Sex Differences in the Dilatory Response of Compound 21: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sex Differences in the Dilatory Response of Compound 21 (NCT05576155), a non-randomized early/phase 1 study. The primary outcome is Microvascular AT2R Sensitivity Following Local Control Treatment.

2. Clinical Question

3. Trial Design

The registry identifies NCT05576155 as an early-phase 1, non-randomized, unmasked, parallel study. Its status is completed. The recorded start date is 2022-10-03, and the primary completion date is 2023-02-23. Enrollment is listed as 26. These registry entries describe the planned and recorded study structure; they do not establish how many participants contributed data to the primary outcome.

The study title is “Sex Differences in the Dilatory Response of Compound 21.” The primary outcome description says that investigators measured a cutaneous vascular dilator response to exogenous Compound 21 perfusion in young men and women. The stated measurement approach combines laser-Doppler flowmetry with intradermal microdialysis delivery of Compound 21. The record also lists local losartan perfusion and local lactated Ringer's control perfusion, each described as lasting approximately one hour through an intradermal microdialysis fiber.

The record lists Compound 21 and Compound 21 + losartan as interventions. It separately gives descriptions for local losartan perfusion and local lactated Ringer's control perfusion. It does not fully explain the relationship between these intervention names, perfusion descriptions, and analysis groups. The allocation is explicitly non-randomized, so treatment assignment should not be interpreted as randomized. The registry also states that the arms are not a like-for-like control comparison. Consequently, any comparison between groups could reflect differences beyond the treatment conditions, and the design does not support the same interpretation as a randomized controlled comparison.

Circulating progesterone and testosterone, and circulating estradiol, are listed as secondary outcomes. The registry record does not report their outcome values, the methods used to analyze them, or further details of participant eligibility and allocation.

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

Reasons for not completing this period:

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 Microvascular AT2R Sensitivity Following Local Control Treatment, measured over post 1 hour of local control treatment.

The primary endpoint is titled “Microvascular AT2R Sensitivity Following Local Control Treatment.” It is defined as the cutaneous vascular vasodilator response to exogenous Compound 21 perfusion, measured as a mean expressed in percentage of maximal blood flow. The stated timeframe is after one hour of local control treatment. The measurement uses laser-Doppler flowmetry together with intradermal microdialysis delivery of Compound 21.

In general, a continuous endpoint records a measurement along a scale rather than sorting each participant into a simple category. A mean describes the average recorded value for a group. The registry specifies standard error as the dispersion measure. In general, standard error describes the precision of an estimated mean, rather than the spread of individual participant measurements. It should not be read as a range containing most individual observations.

The endpoint is used to quantify a local vascular response under the specified measurement conditions. The registry’s rationale describes angiotensin II receptors as having opposing roles in vessel constriction and dilation, and presents Compound 21 perfusion as a way to examine AT2R sensitivity. The stated outcome is a physiological measurement in skin microvessels; it is not itself a measure of cardiovascular disease or a clinical event. The registry record does not report the group means, standard errors, participant-level distributions, or a treatment or sex comparison for this endpoint. Therefore, the magnitude and precision of the observed response are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary outcome as a mean of a continuous measure, with standard error as its dispersion measure. It does not report the specific statistical model or test used to analyze that endpoint. The explanations below describe general statistical concepts; they should not be mistaken for methods confirmed to have been used in this study.

What does a mean describe?

In general, a mean is an average that condenses a set of measurements into a single summary. For a continuous physiological outcome, it can describe the typical measured level within a group. A mean alone does not show whether participants had similar responses or whether a few values were far from the rest. Individual-level distributions, medians, and other summaries can help characterize that pattern, but such results are not reported in the registry record.

The primary outcome is expressed as a percentage of maximal blood flow. This scale gives the response a reference point tied to maximal flow, as described in the endpoint definition. The registry does not provide the observed values, details of how maximal blood flow was established, or information about the distribution of measurements. No further measurement or transformation details are reported in the registry record.

What does standard error mean?

In general, standard error describes uncertainty in an estimated summary, such as a mean. It is not the same as the standard deviation, which describes variability among individual observations. A small standard error indicates that the estimated mean is relatively precise under the assumptions of the analysis; it does not imply that individual responses are tightly clustered. The registry names standard error but reports no numerical value for it, so the precision of the primary mean cannot be assessed.

In general, a confidence interval combines an estimate with a range of values compatible with the data and the interval procedure. Its width reflects precision, and its endpoints help show which effect sizes remain plausible under the stated method. No confidence interval for the primary endpoint or a group contrast is reported in the registry record. A p-value, if available, would address compatibility with a specified null model under assumptions; it would not by itself give the size or practical importance of a difference. No primary-outcome p-value is reported.

What would a group comparison require?

In general, comparing group means requires a clearly defined contrast, an estimate of that contrast, and a method for quantifying uncertainty. The comparison also depends on the study design and the assumptions of the analysis. The registry describes a non-randomized parallel study and explicitly cautions that the arms are not a like-for-like control comparison. Non-random allocation can leave group differences associated with factors other than the condition being examined. Statistical adjustment can sometimes address measured differences, but it cannot automatically remove unmeasured confounding. The registry record does not report whether any adjustment was performed.

