This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for The Effect of Vericiguat on Peripheral Vascular Function, Patient Health Status and Inflammation (NCT05420012), a randomized phase 4 study. The primary outcome is Flow-Mediated Dilation (FMD).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT05420012 |
| Phase | Phase 4 |
| Condition | Heart Failure, Heart Failure With Reduced Ejection Fraction (HFrEF) |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 26 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Josef Stehlik |
| Results posted | Yes |
2. Clinical Question
Population
People with heart failure with reduced ejection fraction (HFrEF). The registry record describes an enrollment of 26, but further details about participant characteristics are not reported in the registry record.
Intervention
Vericiguat, listed as the study drug. The registry record does not report the dose or a detailed dosing schedule.
Comparator
Placebo, listed as the comparator. Further details about its administration are not reported in the registry record.
Primary question
Does flow-mediated dilation (FMD), a measure of peripheral vascular function, change from baseline to 12 weeks in the study comparing vericiguat with placebo? The registry record identifies this endpoint but does not report its results.
The study asks whether vericiguat is associated with a change in peripheral vascular function in people with HFrEF. FMD is measured as the maximal change in brachial artery diameter after cuff release, expressed as a percentage increase from the pre-occlusion value. The endpoint therefore concerns a physiological measure rather than a direct measure of symptoms, daily functioning, or clinical events.
The study also aims to examine inflammatory status and patient health status. The listed secondary outcomes include the Six-minute Walk Test (6MWT), Kansas City Cardiomyopathy Questionnaire-12 (KCCQ12), Visual Analogue Scale (VAS), and serum Interleukin-18 (IL-18) and Interleukin-6 (IL-6). The brief summary additionally describes an aim to identify patients more likely to benefit, based on baseline peripheral vascular dysfunction and a high inflammatory state. Whether that aim was evaluated, and how any subgroup or predictive analysis was specified, is not reported in the registry record.
The record describes the study question and outcomes, but it does not provide outcome estimates or statistical comparisons. Thus, the clinical question can be stated from the registered aims, while the direction and precision of the observed FMD result cannot be assessed from the posted results.
3. Trial Design
This is a phase 4, randomized, double-masked, parallel study comparing vericiguat with placebo. The registry record lists 26 participants as the enrollment. Randomization indicates that assignment was intended to use a chance-based process; double masking indicates that the record describes masking for two parties, but it does not identify those parties or provide further details about how masking was maintained. The parallel model means the assigned groups are compared over the study rather than participants being described as crossing between treatments.
The primary endpoint is change in FMD from baseline to 12 weeks. FMD is summarized using a mean and standard deviation in the endpoint description. The registry record lists the timeframe as baseline to 12 weeks, but it does not provide the visit schedule, the timing of other outcome assessments, or the procedures used to collect measurements.
The listed secondary outcomes cover exercise capacity, reported health status, a visual analogue measure, and inflammatory biomarkers. The study description also states an interest in identifying participants who may be more likely to benefit based on baseline vascular function and inflammation. The statistical methods for the secondary outcomes and any assessment of treatment-effect variation are not reported in the registry record.
The status is completed. The record lists a start date of 2023-05-01 and a primary completion date of 2024-10-24. These dates describe the registered study timeline; they do not supply outcome findings. The sponsor is listed as Josef Stehlik.
Enrollment does not, by itself, establish how many participants contributed data to each endpoint. The adverse-event record lists participants at risk separately by group, but analysis populations, endpoint-specific sample sizes, withdrawals, and the handling of missing observations are not reported in the registry record. The registry record also does not report the randomization procedure, allocation concealment details, or a statistical analysis plan. These omissions limit how fully the design and conduct can be evaluated from the public 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.
