported in the registry record. Details of interim analyses, multiplicity control, sensitivity analyses and handling of protocol deviations are also not reported. These omissions matter because different prespecified methods can affect the interpretation of an estimate and its uncertainty. The summary-statistic comparisons are useful descriptions of posted results, but they cannot recover the full planned analysis or establish that all design assumptions were met.

The primary comparisons should therefore be read as unadjusted comparisons of reported group summaries, with the confidence intervals indicating their precision under that comparison. The p-values do not quantify clinical importance. Nor do the reported averages show whether individual outcomes cluster tightly around the mean or vary substantially beyond the standard deviation. The clinical context, outcome definition and missing analysis details all constrain how far the numeric summaries can be interpreted.

11. Confidence Intervals and Precision

The primary confidence intervals are useful for judging how precisely the mean differences were estimated. For firibastat 500 mg compared with firibastat 100 mg, the estimated mean difference was -0.3 and the 95% confidence interval ran from -0.670 to 0.070. For ramipril compared with firibastat 100 mg, the estimate was 0.1 and the interval ran from -0.267 to 0.467. Each interval includes zero, so the posted data do not distinguish the corresponding mean difference from zero at the interval's limits.

In general, a confidence interval is not a range containing a known proportion of individual participant values. It describes uncertainty about an estimated quantity under the method's assumptions. The standard deviations describe variability among participant measurements; the intervals describe uncertainty about the group contrasts. These are related but different forms of information.

The intervals allow differences in either direction, and their widths show that the estimates are not exact. Whether the range is narrow enough to rule out an important difference depends on a clinical threshold, which is not reported in the registry record. Thus, an interval that crosses zero is not proof of no difference, and an interval that excludes zero would not by itself establish clinical importance.

Precision also depends on which participants contributed outcome data and how missing values were handled. The registry reports group counts for the outcome but does not report a full participant flow or missing-data analysis. The confidence intervals should be understood as describing uncertainty for the reported comparisons, not as resolving uncertainty about representativeness, missing measurements, or the full analysis plan.

12. 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 sample-size illustrations give participants per arm for 80% power and participants per arm for 90% power. These are not total event counts: the outcomes used for these illustrations are continuous. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set at the stated fraction of the observed effect. The original trial's own sample-size assumptions and justification are not reported in the registry record.

In plain language, the 80% power column gives the illustrated number of participants per group for a design with an 80% chance of detecting the specified effect under the stated assumptions, if that effect and the model assumptions hold. The 90% power column uses a higher chance of detection and therefore generally calls for more participants per group. These are planning illustrations based on observed differences, not observed power for the completed trial.

Rows that use 75% or 50% of the observed effect represent smaller target differences than the row using 100% of the observed effect. Smaller effects are harder to distinguish from random variation, so they require more participants to reach the same planned power under the same assumptions. The numbers can change substantially depending on the endpoint and comparison because observed effects and variability differ.

For example, in the primary comparison of ramipril with firibastat 100 mg, the illustration at 100% of the observed effect gives 2,071 participants per arm for 80% power and 2,772 for 90% power. The much larger figures for smaller fractions illustrate the sensitivity of planning numbers to the target effect. They are not evidence that the trial had, or lacked, a particular probability of finding a result. They are hypothetical planning calculations and should not be mistaken for the trial's original design calculations.

13. 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 = -0.300; pooled standard deviation σ = 1.149.
2. n = 2 × (1.96 + 0.842)² × 1.149² / -0.300² = 230.4, rounded up to 231 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 <- -0.3                      # observed difference in means
sigma <- 1.14938611239833                     # 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(3715998)
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 = 231 (80% power), 309 (90% power)
 75% of observed effect: n per arm = 410 (80% power), 549 (90% power)
 50% of observed effect: n per arm = 922 (80% power), 1,234 (90% power)
power.t.test: 231.4 
Simulated power at n = 231 per arm: 0.802 (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.

14. Multiplicity, Missing Data and Analysis Populations

The study includes a primary outcome, multiple treatment-group comparisons and several secondary outcomes. In general, when many hypotheses are tested, the chance of at least one apparently notable result can increase. A multiplicity plan can control how the evidence is interpreted across comparisons, for example by specifying a testing sequence or adjusting significance thresholds. Such a plan is not reported in the registry record. The posted p-values are unadjusted, so they should be interpreted as individual-comparison results rather than as a controlled family of tests.

The registry does not report a detailed statistical analysis plan, a primary model, covariate adjustments, or a hierarchy among secondary outcomes. It also does not report interim analyses or stopping rules. Without those details, it is not possible to determine from the registry record whether the posted analyses followed a prespecified approach or how the sponsor intended to handle multiple comparisons.

Missing-data methods are also not reported in the registry record. The outcome summaries give group counts, but the record does not provide a complete account of randomized participants, participants with an observed Day 84 outcome, withdrawals, or reasons for missing measurements. It does not state whether missing outcomes were imputed, handled through a model, or excluded from the summary. This limits interpretation because the reported estimates may represent participants with available outcome measurements rather than every randomized participant.

The registry record does not identify an intention-to-treat, per-protocol or other primary analysis population. It does not report sensitivity analyses that might show how conclusions change under alternative assumptions about missing data or protocol deviations. These omissions do not mean that such methods were absent from the full study conduct; they mean the registry record does not document them. Interpretation should remain tied to the posted summaries and should not assume unreported safeguards or adjustments.

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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: chest pain or chest discomfort (non cardiac) (3.1%), covid19 (3.1%), anemia (2.0%), cardiac failure (2.0%), coronary artery disease (2.0%).

