Peripheral Vascular Effects of Sulfhydryl-containing Antihypertensive Pharmacotherapy on Microvessels in Humans: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Peripheral Vascular Effects of Sulfhydryl-containing Antihypertensive Pharmacotherapy on Microvessels in Humans (NCT03179163), a randomized phase 1, phase 2 study. The primary outcome is Change in Endothelium Dependent Vasodilation.

2. Clinical Question

The question is mechanistic and physiological: it concerns a measured response in small vessels, rather than a clinical event or a long-term health outcome. The study summary describes localized forearm experiments, including microdialysis procedures in which research substances are perfused into the skin. Those experimental procedures are intended to assess vascular responses; the primary endpoint is the reported change in an area-under-the-curve measure.

Random allocation is described for the three hypertensive treatment groups. The registry record does not state the allocation ratio or report how many participants were assigned to each group. It also does not give the primary result by group, so the comparison of the drugs cannot be assessed from the reported endpoint information alone.

3. Trial Design

The registry describes a randomized, double-masked, parallel study in phase I and phase II. The listed enrollment is 10. The study is marked terminated. Its recorded start date is 2016-07-20, and its primary completion date is 2022-08-31. These registry entries describe the study record; they do not establish how many participants completed treatment or contributed data to the primary endpoint.

The hypertensive treatment arms are captopril, enalapril, and hydrochlorothiazide. Captopril is described as an ACE inhibitor with a sulfhydryl donor, enalapril as an ACE inhibitor, and hydrochlorothiazide as a diuretic. The study summary says participants with hypertension were randomly assigned one of the three drugs, took it for 16 weeks, and repeated the experiments. The record also describes a normotensive group that performed the experiments without taking study drugs. It does not report how the normotensive participants were selected or whether they were matched to the hypertensive participants.

A parallel design assigns participants to a treatment group rather than having each participant receive every treatment in sequence. Randomization is intended to reduce systematic differences between treatment groups, while masking is intended to limit the influence of treatment knowledge on study conduct or assessment. These are general purposes of the design features; the registry record does not describe the randomization procedure, who was masked, or whether masking was maintained.

The study title and summary focus on microvascular function and vessel remodeling in people with hypertension. The primary endpoint is a change in endothelium-dependent vasodilation over 16 weeks. Systolic and diastolic blood pressure are listed as secondary outcomes. The registry record does not report a detailed schedule of measurements or the analysis population for any outcome.

The status is terminated, but the reason for termination is not reported in the registry record. The planned enrollment and status should therefore not be treated as evidence of actual enrollment, treatment completion, or analysis completion. The registry record does not report why the study ended, whether the planned enrollment was reached, or whether any protocol changes occurred.

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 Change in Endothelium Dependent Vasodilation, measured over 16 weeks.

The primary endpoint is titled “Change in Endothelium Dependent Vasodilation.” It is described as a laser Doppler measurement of blood flow during localized perfusion of acetylcholine, an endothelium-dependent vasodilator. The instrument produces a qualitative, dimensionless index of blood flow. The endpoint is expressed as differences in area-under-the-curve units: (laser Doppler flux/MAP)*logAch concentration. MAP refers to mean arterial pressure in the unit description.

In general, an area-under-the-curve measure can combine a response across a range of administered concentrations into one summary value. In this study, the response is measured during an acetylcholine dose-response procedure. Endothelium-dependent vasodilation is used as a physiological measure because it reflects the ability of vessels to respond through endothelial pathways. This makes it relevant to a study focused on microvascular function and possible remodeling associated with hypertension and its treatment.

The registry gives the timeframe as 16 weeks and describes experiments before and after treatment in the study summary. However, the record does not report the numerical baseline and follow-up values, the calculated change for each group, or the exact convention used to subtract measurements. It also does not report the primary endpoint results or a comparison among the treatment groups. The measure’s definition and rationale can therefore be described, but the magnitude and precision of any observed response cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a continuous measure analyzed as a mean, with standard deviation as its dispersion measure. In general, a mean expresses the average value in a group, and a standard deviation describes how spread out the participant measurements are around that average. These summaries are useful for describing a continuous endpoint, but their interpretation depends on the number of observations and the distribution of the measurements. The registry record does not report primary-outcome means, standard deviations, or the number of observations contributing to them.

The endpoint is a change in an area-under-the-curve measure of endothelium-dependent vasodilation over 16 weeks. For a change score, an analysis can compare within-participant measurements over time, compare changes between groups, or use a model that accounts for baseline values. These are general analytical options, not a description of the analysis used in this study. The registry record does not report how change was calculated, whether baseline values were included as covariates, or what statistical model was used.

Randomization is a design method intended to make treatment groups comparable with respect to factors known and unknown at the time of assignment. A parallel-group structure keeps each participant in an assigned treatment group rather than switching treatments. Double masking is intended to limit the influence of treatment awareness. These design labels do not, by themselves, establish that groups were balanced or that masking was successful. The randomization method, allocation ratio, masking details, and any assessment of baseline balance are not reported in the registry record.