Overall Study
| Stage | Vericiguat | Placebo |
|---|---|---|
| STARTED | 13 | 13 |
| COMPLETED | 13 | 12 |
| NOT COMPLETED | 0 | 1 |
Reasons for not completing this period:
| Reason | Vericiguat | Placebo |
|---|---|---|
| Lost to Follow-up | 0 | 1 |
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.
| Characteristic | Unit | Vericiguat | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 13 | 12 | 25 | |
| Age, Continuous | years | 68 (52 to 79) | 67 (59 to 71) | 67 (57 to 73) |
| Sex: Female, Male: Female | Participants | 3 | 1 | 4 |
| Sex: Female, Male: Male | Participants | 10 | 11 | 21 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 12 | 12 | 24 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 13 | 12 | 25 |
| New York Heart Association Class II | Participants | 11 | 8 | 19 |
| New York Heart Association Class III | Participants | 2 | 4 | 6 |
| Systolic Blood Pressure (mmHg) | mmHg | 112 (106 to 126) | 99 (91 to 122) | 109 (97 to 124) |
| Diastolic Blood Pressure (mmHg) | mmHg | 75 (67 to 79) | 70 (62 to 75) | 71 (63 to 76) |
| Body Mass Index (Kg/m^2) | Kg/m^2 | 29.3 (26.7 to 34.5) | 30.9 (29.6 to 34.0) | 30.8 (28.8 to 34.5) |
6. Primary Endpoint
The registry lists the primary outcome as Flow-Mediated Dilation (FMD), measured over Baseline to 12 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | % increase from pre-occlusion value |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is flow-mediated dilation (FMD), reported as change in vascular function from baseline to 12 weeks. The registry record defines FMD as the maximal change in brachial artery diameter following cuff release, expressed as a percentage increase from the pre-occlusion value. The measurement is intended to capture a vascular response under a standardized physical stimulus and is used as a measure of peripheral vascular function.
As a continuous endpoint, FMD can be summarized by a mean and a measure of variability. The registry record specifies the mean and standard deviation. The mean describes the average observed measurement or change within a group; the standard deviation describes how spread out individual values are around that average. Neither summary alone describes the uncertainty in a comparison between treatment groups.
In general, a change-from-baseline endpoint considers how the measurement changes over the stated follow-up period. A treatment comparison is most directly interpreted through the difference in change between groups, rather than by treating a within-group change as evidence of a treatment effect. The registry record does not report the group-level FMD changes, a between-group contrast, a confidence interval, or a significance test. It therefore does not establish the size, direction, or precision of an observed treatment-group difference.
FMD is a physiological outcome, not a direct measure of symptoms or clinical events. The registry record lists additional health-status, exercise, and inflammatory outcomes, but their results are also not reported in the registry record. How these outcomes relate to the primary endpoint in the analysis is not specified.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies FMD change from baseline to 12 weeks as the primary endpoint, but it does not report the numerical outcome results. There is no posted group mean change, treatment contrast, standard error, confidence interval, or p-value for the primary endpoint. As a result, the magnitude and direction of the observed FMD comparison cannot be described from this record, and its precision cannot be evaluated.
The record lists six outcome measures and names secondary outcomes covering walking capacity, health status, a visual analogue scale, and inflammatory biomarkers. It does not provide the results for those outcomes. The number of analyses recorded is zero. This means that no analysis results are listed in the registry record; it does not establish whether analyses were conducted outside the record or what their findings were.
Interpretation of a continuous outcome ordinarily depends on both the estimated group contrast and its uncertainty. A confidence interval communicates a range of values compatible with the data and analysis, under the assumptions used to construct it. A p-value addresses compatibility with a specified null hypothesis under a statistical model; it does not describe the size or clinical importance of an effect. Neither type of result is reported for FMD in the registry record. The endpoint description’s use of a mean and standard deviation does not substitute for an estimate of the between-group contrast or its uncertainty.
The brief summary describes a rationale involving soluble guanylate cyclase, cyclic guanosine monophosphate, inflammation, oxidative stress, endothelial dysfunction, and nitric oxide bioavailability. This is the stated scientific motivation for examining vericiguat and vascular function. It is not an outcome finding. Likewise, the stated aim of identifying participants who might be more likely to benefit does not show that such a subgroup was identified. The subgroup definition, statistical test, and results are not reported in the registry record.
Safety information is reported as counts of participants at risk and participants affected. In the vericiguat group, the record lists 3 participants affected by serious adverse events and 5 affected by other adverse events, with 0 deaths. In the placebo group, it lists 1 participant affected by serious adverse events and 6 affected by other adverse events, with 0 deaths. These are descriptive counts. The record does not provide event-level detail for the listed affected participants, statistical comparisons, or information sufficient to attribute an event to treatment.
