Patient-reported Outcomes in Vericiguat-treated Patients With HFpEF: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Patient-reported Outcomes in Vericiguat-treated Patients With HFpEF (NCT03547583), a randomized phase 2 study. The primary outcome is Change in KCCQ Physical Limitation Score From Baseline to Week 24.

2. Clinical Question

The question concerns a patient-reported measure of physical limitations associated with heart failure, rather than a direct measure of survival or a clinical event. The KCCQ score is transformed to a 0-100 scale, with higher scores indicating better health status. The posted arm estimates represent mean changes, and the reported comparisons estimate differences between each vericiguat group and placebo.

The results therefore address average change in the selected patient-reported measure among participants meeting the analysis-set requirements. They do not, by themselves, describe every randomized participant or establish how individual participants experienced treatment. The registry record also lists change in the Six-minute Walk Test as a secondary outcome, offering a different measure of physical function.

3. Trial Design

VITALITY-HFpEF was a Phase 2 randomized, parallel-group, placebo-controlled trial of oral vericiguat in patients with heart failure and preserved ejection fraction. The registry record lists quadruple masking, while the official title describes the trial as double-blind. The sponsor was Bayer. The trial is recorded as completed, with enrollment of 789.

The registry record gives a start date of 2018-06-15 and a primary completion date of 2019-10-15. Participants were assigned to one of three groups: vericiguat up to 10 mg, vericiguat up to 15 mg, or placebo. Treatment was planned for 24 weeks. The 10 mg group began at 2.5 mg once daily, increased to 5 mg at Week 2 and 10 mg at Week 4, and had sham titration at Week 6. The 15 mg group followed the same early increases and increased to 15 mg at Week 6. The placebo group received once-daily placebo with sham increases at Weeks 2, 4, and 6.

The primary outcome was change in KCCQ Physical Limitation Score from baseline to Week 24. The registry record describes the measure as a least-squares mean with standard error and specifies the analysis population as randomized and treated participants with observed KCCQ assessments at baseline and after baseline, excluding safety follow-up. A change in Six-minute Walk Test distance from baseline to Week 24 was also posted as a secondary outcome.

The registry record does not report the trial’s original sample-size justification or the assumptions used to plan enrollment. It also does not report enough detail in the record to establish every aspect of treatment adherence, follow-up, or analysis procedures. Those omissions limit what can be concluded about the rationale and implementation beyond the design features explicitly recorded.

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: Overall, 979 participants were screened, of whom 789 participants were randomized in the study. 788 of the randomized participants were allocated to study treatment, of whom 672 participants completed the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: FAS KCCQ: All patients randomized and treated (at least one dose of the study treatment), and had at least one observed KCCQ PLS assessment at both baseline and during post-baseline (excluding safety follow-up) were valid for this analysis set.

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: All participants randomized were valid for the FAS.

6. Primary Endpoint

The registry lists the primary outcome as Change in KCCQ Physical Limitation Score From Baseline to Week 24, measured over From baseline to Week 24.

The primary endpoint was change in KCCQ Physical Limitation Score from baseline to Week 24. The Kansas City Cardiomyopathy Questionnaire measures the impact of heart failure, or its treatment, across six domains: Physical Limitation, Symptom, Quality of Life, Social Limitations, Symptom Stability, and Self-Efficacy. The symptom domain includes frequency and burden subscores.

For this endpoint, the focus is the Physical Limitation domain. Domain responses are summed and transformed to a 0-100 scale. Higher scores indicate better health status. Measuring change from baseline makes the comparison about how scores shifted during follow-up, rather than only comparing Week 24 scores without reference to participants’ starting values.

A patient-reported outcome can capture participants’ perceptions of limitations in daily activities, a dimension that may not be fully represented by clinical events or a walking test. It is useful for studying a treatment question framed around physical functioning in daily life. At the same time, the score is not a direct measure of a specific activity, and the group mean does not describe the full range of individual responses.

The analysis set required a baseline and a post-baseline KCCQ assessment, along with randomization and treatment. Thus, the posted primary estimate pertains to that defined population, not necessarily every participant enrolled or randomized.

7. Results Posted in the Registry

• Vericiguat up to 10 mg: mean 6.41 versus 6.93 on control; difference -0.52 (95% CI -4.85 to 3.81), standardized effect d = -0.02; z-test p = 0.814.
• Vericiguat up to 15 mg: mean 5.47 versus 6.93 on control; difference -1.46 (95% CI -5.72 to 2.80), standardized effect d = -0.06; z-test p = 0.502.