The record includes a planning description for sample-size illustrations: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. Such illustrations are prospective planning calculations, not observed power. They are conditional on assumptions about the effect and variability and should not be read as evidence about the precision of the actual study. The registry record does not report the trial’s own sample-size justification or enough primary-outcome summary data to interpret a recalculated two-arm effect. The record indicates that fewer than two arms have primary-outcome data for the analysis.

In general, a two-sided test considers departures in either direction from a null value. A significance level is a threshold selected for a testing procedure; it is not the probability that the null hypothesis is true. A normal approximation uses properties of the normal distribution to estimate uncertainty or conduct a test. Whether that approximation is suitable depends on the data and design. The registry record does not identify the test used for the primary outcome or state whether assumptions were checked.

Confidence intervals are a general way to express uncertainty around an estimated effect. A narrower interval indicates greater precision under the model used, while a wider interval indicates more uncertainty. An interval crossing a null value does not prove that there is no effect, and an interval excluding it does not establish clinical importance. No primary estimate or confidence interval is reported in the registry record, so precision cannot be judged.

For a continuous endpoint, variability may differ across groups, and measurements may depart from assumptions used by a simple normal model. General methods can account for unequal variability or other distributional features, but choosing among them requires information about the outcome data and the planned analysis. The registry record does not report diagnostic checks, transformations, robust methods, or other adjustments. There is no basis for attributing a particular statistical procedure to the investigators beyond the outcome’s mean and standard-deviation designation.

Over-dispersion is a general issue most commonly discussed for count data: observed variation exceeds what a simpler count model expects. It can make standard errors too small if ignored. The primary endpoint in this record is continuous, not a reported count outcome, so over-dispersion is not a documented feature of this analysis. More generally, the registry record does not report model diagnostics or whether any departures from assumptions were addressed.

Planning illustrations based on a fraction of an observed effect are not actual trial results and do not establish the chance that this completed study detected an effect. They are not observed power. The record has no posted primary effect estimate from which the planning assumptions can be interpreted, and its analysis status indicates that a two-arm primary comparison is unavailable. No recalculated estimate or sample-size value should therefore be treated as a result of the trial.

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("Hypertensive - ACEi +SH")
n   <- c(10)
m   <- c(83)
sp  <- c(47)
sd  <- sp      # posted standard deviations
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  Hypertensive - ACEi +SH  10  83.000  47.000  49.378  116.622

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome, change in endothelium-dependent vasodilation, and two secondary outcomes: systolic blood pressure and diastolic blood pressure. It does not report a multiplicity strategy, such as a hierarchy of hypotheses, an adjustment to testing thresholds, or a plan for interpreting several comparisons. The number of outcomes alone does not establish how many statistical tests were performed. The analysis plan for multiple outcomes and treatment contrasts is not reported in the registry record.

Missing data can affect estimates when participants do not have measurements at all planned time points. In general, an analysis may rely on assumptions about why observations are missing, and different assumptions can lead to different estimates. The registry record does not report missing primary-outcome measurements, reasons for missingness, imputation methods, or sensitivity analyses. It is therefore not possible to assess whether missing data influenced the reported results.

The record does not specify the analysis population. It does not say whether analyses were based on randomized assignment, treatment received, participants who completed the study, or another group. These definitions can matter when participants discontinue treatment or have incomplete measurements. The listed enrollment of 10 is not a substitute for a reported analysis denominator, and the number contributing to each outcome is not reported in the registry record.

The study status is terminated, but the reason for termination and its consequences for outcome collection are not reported. The registry identifies fewer than two arms with primary-outcome information for analysis, so a treatment comparison cannot be reconstructed from the posted record. Multiplicity, missingness, and analysis-population decisions remain unresolved in the registry information.

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 adverse-event record lists the hypertensive ACEi +SH group. For that group, 10 participants are recorded as at risk of serious adverse events and 0 as affected; the corresponding figures for other adverse events are 10 at risk and 0 affected. Deaths are listed as 0. No serious adverse-event terms are listed.

These are registry counts, not a complete description of all possible safety outcomes. A count of 0 affected means that no affected participants are recorded in the listed group for the listed event category; it does not prove that the treatment has no risk. The record does not provide event narratives, severity details for other events, follow-up completeness, or a comparison of safety outcomes across all treatment arms.

Only one group is listed in the adverse-event data. The absence of listed figures for the other arms does not establish that their event counts were also 0. The registry record does not report a comparative safety analysis or explain the scope of adverse-event collection. These counts should therefore be interpreted as limited recorded observations, not as evidence that the treatments have equivalent safety profiles.

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

The record establishes that this was a randomized, double-masked, parallel study of antihypertensive treatment and microvascular function. It identifies the treatment groups, the normotensive experimental group, the primary physiological endpoint, and a 16-week timeframe. It also records that the study was terminated and lists enrollment as 10. These details describe the registered study, but they do not provide the primary outcome result.

