Physiologic Effect of Topical Nitroglycerin on Microcirculation Capacity in Patients With Circulatory Shock.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Physiologic Effect of Topical Nitroglycerin on Microcirculation Capacity in Patients With Circulatory Shock. (NCT05102734), a registered phase not stated study. The primary outcome is Perfused Vessel Density (PVD).

2. Clinical Question

The study asks whether sublingual perfused vessel density (PVD), a measure described as an estimate of functional capillary density, changes after topical nitroglycerin in patients with circulatory shock. It also includes a preoperative control measurement intended to provide a healthy reference for comparison with measurements in patients with shock. The registry record does not report the PVD results, so the direction, size, and precision of any change cannot be assessed.

3. Trial Design

The registry record describes a completed, open-label, single-center study of topical nitroglycerin in circulatory shock. Its brief summary describes participants with shock after cardiac surgery. The recorded enrollment is 44, whereas the brief summary says the study will enroll up to 25 participants with shock. The record does not explain whether the enrollment figure includes the preoperative control group or how these counts relate.

The intervention is listed as a drug, named Nitroglycerin Topical Product. The arm description says a topical nitroglycerin solution was applied to the area of interest. This was not a randomized comparison: allocation is not stated, and the record cautions that the arms are not a like-for-like control comparison. The preoperative control group is described as providing a healthy reference measurement, rather than as a concurrent randomized comparator.

The primary endpoint was PVD, recorded as a mean with standard deviation and reported in mm/mm^2. The preoperative control group had one measurement before surgery. In the topical nitroglycerin group, measurements were obtained after surgery at baseline, then 3-minutes and 30-minutes after topical nitroglycerin administration. The registry record also lists Mean Arterial Pressure, Cardiac Index, and Central Venous Pressure as secondary outcomes.

The recorded study status is COMPLETED. The start date is 2021-09-01, and the primary completion date is 2022-02-01. The record does not report a protocol-level account of the sample-size justification, interim analyses, or detailed analysis plan. The study dates and completion status do not, by themselves, establish that results were posted.

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: 20 patients were enrolled to obtain preoperative control microcirculation measurements only. 20 additional patients would be needed for the NTG challenge. NTG patients were enrolled prior to surgery, but not included if they did not meet postop inclusion criteria.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Sublingual microcirculation measurements were obtained in a preoperative control group to serve as a "healthy" control measurement to compare against measurements in patients with shock. The preoperative control group only had one PVD measurement taken. Sublingual microcirculation measurements in the topical nitroglycerin group were measured after surgery (baseline), then 3-minutes and 30-minutes after NTG solution application.

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 Perfused Vessel Density (PVD), measured over Preoperative Control Group: assessed once preoperatively. For the topical nitroglycerin group, PVD measurements were obtained after surgery (baseline), then 3-minutes and 30-minutes after topical nitroglycerin administration..

The primary endpoint is Perfused Vessel Density (PVD), reported as a mean with standard deviation and a unit of mm/mm^2. The registry description calls PVD an estimate of functional capillary density. In general, a density measure expresses how much of a specified feature is present relative to a defined area; in this context, PVD is intended to characterize perfused vessels in the sublingual microcirculation.

The endpoint is measured at different times for the two groups. The preoperative control group has a single preoperative measurement. In the topical nitroglycerin group, measurements are described at postoperative baseline and at 3-minutes and 30-minutes after administration. These repeated observations can describe the measurement over time in the treated group, while the preoperative value supplies a reference from before surgery.

As a general statistical point, a continuous endpoint preserves the scale and magnitude of the measurement rather than reducing it to a binary category. A mean describes the average measurement in a group or at a time point, while a standard deviation describes variation among observations around that mean. Neither statistic alone establishes a change attributable to an intervention. Interpretation also depends on the observed values, the analysis used to compare measurements, and the uncertainty around any estimated difference. The registry record does not report PVD values, estimates of change, confidence intervals, or tests of statistical significance.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is continuous, and the registry specifies a mean and standard deviation as its summary form. In general, the mean describes the central level of measurements, while the standard deviation indicates how dispersed the individual values are around that mean. The two answer different questions: a similar mean can occur with different degrees of participant-to-participant variability. The registry record does not post either statistic for PVD.

What can a confidence interval tell a reader?

In general, a confidence interval expresses the precision of an estimate under a specified statistical method. A narrow interval indicates greater precision than a wide interval, while both the interval and the estimate need to be interpreted in the context of the study design and measurement. It is not a guarantee that the true value lies within a particular interval, and it does not correct limitations such as nonrandomized group selection or differences in measurement timing. No confidence interval for PVD is reported in the registry record.