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.

Change in the Six-minute Walk Test (6MWT) From Baseline to Week 24

• 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 errors.
• Result:
  • Vericiguat up to 10 mg: mean 8.68 versus 10.49 on control; difference -1.81 (95% CI -17.55 to 13.93), standardized effect d = -0.02; z-test p = 0.822.
  • Vericiguat up to 15 mg: mean 5.00 versus 10.49 on control; difference -5.49 (95% CI -21.06 to 10.08), standardized effect d = -0.06; z-test p = 0.489.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Vericiguat up to 10 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 Vericiguat up to 15 mg and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary outcome is change in Six-minute Walk Test distance from baseline to Week 24. Its arm estimates and comparisons show a pattern in which the placebo mean change is numerically higher than the mean change in each vericiguat group. The sponsor’s repeated-measures comparisons and the unadjusted recalculations do not indicate a clear separation between either vericiguat group and placebo; the reported confidence intervals include zero.

This overall pattern is consistent with the primary result in the limited sense that neither outcome provides a clear statistical signal of a difference favoring the vericiguat groups in the posted comparisons. The endpoints measure related but distinct aspects of physical function: the KCCQ is patient-reported, while the Six-minute Walk Test records distance walked. Similar broad patterns do not make the measures interchangeable, and one result cannot validate or invalidate the other.

The registry record lists one secondary outcome, but the posted analyses include comparisons for both vericiguat dose groups. The record does not report a multiplicity procedure or establish how the secondary analyses were prioritized. When multiple outcomes, groups, time points, or analyses are considered, unadjusted results can overstate the strength of evidence if they are interpreted as though only one comparison had been made. For that reason, secondary findings without a reported adjustment or prespecified hierarchy should carry less weight than the primary analysis.

The secondary evidence is best treated as supportive context, not as an independent confirmation of a treatment effect. The registry record does not report a prespecified threshold for a meaningful change in walking distance, and statistical estimates alone do not determine whether any observed difference would matter to participants.

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

• Change in the Six-minute Walk Test (6MWT) From Baseline to Week 24

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a score on a scale, and the posted results summarize average change. For a continuous measure, a group mean describes the central level of observed values, while a standard error describes the uncertainty around an estimated mean. The registry record labels the arm estimates as least-squares means and their dispersion as standard errors. A least-squares mean is a model-based estimate of an average; it need not be identical to a raw arithmetic average when a model accounts for features of the data.

The sponsor compared the treatment groups with placebo using a mixed model repeated-measures analysis. In general, a repeated-measures model is designed for outcomes measured repeatedly over follow-up. It can use the pattern of measurements across visits rather than treating every measurement as unrelated. A mixed model can account for within-participant correlation and can estimate group differences over time under the model’s assumptions. The registry record does not describe the full model specification, such as all included terms, covariance structure, or missing-data assumptions, so those details cannot be assessed from the record.

The reported comparison is a difference of least-squares means. It expresses the estimated contrast between a vericiguat group and placebo, in the same units as the outcome. A value below zero means the modeled change was lower in the vericiguat group than in placebo; a value above zero would indicate a higher modeled change. The estimate is accompanied by a confidence interval to convey its statistical uncertainty.

The posted recalculations use the displayed arm means and standard errors to form simple, unadjusted comparisons. They are not the sponsor’s repeated-measures model. In these recalculations, the standard deviations used to characterize variability are approximate, as indicated in the calculation record. The recalculated confidence intervals and p-values can consequently differ from the sponsor’s model-based values. Recalculations are useful as a check on the direction and broad scale of the comparisons, but they do not reproduce the sponsor’s analysis.

A p-value is a measure of how compatible the observed data are with a specified null hypothesis under the analysis model. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. An unadjusted p-value also does not account for testing multiple outcomes or comparisons. The registry record does not report whether or how multiplicity was addressed, so the posted p-values should not be treated as adjusted evidence across all analyses.

A confidence interval gives a range of estimates compatible with the data and the model at its stated confidence level. In general, a narrower interval indicates greater precision, while a wider interval indicates more uncertainty. An interval containing zero for a difference means that a zero difference is among the values compatible with the estimate at that confidence level; it does not prove that the true difference is zero.