The primary outcome is a laser Doppler measure of endothelium-dependent vasodilation during acetylcholine perfusion. It is relevant to the study’s mechanistic question about microvascular function and remodeling. However, the registry record does not report the observed changes, group summaries, treatment contrasts, confidence intervals, or p-values. The direction and magnitude of the endpoint response are therefore unknown from the record.

That absence should not be interpreted as evidence that the interventions had no effect. It also does not support a claim that the drugs were equivalent or that one was superior. A statistical conclusion requires an estimate and an assessment of its uncertainty, together with a defined analysis. Those elements are not reported for the primary outcome.

The study’s listed enrollment is not enough to establish how many participants completed treatment or contributed usable endpoint data. The record does not state the analysis population, missing-data approach, or reason for termination. Its indication that fewer than two arms have primary-outcome information prevents a comparison from being reconstructed from the posted results.

Accordingly, the useful interpretation is about the question the study set out to examine, not an answer about treatment effects. The registry describes a physiological investigation of different antihypertensive drug classes, but the primary result and its precision are not reported in the registry record. The listed adverse-event counts are also limited to one group and cannot establish comparative safety.

14. Why This Trial Matters Statistically

This study raises a statistical question that is different from simply asking whether blood pressure changed. It focuses on a physiological endpoint intended to characterize microvascular response, and it compares drugs described as differing in sulfhydryl content and class. That makes the endpoint definition and the treatment contrast central to interpretation.

The design labels—randomized, double-masked, and parallel—are important because they describe ways a trial can reduce bias and support treatment comparisons. But design labels do not substitute for outcome data. To assess the strength of evidence, readers need group estimates, variability, an analysis population, and uncertainty measures. Those primary-outcome details are not reported in the registry record.

The record also illustrates why enrollment and analysis sample size must be distinguished. Enrollment is listed as 10, but the record does not give the number contributing to each outcome or the arm-specific primary results. In a small study, uncertainty can be substantial, but the actual precision cannot be inferred without estimates and their standard errors or confidence intervals. No numerical precision measure for the primary endpoint is reported.

Planning calculations based on an assumed fraction of an observed effect can help frame future study design, but they are not evidence of what the study found. They are not observed power and depend on assumptions that must be interpreted in context. Here, the registry does not report the primary estimate needed to assess such planning assumptions, and it indicates that a two-arm primary analysis is unavailable.

The statistical importance is therefore as much about transparency as about method: a defined endpoint and design can clarify the research question, while absent results leave the effect and its uncertainty undetermined. The registry record cannot support a conclusion about the comparative vascular effects of the treatments.

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 interpretation is that the registry record does not report primary-outcome results. No group-specific mean, standard deviation, change estimate, confidence interval, or p-value is available for endothelium-dependent vasodilation. Without these, neither the magnitude nor the precision of the primary finding can be assessed.

The record lists enrollment as 10 but does not report treatment-arm counts, endpoint-specific denominators, or the number of participants completing the 16-week treatment period. It also does not report the analysis population or missing-data handling. The study is marked terminated, but its reason for termination and any effect on recruitment, follow-up, or analysis are not reported in the registry record.

The endpoint is described as a change in an area-under-the-curve measure, but the record does not provide the calculation convention, analysis model, or detailed measurement schedule. Randomization and double masking are listed, yet their implementation and maintenance are not described. The allocation ratio and baseline characteristics are not reported.

Although blood pressure outcomes are listed as secondary outcomes, their results are not reported. The adverse-event information lists only one group, so it cannot support a comparative assessment across all treatment arms. The record also does not report a multiplicity plan, prespecified analysis details, or sensitivity analyses.

Finally, the registry indicates that fewer than two arms have primary-outcome information for analysis. This prevents reconstruction of a two-arm treatment comparison from the posted record. The available information supports describing the study’s purpose and design, but not estimating its treatment effects.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Peripheral Vascular Effects of Sulfhydryl-containing Antihypertensive Pharmacotherapy on Microvessels in Humans — NCT03179163.
• Registry record last updated 2024-02-28; status last verified 2024-02.
• Results first posted 2024-02-28.
• 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

The registry record describes a randomized, double-masked, parallel phase I/phase II study of antihypertensive pharmacotherapy and microvascular function in humans. Listed enrollment is 10, and the study status is terminated. The record gives a start date of 2016-07-20 and a primary completion date of 2022-08-31.

Hypertensive participants were assigned to captopril, enalapril, or hydrochlorothiazide, with a normotensive group performing experiments without study medication. The primary endpoint is change in endothelium-dependent vasodilation over 16 weeks, measured using laser Doppler flow during acetylcholine perfusion. Systolic and diastolic blood pressure are listed as secondary outcomes.

The primary results, analysis population, missing-data approach, and reason for termination are not reported in the registry record. The registry indicates that fewer than two arms have primary-outcome information for analysis. Adverse-event counts are reported for one group only.