The title focuses on sex differences, but the record does not identify a statistical model for that question. It does not report whether the investigators compared group means directly, adjusted for other variables, or tested a treatment-by-sex interaction. Those approaches answer distinct questions and require their own estimates and uncertainty. Their use in this study is not reported in the registry record.

What do the planning assumptions mean?

The registry describes a sample-size planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration is described as detecting a stated fraction of the observed effect. These are planning assumptions, not reported features of the trial's own design justification. The record does not report the trial's sample-size justification or whether the study was designed around these assumptions.

In general, a sample-size calculation estimates how many participants would be needed under specified assumptions to detect an effect of a chosen size with a chosen probability, while controlling a specified error rate. Such a calculation depends on the target effect, variability, design, and analysis method. A planning illustration based on an observed effect is conditional on that effect and its assumptions. It does not show the probability that this completed study detected an effect and must not be interpreted as observed power. The illustration’s arm allocation assumptions also should not be mistaken for evidence that the actual study randomized participants equally between arms.

The record identifies a continuous outcome, but does not provide the actual sample-size illustration values in the registry record recorded for this analysis. It also does not report a protocol-based sample-size rationale, assumptions about outcome variability, or a planned target effect. No independent calculation is warranted from the information recorded.

What is not known about the analysis?

The record reports zero analyses. It does not report a statistical analysis plan, the exact tests or models, assumptions checks, handling of repeated or correlated measurements, covariates, or the intended treatment of outliers. It does not report interim analyses. None of these methods should be inferred from the endpoint description or from the existence of planning assumptions. The registry record also does not report confidence intervals, test statistics, effect estimates, or numerical outcome summaries for the primary endpoint.

Because the primary endpoint is a physiological measurement obtained through a specified local procedure, analysis choices could affect how the measurements are summarized and compared. In general, methods should reflect the outcome scale, study design, and dependencies among observations. But whether there were repeated measurements, how they were handled, and whether the method accounted for any dependencies are not reported in the registry record. The listed mean and standard error identify the intended form of summary, not the full analysis method.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Young Men", "Young Women")
n   <- c(12, 12)
m   <- c(15, 25)
sp  <- c(2, 4)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Young Men  12  15.000  6.928  10.598  19.402
CARM  Young Women  12  25.000  13.856  16.196  33.804

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures and identifies circulating progesterone and testosterone, and circulating estradiol, as secondary outcomes. It does not give the full outcome definitions or numerical results for those secondary measures in the record. It also reports zero analyses. The statistical analysis plan, if any, is not reported in the registry record.

In general, multiplicity arises when several outcomes, comparisons, subgroups, or time points are tested. Looking across many tests can increase the chance of at least one apparently notable result even when there is no underlying effect. Statistical plans may address this by identifying a primary question in advance or by adjusting inference across tests. The registry record does not report whether any multiplicity strategy was planned or used. It is therefore not possible to determine how the listed outcomes were prioritized or how any multiple comparisons would have been interpreted.

The record describes a primary outcome after local control treatment and lists secondary hormone outcomes, but does not report a hierarchy or analysis population for each measure. It does not report whether subgroup analyses were prespecified. Any claim about selective reporting or adjustment would go beyond what is recorded.

Missing-data counts, reasons for missing measurements, and methods for handling missing data are not reported in the registry record. The record also does not specify an intention-to-treat, per-protocol, or other analysis population. Enrollment and the safety entries do not establish how many participants had primary outcome measurements available. In general, missingness can affect both precision and interpretation, particularly if the availability of measurements is related to participant characteristics or observed response. Without outcome-specific denominators and missing-data methods, the extent and possible influence of missing observations cannot be assessed.

12. 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 0% reporting threshold.

The registry safety entries display two groups: Young Men and Young Women. For each displayed group, the number at risk is 12 for serious adverse events and 12 for other adverse events. The number affected is recorded as 0 for serious adverse events and 0 for other adverse events. Deaths are recorded as 0 in each group. These are the adverse-event figures reported in the registry record.

In general, a count of zero reported events means that the record lists no events in that category among the participants represented by the entry. It does not establish that an event is impossible, nor does it show how precisely a rare risk has been estimated. Safety counts are descriptive and should be read with their denominators and reporting definitions. The registry does not provide further event details, follow-up duration, or a narrative of safety monitoring in the registry record recorded for this analysis.

The displayed safety denominators should not be assumed to be the number included in the primary endpoint analysis. The registry record does not report the outcome-specific analysis population or explain the relationship between enrollment and these safety entries. These figures describe reported adverse events; they do not supply evidence about the vascular-response outcome.

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

The record describes a study designed to examine a cutaneous vascular response to Compound 21 in young men and women. It specifies a mean outcome measured as a percentage of maximal blood flow, with standard error as the dispersion measure. It also explains a biological rationale involving angiotensin II receptor pathways and the possible relevance of estrogen. These details establish the topic and the intended measurement, but they do not reveal the observed response.