Over-dispersion is a general concern when data vary more than a chosen model assumes. If a model understates variability, standard errors may be too small and intervals may be too narrow. The endpoint is a continuous score, and the registry record does not report a diagnosis of over-dispersion or the specific diagnostic checks used. It would therefore be inappropriate to claim that over-dispersion occurred or was ruled out.

The primary analysis population is defined as the FAS KCCQ group: randomized and treated participants who had observed KCCQ Physical Limitation Score assessments at baseline and at least one post-baseline assessment, excluding safety follow-up. This definition requires outcome data at both baseline and after baseline. The number excluded from the analysis for not meeting these criteria, and the methods used to handle missing outcome measurements, are not reported in the registry record.

The secondary walking-test comparisons are also posted as least-squares mean estimates with standard errors and sponsor repeated-measures results. The same distinction applies: the sponsor analysis is model-based, while the simple recalculations use posted arm summaries. Neither the unadjusted recalculation nor a single p-value should be read as a complete account of the trial’s statistical plan. The original plan for analysis, including prespecified handling of multiple comparisons, is not reported in the registry record.

11. Confidence Intervals and Precision

The sponsor reported 97.5% confidence intervals for the primary comparisons. For vericiguat up to 10 mg versus placebo, the estimated difference was -0.52, with an interval from -5.17 to 4.13. For vericiguat up to 15 mg versus placebo, the estimate was -1.46, with an interval from -6.02 to 3.10. Both intervals include zero and span values in both directions.

These intervals show that the observed estimates are not highly precise in the sense of narrowing the plausible range to a single direction or a small set of values. The data are compatible with modestly lower average changes in the vericiguat groups, and also with higher changes. The interval limits should not be interpreted as guaranteed boundaries for the true effect. They describe uncertainty under the model and its assumptions.

The confidence level reported by the sponsor is 97.5%. The registry record does not explain why that level was used or how it relates to any planned adjustment for multiple comparisons. The recalculated intervals use a different, unadjusted approach and are not interchangeable with the sponsor’s intervals. For example, the recalculated intervals for the primary comparisons are -4.854 to 3.814 and -5.719 to 2.799. The differences between the two sets reflect distinct methods and should not be resolved by choosing whichever interval appears more favorable.

Precision is not the same as importance. Even a precise estimate would need clinical context to determine whether its magnitude matters to patients; conversely, a potentially important estimate may remain uncertain if its interval is wide. The registry record does not state a threshold for a clinically important difference on this endpoint.

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 figures are planning illustrations based on the observed effect, not the trial’s original design assumptions. For these continuous outcomes, the figures are participants per arm. The general assumptions listed for the illustrations 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 to the stated fraction of the observed effect. The registry record does not report the assumptions behind the trial’s original enrollment plan.

The 80% power column gives the number of participants per arm that the illustration estimates would be needed for an 80% chance of detecting the chosen effect under those assumptions, if that effect were present. The 90% power column gives the corresponding number per arm for a 90% chance. Power is a feature of a planned design under specified assumptions; it is not a measure of how likely the observed result is to be true.

Rows planning for 75% or 50% of the observed effect use smaller effects than the row using 100% of the observed effect. Smaller effects are harder to distinguish from random variation, so the illustrations require more participants per arm to reach the stated power levels. The effect fractions are planning scenarios, not claims that those effects are clinically meaningful or likely to occur.

These figures are not observed power. They do not describe the probability that the completed trial’s result is correct, and they should not be used to reinterpret the observed confidence intervals as if the trial had been designed around the recalculated effect. The illustrations also do not substitute for a prospective sample-size justification based on a prespecified target effect and the trial’s original analysis plan.

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 = -0.520; pooled standard deviation σ = 24.877.
2. n = 2 × (1.96 + 0.842)² × 24.877² / -0.520² = 35,927.2, rounded up to 35,928 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 <- -0.52                      # observed difference in means
sigma <- 24.8769060555533                     # 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(3547583)
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 = 35,928 (80% power), 48,097 (90% power)
 75% of observed effect: n per arm = 63,871 (80% power), 85,505 (90% power)
 50% of observed effect: n per arm = 143,709 (80% power), 192,386 (90% power)
power.t.test: 35928.2 
Simulated power at n = 35,928 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.

14. Analyses Reported by the Sponsor

The sponsor’s primary analyses used a mixed model repeated-measures method and reported differences of least-squares means. For vericiguat up to 10 mg versus placebo, the estimate was -0.52, with a 97.5% confidence interval from -5.17 to 4.13. For vericiguat up to 15 mg versus placebo, the estimate was -1.46, with a 97.5% confidence interval from -6.02 to 3.10.