The planning assumptions described in the registry record concern sample-size illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such planning calculations are not observed power and do not replace a reported treatment estimate. The numerical illustrations and the observed primary effect are not reported in the registry record. Without outcome estimates and their uncertainty, the posted record supports a description of the study design and intended endpoints, but not a quantitative conclusion about the primary comparison.
9. Statistical Methods Explained
The statistical methods used to analyze the clinical outcomes are not reported in the registry record. The endpoint description says FMD is a continuous measure summarized by a mean and standard deviation, but it does not state how the treatment groups were compared. The explanations below describe general statistical concepts, not methods confirmed as having been used in this study.
What does a mean and standard deviation describe?
In general, a mean summarizes the center of a set of measurements. A standard deviation describes the dispersion of individual observations around that mean. These summaries help describe the data within a group, but they do not by themselves answer whether the groups differ. To assess a treatment comparison, an analysis must estimate a contrast between groups and quantify uncertainty around that estimate.
For a change-from-baseline outcome, a group’s average change describes the average difference between follow-up and baseline measurements for that group. A comparison of those group changes asks whether the change differs between the randomized groups. It is important not to confuse a change within one group with the comparative effect: improvement or decline in a group alone does not establish that the groups changed differently. The registry record does not state whether the analysis compared changes, adjusted for baseline values, or used another approach.
What would a confidence interval add?
In general, a confidence interval expresses the uncertainty around an estimated quantity under the assumptions of the analysis. For a treatment comparison, it can show both the estimated direction and the range of effect sizes compatible with the data and model. A narrow interval indicates greater statistical precision than a wide interval, all else equal. A confidence interval does not resolve questions about bias, measurement quality, or whether an effect matters to patients. No confidence interval for FMD is reported in the registry record.
How should a p-value be understood?
In general, a p-value is calculated in relation to a null hypothesis and a statistical model. It describes how unusual the data, or data more extreme, would be under that hypothesis and model. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. A p-value is more informative when read alongside an estimated contrast and its confidence interval. The registry record does not report a primary-outcome p-value or identify the test used.
What does randomization contribute?
In general, random assignment is intended to make treatment groups comparable, on average, with respect to factors known and unknown at assignment. That design supports a treatment comparison, but it does not guarantee balance in a particular study or remove problems arising after assignment, such as missing outcomes or departures from the intended analysis. The registry record identifies the study as randomized but does not describe the randomization sequence, allocation concealment, or the analysis population.
What is the role of masking?
In general, masking can reduce the influence of knowledge of assignment on participant experience, clinical care, measurement, or interpretation. Its effectiveness depends on who was masked and whether treatment assignment could be inferred. The record describes the study as double-masked but does not identify the masked parties or detail how masking was maintained or assessed.
What do planning calculations mean?
In general, a sample-size calculation uses assumptions about the outcome, variability, allocation, significance level, and target power to illustrate the amount of information a future study may need for a specified effect. The registry record describes planning illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect and that non-time-to-event illustrations are expressed as participants per arm.
These calculations are planning illustrations, not evidence about the probability that this completed study detected an effect. They are not observed power. The numerical planning results and the observed FMD effect are not reported in the registry record. The sample-size justification used to design the study is also not reported in the registry record, so the planning illustrations should not be assumed to represent the original design calculation.
Why can over-dispersion matter?
In general, over-dispersion means that observed variability is greater than a statistical model expects. When a model assumes less variability than the data contain, standard errors may be too small and uncertainty may be understated. This concept is especially relevant to outcomes whose variability is modeled directly, but the registry record does not report a model for the FMD outcome or evidence of over-dispersion. It would therefore be inappropriate to claim that over-dispersion affected this study’s analysis.
Overall, the record specifies the endpoint and some design features but does not provide enough analysis detail to reproduce or fully assess the primary comparison. The statistical model, treatment-effect estimate, uncertainty interval, test, and assumptions actually used are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists FMD as the primary outcome and lists secondary outcomes covering the 6MWT, KCCQ12, VAS, serum IL-18, and serum IL-6. It identifies six outcome measures in total, but it does not report results or a statistical plan for controlling the chance of false-positive findings across multiple outcomes or analyses. Whether any multiplicity adjustment was used is not reported in the registry record.