The serious adverse event summaries list 98 participants at risk in each group. The numbers affected by serious adverse events were 11 in the firibastat 100 mg group, 18 in the firibastat 500 mg group and 10 in the ramipril group. The listed deaths were 2, 1 and 1, respectively. The other adverse event summaries list 43, 54 and 54 participants affected in the same group order. These counts are descriptive and do not establish that an event was caused by a study regimen.

The registry lists serious-event terms including chest pain or chest discomfort (non cardiac) and COVID19 at 3.1% each, and anemia, cardiac failure, coronary artery disease and acute kidney injury at 2.0% each. These term-level entries do not, on their own, show comparative risk or severity for an individual participant. The registry record does not provide event timing, exposure-adjusted rates, relatedness assessments, or a statistical comparison of safety between groups.

For safety interpretation, denominators and definitions matter. The at-risk counts are those listed for the adverse-event summaries and should not be replaced by the enrollment field. The registry does not provide a full explanation of how adverse events were collected or adjudicated. The counts are therefore a record-level description, not a basis for concluding that one regimen is safer.

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

The primary results describe average changes in LVEF at Day 84 among the participants represented in the posted group summaries. The estimated differences are close to zero relative to their uncertainty, and both primary confidence intervals include zero. The evidence is therefore inconclusive about whether the group means differed by a nonzero amount; it is not proof that the groups were identical.

The registry record does not identify a threshold for a clinically important LVEF difference, nor does it describe an equivalence or noninferiority objective. Without such a framework, absence of a statistically compelling difference cannot be reinterpreted as equivalence. The findings also do not establish effects beyond the measured endpoint and follow-up period. The study's primary assessment was at Day 84.

The outcome is a cardiac imaging measure, not a direct measure of survival, symptoms or hospitalization. Although the registry lists MACE as a secondary outcome, numeric MACE results are not reported in the registry record. As a result, the primary measurement alone cannot answer whether clinical event rates differed. It also cannot establish how an individual participant might respond or whether the average change applies equally across subgroups.

The study compares two firibastat dose schedules with an active ramipril regimen in a specific post-MI study population. It does not compare either drug with no active treatment. The registry record does not provide enough detail to judge broader applicability beyond the stated population and trial setting, or to assess long-term outcomes. Interpretation should therefore remain limited to the posted group summaries and their uncertainty, without converting them into a recommendation or a general claim about treatment effect.

17. Why This Trial Matters Statistically

This trial illustrates why the size and precision of an estimate matter alongside its p-value. The primary comparisons have estimated mean differences near zero and confidence intervals that cross zero, but the intervals still permit values on either side. Reading only a p-value would omit the range of differences compatible with the data; reading only the point estimate would hide its uncertainty.

It also shows how an active-controlled design shapes the question. The comparison is between firibastat dose schedules and ramipril, rather than against no treatment. This determines what the randomized contrast can answer. The parallel-group design and randomized allocation support a direct group comparison in principle, while incomplete reporting of the analysis plan and missing-data methods constrains how fully that comparison can be evaluated from the registry record.

The secondary outcomes reinforce the importance of distinguishing a primary question from multiple supporting measures. Related endpoints can provide context, but unadjusted results across several comparisons carry a greater risk of chance findings. Numeric results for MACE are not reported, which also demonstrates why a list of planned or registered outcomes is not equivalent to posted outcome evidence.

Finally, the planning illustrations make clear that sample-size calculations depend strongly on the effect targeted. A smaller effect requires more participants under the stated assumptions. Such calculations can help readers understand design sensitivity, but observed-effect-based illustrations do not reveal the power the trial actually had at its design stage. The original design assumptions are not reported in the registry record.

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 record leaves several trial-specific uncertainties. It lists enrollment of 295, while the brief summary says 294 subjects would be randomized; the record does not explain the difference. Outcome summaries use counts of 72, 77 and 80, and adverse-event summaries list 98 at risk in each group. The participant flow connecting these figures is not reported in the registry record.

The primary endpoint is described as change from baseline at Day 84, but baseline values and details of the calculation are not reported. The registry does not report the primary statistical model, analysis population, adjustment variables, missing-data handling, sensitivity analyses or multiplicity approach. These omissions limit assessment of whether the posted summary-statistic comparisons match the prespecified analysis.

The record describes masking as quadruple in one field and double-blind in its brief summary, without explaining the difference. It also does not report the randomization sequence method or allocation concealment. These are reporting gaps in the registry record; they do not establish that the procedures were absent from the trial.

Follow-up for the study is described as 12 weeks, and the primary measurement is at Day 84. Longer-term outcome summaries are not reported. Although MACE is listed as a secondary endpoint, its numeric results are not reported in the registry record. The available safety summaries give counts but do not provide event timing, treatment relatedness or comparative statistical analyses. Finally, the study is phase 2, and the record does not report a clinically meaningful threshold for the primary measure or a formal equivalence or noninferiority objective.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Firibastat or Ramipril After Acute Myocardial Infarction for Prevention of Left Ventricular Dysfunction — NCT03715998.
• Registry record last updated 2023-02-27; status last verified 2020-12.
• Results first posted 2023-02-27.
• 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

NCT03715998 is a completed, randomized, parallel-group phase 2 study of firibastat versus ramipril after acute anterior MI. The primary endpoint was mean change from baseline in LVEF assessed by CMRI at Day 84. The posted group means were 5.6, 5.3 and 5.7 for firibastat 100 mg, firibastat 500 mg and ramipril, respectively.

The primary pairwise estimates were -0.3 for firibastat 500 mg versus firibastat 100 mg and 0.1 for ramipril versus firibastat 100 mg. Both confidence intervals include zero. These results do not establish equivalence, and the registry record does not report the original sample-size justification, detailed statistical plan, missing-data methods or multiplicity strategy. Secondary summaries and safety counts add context but do not resolve those limitations.