The simple recalculations from the posted summary statistics produce the same estimated differences, with confidence intervals of -4.854 to 3.814 and -5.719 to 2.799. Their unadjusted p-values are 0.814 and 0.502. The recalculations approximate variability from the arm-level standard errors and do not reproduce the sponsor’s repeated-measures model. The sponsor’s model-based analyses are the primary record of the sponsor’s statistical comparisons.

The two approaches tell a broadly similar story in direction and uncertainty: both estimated differences are negative, and the confidence intervals include zero. Their numerical intervals and p-values differ because the methods are not identical. The registry record does not report a discrepancy between the posted sponsor analyses and the recalculations. Neither approach establishes equivalence or rules out smaller effects.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several statistical comparisons are conducted, because considering many results can increase the chance of finding at least one apparently notable result even when no true effect exists. The primary outcome has two dose-group comparisons with placebo, and the record also includes a secondary walking-test outcome. The registry record does not report whether the trial used a multiplicity adjustment, a hierarchical testing sequence, or another method to control interpretation across analyses.

The sponsor reports 97.5% confidence intervals for the primary comparisons. The record does not explain the rationale for that confidence level or say whether it was part of a multiplicity strategy. It would be speculative to infer the trial’s intended error control from the confidence level alone. The unadjusted recalculated p-values likewise do not account for multiple comparisons.

Missing outcome data are relevant because the primary analysis set required KCCQ observations at baseline and after baseline. The registry record describes this requirement but does not report the number of randomized participants who lacked qualifying assessments, the reasons for missingness, or the method used to handle incomplete repeated measurements in the sponsor’s model. It also does not report sensitivity analyses evaluating alternative assumptions about missing data. Without those details, the possible influence of missingness cannot be fully assessed.

The registry record identifies the primary analysis population as randomized and treated participants who met the KCCQ assessment requirements. It does not report whether an intention-to-treat analysis of all randomized participants was also conducted, or how other analysis populations were defined. The posted arm counts for the primary analysis are not the same as the total enrollment, and should be read in light of the endpoint-specific population definition rather than as a count of everyone enrolled.

The sample-size rationale and original analysis plan are also not reported in the registry record. Consequently, it is not possible to assess from the record whether the trial was planned around a particular clinically important difference, how multiplicity was intended to be handled, or which missing-data assumptions were prespecified.

16. 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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (2.7%), atrial fibrillation (1.5%), acute kidney injury (1.5%), hypotension (1.5%), chronic obstructive pulmonary disease (1.5%).

The registry safety summary lists serious adverse events among 262 participants at risk in the vericiguat up to 10 mg group, 264 in the up to 15 mg group, and 262 in the placebo group. The numbers affected were 46, 54, and 48, respectively. Other adverse events were recorded among the same group denominators, with 121, 134, and 131 participants affected. The summary also records 15, 10, and 7 deaths in the respective groups.

These are descriptive counts from the safety summary. They do not by themselves establish that treatment caused an event or death, and they do not account for differences in event timing or duration of exposure. The registry record does not provide enough detail to characterize event severity beyond the serious-adverse-event classification, compare specific risk measures, or determine causes of death.

The most frequently listed serious-event terms include pneumonia at 2.7%, and atrial fibrillation, acute kidney injury, hypotension, and chronic obstructive pulmonary disease at 1.5% each. Anaemia is listed at 1.1%. These listed percentages describe terms in the posted summary; they should not be interpreted as a complete safety profile or as proof of a treatment-related effect. Safety interpretation requires the event definitions, clinical context, timing, and appropriate comparative analysis.

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

The primary result describes average change in a patient-reported physical-limitation score over 24 weeks among participants meeting the stated analysis-set criteria. The estimated differences between each vericiguat group and placebo were small relative to the uncertainty represented by the confidence intervals, and the intervals included zero. The sponsor’s model-based tests did not provide evidence of a statistically significant difference at the conventional 0.05 threshold.

This does not establish that the treatments and placebo have identical effects. A confidence interval containing zero can also contain nonzero effects in either direction. The results therefore do not rule out every possible difference, and they do not establish equivalence or non-inferiority. Such conclusions require an appropriate design, prespecified margins, and analyses that are not reported in the registry record.

The result also does not show what happened to every participant. Mean changes can conceal variation in individual responses, and the primary analysis included only participants with the required observed KCCQ assessments. The record does not report the full pattern of missing outcome data or the analyses needed to assess how missingness may have affected the estimates.