Multiplicity is a general concern when several outcomes, time points, subgroups, or statistical comparisons are examined. Each additional analysis can create another opportunity for a result to appear unusual by chance. Approaches to address this can include prespecifying a primary comparison, adjusting significance thresholds, or treating secondary findings as exploratory. Which approach, if any, was used in this study is not reported in the registry record. The record’s stated aim to identify participants who might be more likely to benefit raises questions about subgroup assessment, but the analysis plan and results for that aim are not reported.
Missing-data methods and analysis populations are also not reported in the registry record. The record does not describe withdrawals, incomplete FMD measurements, reasons for missingness, imputation, or whether participants were analyzed according to randomized assignment. These details matter because an analysis based only on participants with observed measurements may differ from an analysis that accounts for missing outcomes, particularly if missingness is related to participants’ health or treatment experience.
The registry record lists the study as completed, but completion status does not establish that each outcome was available for every randomized participant. Without endpoint-specific denominators and missing-data procedures, the completeness of the primary outcome and the populations contributing to secondary analyses cannot be assessed. The number of analyses recorded is zero, so no analysis results are listed in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Vericiguat | 3 | 13 | 23.1% |
| Placebo | 1 | 12 | 8.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Vericiguat | 0 of 13 |
| Placebo | 0 of 12 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Vericiguat | 5 of 13 |
| Placebo | 6 of 12 |
Most frequent serious adverse event terms
| Event term | Organ system | Vericiguat | Placebo |
|---|---|---|---|
| Hospitalization | Cardiac disorders | 3 of 13 | 1 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Vericiguat | Placebo |
|---|---|---|---|
| Dizziness | General disorders | 5 of 13 | 6 of 12 |
| Fatigue | General disorders | 3 of 13 | 3 of 12 |
| Hypotension | Vascular disorders | 1 of 13 | 1 of 12 |
| Headache | General disorders | 0 of 13 | 1 of 12 |
| New onset anemia | Blood and lymphatic system disorders | 1 of 13 | 0 of 12 |
Serious events with the highest arm-level rate: hospitalization (23.1%).
The registry record reports serious adverse events and other adverse events separately for vericiguat and placebo. For serious adverse events, it lists 3 affected participants among 13 at risk in the vericiguat group and 1 affected participant among 12 at risk in the placebo group. For other adverse events, it lists 5 affected participants among 13 at risk in the vericiguat group and 6 affected participants among 12 at risk in the placebo group. Deaths are listed as 0 in each group.
The registry also identifies hospitalization as a top serious-event term, with 23.1% reported. The record does not specify the denominator or further context for that percentage in the information available, so it should be read as a registry-listed percentage rather than as a basis for a new calculation.
These figures are descriptive safety counts, not proof that an event was caused by the assigned treatment. The record does not provide event-level narratives, severity grades, timing, statistical comparisons, or details about how relatedness was assessed. It also does not explain whether the categories can overlap for an individual participant. The counts should therefore be read as reported, without combining categories or inferring comparative risk from them. A complete safety assessment would require more detail than is reported in the registry record.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, double-masked, parallel phase 4 study compared vericiguat with placebo in people with HFrEF, with FMD change from baseline to 12 weeks designated as the primary endpoint. It also documents a completed study and lists other outcomes addressing exercise capacity, health status, a visual analogue measure, and inflammatory biomarkers. These details identify the scientific question and the kinds of outcomes the study intended to examine.
The record does not report primary or secondary outcome estimates. It therefore does not show whether FMD changed in either group, whether the groups differed, how large any difference was, or how precisely a difference was estimated. There is no basis in the registry record for claiming that vericiguat improved or worsened vascular function, health status, exercise capacity, or inflammatory markers. The absence of posted analyses is not evidence that there was no effect; it means the registered record does not allow the effect to be evaluated.
The study’s stated interest in identifying participants who may be more likely to benefit is an aim, not a demonstrated finding. The record does not report a subgroup definition, predictive model, or test of whether treatment effects varied by baseline vascular function or inflammatory status. Any such interpretation would go beyond the available results.