Why does the measurement schedule matter?

The topical nitroglycerin group has postoperative baseline and follow-up measurements at 3-minutes and 30-minutes after administration. In general, observations from the same participant over time are related rather than independent. An analysis of change should account for that within-participant relationship if it is estimating a time pattern or comparing time points. Treating repeated observations as if they came from unrelated people can misstate uncertainty. The registry record does not report which method, if any, was used to model repeated measurements.

The preoperative control group has a single measurement before surgery. That reference is not measured at the same phase as the postoperative observations in the topical nitroglycerin group. General comparisons across groups are most straightforward when the groups are comparable in their assignment and assessment conditions. Here, allocation is not stated, the record says the arms are not a like-for-like control comparison, and the control measurement is preoperative. Therefore, even if group values were posted, a difference would not by itself isolate an intervention effect.

What does over-dispersion mean for a continuous outcome?

In general, over-dispersion refers to variability greater than a statistical model assumes. For a continuous measurement, a model that understates the actual variability can produce uncertainty estimates that are too small and results that appear more precise than the data justify. Appropriate modelling depends on the distribution and structure of the observations. The registry record does not describe a model, a distributional assessment, or an over-dispersion check, so no claim about those methods can be made for this study.

How should the planning assumptions be read?

The registry record describes a sample-size planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. The illustration is not the trial's own design justification, and it is a planning exercise rather than observed power. The record does not report the trial's sample-size justification or the resulting planning estimates. Any such illustration should not be read as evidence that the study had a particular probability of detecting an effect.

The planning note distinguishes participants per arm for continuous and other outcomes from total events for time-to-event outcomes. PVD is identified as continuous, but no resulting participant estimate is reported in the registry record. Planning figures depend on assumptions about the target effect, variability, allocation, and analysis. They cannot replace observed outcome estimates or resolve the absence of posted results.

What can be inferred from the listed analyses?

The registry record lists four outcome measures and zero analyses. This indicates that analysis results are not recorded in this entry. It does not establish whether analyses were conducted but not entered, and it does not reveal what statistical tests or models may have been used. The record also does not report a multiplicity adjustment, missing-data method, or analysis population for PVD. Those details are needed to assess how reported estimates were generated and how robust they may be. Without them and without the outcome values, statistical significance, effect size, and precision cannot be evaluated.

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("Preoperative Control Group", "Topical Nitroglycerin Group Postop Baseline", "Topical Nitroglycerin Group 3-minutes Post-NTG", "Topical Nitroglycerin Group 30-minutes Post-NTG")
n   <- c(20, 20, 20, 20)
m   <- c(24.81, 20.44, 26.41, 21.88)
sp  <- c(3.51, 3.38, 3.5, 3.84)
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  Preoperative Control Group  20  24.810  3.510  23.167  26.453
CARM  Topical Nitroglycerin Group Postop Baseline  20  20.440  3.380  18.858  22.022
CARM  Topical Nitroglycerin Group 3-minutes Post-NTG  20  26.410  3.500  24.772  28.048
CARM  Topical Nitroglycerin Group 30-minutes Post-NTG  20  21.880  3.840  20.083  23.677

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists four outcome measures, including PVD as the primary outcome and Mean Arterial Pressure, Cardiac Index, and Central Venous Pressure as secondary outcomes. It records zero analyses. The statistical plan for handling multiple outcomes or multiple time-point comparisons is not reported in the registry record. In general, testing many hypotheses can increase the chance of at least one apparently unusual result, so a prespecified approach to multiplicity can matter. No adjustment or testing hierarchy is described, and no result is posted to assess.

The record does not report how missing PVD measurements were handled, whether all enrolled participants contributed measurements at every time, or how the primary analysis population was defined. It also does not report the number of participants with usable endpoint data. The enrollment figure of 44 and the brief summary's statement of up to 25 participants with shock do not clarify endpoint availability or analysis inclusion.

In general, missing observations can affect interpretation when the likelihood of a missing measurement is related to participant characteristics or outcomes. Statistical methods for incomplete data rely on assumptions, and different assumptions can lead to different estimates. Because the registry record gives no missing-data method or participant flow for the endpoint, the potential effect of missing observations cannot be assessed. No assumptions about the analysis population or missingness mechanism should be inferred from the study's completed status.

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 record lists adverse-event information for Topical Nitroglycerin, Preoperative Control Group, and Post-NTG Challenge. Each listed group has 20 participants at risk for serious adverse events and 0 affected; each also has 20 at risk for other adverse events and 0 affected. Deaths are listed as 0 in each group. No serious adverse-event terms are listed.