Statistical significance is not the same as clinical importance. The registry record does not report a threshold for a clinically meaningful change in KCCQ Physical Limitation Score. Consequently, the estimates and intervals can describe statistical uncertainty, but cannot on their own determine the importance of a possible difference to patients.

Finally, the endpoint addresses one aspect of health status and does not stand in for every outcome that might matter in heart failure. The posted walking-test outcome is distinct, and the registry record’s safety counts are descriptive. The evidence should be read within those boundaries, rather than as a complete account of all potential benefits and harms.

18. Why This Trial Matters Statistically

This trial is statistically informative because it compares two vericiguat target-dose strategies with placebo using a patient-reported measure tied to physical limitations. The design is randomized and parallel-group, and the primary outcome is explicitly defined as change from baseline to Week 24. Those features make the intended contrast and measurement window clear.

The results also illustrate why an estimated mean difference should be read together with its confidence interval. The primary estimates are negative, but their intervals include zero and extend across values in both directions. A point estimate alone would conceal that uncertainty, while a nonsignificant p-value alone would not communicate the range of effects compatible with the data.

The sponsor’s repeated-measures analyses and simple recalculations from posted summary statistics offer different statistical summaries of the same broad comparison. Their estimates align, while their intervals and p-values differ because the underlying methods differ. This is a useful reminder that a recalculation is not a substitute for the trial’s model-based analysis, particularly when the full model specification is not reported.

The record also makes the analysis population consequential: the primary outcome population required observed baseline and post-baseline measurements. Assessment of missingness, multiplicity, and the original sample-size rationale is limited because these details are not reported. These are not minor technicalities; they affect how confidently the results can be generalized and how the full collection of analyses should be interpreted.

Overall, the trial provides a defined comparison and transparent endpoint-level estimates, while leaving important planning and analysis details unavailable in the registry record. Keeping the estimate, uncertainty, analysis population, and reporting gaps in view is essential to a balanced statistical reading.

19. 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 primary result applies to the defined KCCQ analysis population, not automatically to all 789 enrolled participants. The analysis required participants to be randomized and treated and to have observed assessments both at baseline and after baseline. The number who did not meet those criteria and the reasons for any missing assessments are not reported in the registry record.

The record does not report the full specification of the sponsor’s mixed model repeated-measures analysis. Details such as model terms, covariance assumptions, and missing-data handling are therefore unavailable for independent assessment. The reported sponsor intervals and p-values can be described, but the record does not permit a full reconstruction of the model.

The confidence intervals for the primary comparisons include zero and allow values in either direction. The record does not provide a clinically important difference threshold for the KCCQ Physical Limitation Score. As a result, statistical uncertainty can be described, but clinical importance cannot be established from the posted estimates alone.

The simple recalculations rely on approximate variability derived from the posted standard errors and do not reproduce the sponsor’s repeated-measures approach. They should be viewed as supplementary, unadjusted comparisons. The record also does not report whether the analyses accounted for multiple comparisons, or whether a prespecified testing hierarchy was used.

The trial’s original sample-size justification and statistical analysis plan are not reported in the registry record. The planning illustrations based on observed effects cannot fill that gap. The record also provides limited safety detail for judging event timing, exposure, attribution, and causes of death. These limitations constrain interpretation without establishing that the trial’s conduct or analyses were inadequate.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Patient-reported Outcomes in Vericiguat-treated Patients With HFpEF — NCT03547583.
• Registry record last updated 2021-01-06; status last verified 2020-11.
• Results first posted 2020-12-03.
• 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.

23. Record Summary

VITALITY-HFpEF was a completed Phase 2 randomized, parallel-group, placebo-controlled trial sponsored by Bayer, with enrollment of 789. It evaluated vericiguat up to 10 mg and up to 15 mg against placebo over 24 weeks in patients with chronic heart failure with preserved ejection fraction.

The primary outcome was change in KCCQ Physical Limitation Score from baseline to Week 24. Sponsor-reported differences of least-squares means were -0.52 and -1.46 for the two vericiguat comparisons with placebo; both reported 97.5% confidence intervals included zero. The record also includes a secondary Six-minute Walk Test outcome and descriptive safety counts.

The registry record does not report the original sample-size rationale, the complete analysis plan, the multiplicity approach, or detailed missing-data handling. These omissions limit assessment of planning and some aspects of statistical interpretation.