The primary outcome values and the comparison between men and women are not reported in the registry record. The record therefore cannot establish whether the observed response differed between groups, how large any difference was, or how precisely it was estimated. The absence of reported results is not evidence of no difference. Nor does the trial title, completed status, or listed outcome definition establish a particular result.

The measurement is local and physiological: the registry describes blood flow in skin microvessels during Compound 21 perfusion after local control treatment. In general, results from such a measurement address the response under those study conditions. They do not, by themselves, establish effects on blood pressure, cardiovascular disease, or clinical outcomes. The registry record does not report such clinical outcomes.

The non-randomized allocation is an important qualification. The registry explicitly states that the arms are not a like-for-like control comparison. In general, non-randomized group differences may reflect both the conditions under study and other differences between groups. The record does not report an adjusted analysis that could clarify this issue. Any interpretation of a group contrast would need to account for the design and the specific analysis, neither of which is reported in sufficient detail.

The secondary hormone outcomes are listed, but their results and analyses are not reported. The safety entries report zero serious and zero other adverse events among the listed at-risk groups, with zero deaths. Those entries should be understood as registry-reported counts, not as proof that no risk exists or as an explanation of the primary physiological response.

14. Why This Trial Matters Statistically

This study is statistically notable because its title poses a group-difference question while the record identifies a non-randomized design. That distinction matters: a comparison of observed groups is not automatically a causal estimate of the effect of a treatment or biological characteristic. In general, random allocation helps balance both measured and unmeasured characteristics on average; non-random allocation does not provide that design-based protection. The registry itself cautions that the arms are not a like-for-like control comparison.

The primary outcome is a continuous physiological measure, summarized as a mean with standard error. This pairing illustrates why an estimate and a measure of precision should be considered together. A mean describes the group-level response, while the standard error describes uncertainty in that mean. Neither is reported numerically in the record, so readers cannot judge the effect size or its precision. The lack of a reported comparison also means that the title cannot be treated as a statistical finding.

The endpoint is tied to a particular local measurement setting: Compound 21 is delivered through intradermal microdialysis, and blood flow is measured by laser-Doppler flowmetry. The study therefore asks a specific physiological question rather than a broad question about clinical outcomes. This focus can be useful for studying vascular mechanisms, but it also defines the scope of what the recorded endpoint can support.

Finally, the registry illustrates the difference between study status and result transparency. The study is marked completed, yet the primary outcome estimates, uncertainty, and analysis are not reported in the registry record. Without those elements, readers cannot evaluate the magnitude, precision, or robustness of the stated question's answer. The record's design and endpoint remain informative, but they are not substitutes for outcome results.

15. 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 main limitation for statistical interpretation is that the registry record does not report the primary outcome results. It gives the outcome definition and summary format, but not the means, standard errors, group contrast, confidence interval, test statistic, or p-value. The magnitude and precision of the response therefore cannot be assessed from the recorded information.

The non-randomized allocation and the explicit warning that arms are not a like-for-like control comparison limit interpretation of any group differences. The record does not report participant characteristics by group, a statistical adjustment strategy, or an analysis explaining how potential group differences were handled. The intervention and arm descriptions are also not fully mapped to one another in the registry record recorded for this analysis.

The primary endpoint is a local cutaneous vascular response. It should not be generalized automatically to other vascular beds or clinical outcomes. The registry describes healthy young participants, but its fuller population description is not reported in the registry record. Eligibility criteria and detailed participant characteristics are also not reported.

Outcome-specific denominators, missing-data counts, and missing-data methods are not reported. The safety entries do not determine the primary analysis population. The registry lists secondary hormone measures but does not report their results or analyses. It also does not report the statistical analysis plan, multiplicity approach, interim analyses, or sample-size justification. These gaps preclude assessment of the planned analytic choices and the completeness of the reported outcome evidence.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sex Differences in the Dilatory Response of Compound 21 — NCT05576155.
• Registry record last updated 2024-12-31; status last verified 2024-12.
• Results first posted 2024-12-31.
• 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.

19. Record Summary

NCT05576155 is titled “Sex Differences in the Dilatory Response of Compound 21.” The registry lists it as an early-phase 1, non-randomized, unmasked, parallel study and marks its status as completed. The recorded start date is 2022-10-03, the primary completion date is 2023-02-23, and enrollment is 26. Anna Stanhewicz, PhD, is listed as sponsor.

The primary outcome concerns mean cutaneous vasodilator response to Compound 21, expressed as a percentage of maximal blood flow after local control treatment, with standard error specified as the dispersion measure. The described measurement combines laser-Doppler flowmetry and intradermal microdialysis. Secondary outcomes include circulating progesterone and testosterone, and circulating estradiol.

The registry record does not report primary or secondary outcome results, numerical uncertainty estimates, or the statistical analyses. Its non-randomized design is accompanied by a warning that the arms are not a like-for-like control comparison. Safety entries report zero serious adverse events, zero other adverse events, and zero deaths in each displayed group.