The adverse-event counts describe events recorded by treatment group, but they do not establish causation or provide a complete account of the safety profile. Their interpretation is constrained by the lack of event details and comparative analyses in the registry record.
In general, a clinical trial result is most interpretable when an effect estimate is accompanied by an uncertainty interval, a clear account of the analysis population, and sufficient outcome and safety detail. Those elements are not reported for the primary comparison in this record. The appropriate conclusion is therefore limited: the study was registered with a defined primary physiological endpoint and completed, but its posted results do not permit a quantitative judgment about the treatment comparison.
13. Why This Trial Matters Statistically
This trial is statistically notable for asking a mechanistic question through a continuous physiological endpoint. FMD quantifies a change in brachial artery diameter following cuff release and is recorded as a percentage increase from the pre-occlusion value. The endpoint is distinct from the study’s patient-reported, exercise, and biomarker outcomes. Keeping these outcome types separate helps avoid treating a change in a physiological measure as interchangeable with a change in symptoms or daily health status.
The randomized, double-masked, parallel design is relevant to how a treatment comparison could be interpreted. In general, randomization aims to reduce systematic differences between groups at assignment, while masking may limit expectation-related influences on measurement or care. However, the registry record does not report the operational details needed to assess those procedures, nor the analysis used to estimate the primary contrast.
The study description also raises a statistical question about whether baseline vascular dysfunction and inflammation identify participants with different treatment responses. Such a claim requires more than observing a response within a selected subgroup. In general, it requires a suitable analysis of whether the treatment effect differs across levels of a baseline characteristic, with attention to multiplicity and uncertainty. The registry record does not report such an analysis or its findings.
The posted results do not include the primary endpoint estimate, confidence interval, or analysis. This makes the record useful for understanding the intended question and design, but not for evaluating the size or precision of a treatment effect. That distinction matters: registration details describe what was planned or intended, whereas outcome estimates are needed to assess what the study observed.
14. 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 most important limitation for interpreting this trial from the registry record is the absence of primary outcome results. FMD is defined and its timeframe is stated, but group results, a treatment contrast, and uncertainty estimates are not reported. The record also lists no analysis results. Consequently, the intended primary comparison cannot be evaluated quantitatively.
Details needed to assess the conduct and analysis are not reported in the registry record. These include participant characteristics, endpoint-specific numbers analyzed, missing-data procedures, analysis populations, the statistical model, and the handling of multiple outcomes. Randomization and double masking are identified, but the procedures for allocation and masking are not described. The study’s sample-size justification is not reported in the registry record.
The brief summary describes an interest in identifying participants based on baseline vascular function and inflammatory status, but the record does not report the definition of those features, a prespecified subgroup analysis, or results. Without those details, the predictive aim cannot be assessed. The secondary outcomes are listed, but their estimates and analysis methods are not reported.
The safety information is limited to group-level counts, at-risk counts, deaths, and a listed serious-event term. Event timing, participant-level detail, attribution, severity, and comparative statistical analyses are not reported in the registry record. These limitations prevent a detailed assessment of either efficacy or safety from the posted results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: The Effect of Vericiguat on Peripheral Vascular Function, Patient Health Status and Inflammation — NCT05420012.
- Registry record last updated 2025-10-08; status last verified 2025-09.
- Results first posted 2025-10-08.
- 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.
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18. Record Summary
This completed phase 4 study is registered as a randomized, double-masked, parallel comparison of vericiguat and placebo in people with HFrEF. The registry lists an enrollment of 26 and identifies FMD change from baseline to 12 weeks as the primary endpoint. FMD is defined as the maximal change in brachial artery diameter following cuff release, expressed as a percentage increase from the pre-occlusion value.
Listed secondary outcomes include the 6MWT, KCCQ12, VAS, serum IL-18, and serum IL-6. The study description also states an aim to identify participants who may be more likely to benefit based on baseline vascular function and inflammation. The registry record does not report primary or secondary outcome results, analysis methods, missing-data procedures, or findings for the predictive aim.
Serious and other adverse-event counts are listed for both groups, with 0 deaths in each. These counts are descriptive and do not establish causation. The record’s design information clarifies what the study intended to compare; the absence of outcome analyses means its treatment effect and precision cannot be determined from the posted results.