These are registry counts, not estimates of comparative risk. The record does not explain the relationship among the three group labels, and the listed counts should not be combined or interpreted as independent groups without further information. The adverse-event entries do not establish the sample size for the primary PVD analysis. The record also does not give event definitions, observation duration, or additional detail about adverse-event ascertainment.

In general, a report of zero observed events means none were recorded in the stated entries; it does not establish that an event is impossible or that the intervention has no safety concerns. The counts should be read in the context of the listed participants and the completeness of reporting. No comparative safety analysis is reported in the registry record.

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

The record documents a study designed to measure sublingual PVD around topical nitroglycerin administration in patients with circulatory shock, alongside a preoperative reference group. It identifies the intended endpoint, its unit, and assessment times. It does not report the observed PVD values or any statistical analysis of them. As a result, it does not establish the direction or magnitude of a measured change, its precision, or whether a statistical test found evidence of a difference.

The design also limits what a group comparison could mean. The preoperative control measurement is taken in a different clinical context from the postoperative measurements, and the registry record cautions that the arms are not a like-for-like control comparison. Allocation is not stated. In general, these features make a direct causal interpretation less secure than a randomized comparison with aligned assessment conditions. The record does not report an adjusted analysis or other method to address differences between groups.

The listed adverse-event counts show zero serious events, other adverse events, and deaths in each of the named entries, with 20 at risk in each entry. These figures describe the registry listings only. They do not provide a comparative safety estimate, and the relationship among the entries is not explained.

Accordingly, the meaningful conclusion from this registry entry is about what was planned and recorded, not about whether PVD changed or what clinical consequences followed. The study is marked completed, but completion does not supply missing outcome estimates. The posted record is insufficient to judge effect size, precision, statistical significance, or the robustness of any analysis. It also cannot support conclusions about benefits or harms beyond the event counts as listed.

14. Why This Trial Matters Statistically

This trial is statistically notable because it combines measurements over time in an intervention group with a reference measurement taken before surgery in a separate control group. In general, repeated measurements can describe how a continuous endpoint varies over time, but the analysis must account for the fact that observations from the same participant are related. A preoperative reference may offer context, yet it does not provide the same comparison as a concurrently assessed randomized control group. The registry record itself cautions that the arms are not a like-for-like comparison.

The outcome is a physiological measurement rather than a patient-centered event, and the registry describes PVD as an estimate of functional capillary density. Such an endpoint can be informative about a measured physiological feature, but interpretation still depends on its observed values, variability, uncertainty, and analysis. None of those PVD results is reported in the registry record. A carefully described measurement schedule is not a substitute for the numerical results needed to assess the endpoint.

The record also illustrates why enrollment and analysis counts need careful reading. It lists enrollment of 44, while the brief summary describes up to 25 participants with shock. The relationship is not explained, and the adverse-event group counts do not establish the number with primary-outcome data. The record lists four outcomes but zero analyses, leaving the result-level statistical interpretation unavailable.

These design and reporting details matter because they define what can be learned from a registry entry. The available information supports a description of the study question and measurement plan. It does not support an estimate of the intervention-associated change in PVD, a claim of statistical significance, or a causal comparison with the preoperative control group.

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.

A central limitation of the registry record is that it does not report the primary outcome values or analyses. No PVD means, standard deviations, estimated changes, confidence intervals, or p-values are available. The study's completed status therefore cannot be used to infer the size, direction, or precision of any observed result.

The comparison structure also requires caution. The study is open-label and single-center, allocation is not stated, and the registry record says the arms are not a like-for-like control comparison. The preoperative control group was measured before surgery, while the topical nitroglycerin group had postoperative measurements. These differences in timing and context limit direct interpretation of any between-group contrast.

There is an unexplained difference between the recorded enrollment of 44 and the brief summary's plan to enroll up to 25 participants with shock. The registry record does not state how these counts relate or how many participants contributed to each PVD assessment. The adverse-event counts cannot be used to fill that gap for the primary endpoint.

The record lists four outcomes and zero analyses, but does not report the statistical methods, multiplicity approach, missing-data handling, or analysis population. It also does not report the sample-size justification or interim analyses. These omissions prevent assessment of the analysis choices, outcome completeness, and precision. The listed safety counts have no accompanying event definitions or observation-duration details in the registry entry.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Physiologic Effect of Topical Nitroglycerin on Microcirculation Capacity in Patients With Circulatory Shock. — NCT05102734.
• Registry record last updated 2024-04-01; status last verified 2024-03.
• Results first posted 2024-04-01.
• 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

NCT05102734 is a completed, open-label, single-center study of topical nitroglycerin and microcirculation measurements in circulatory shock. The recorded enrollment is 44. The brief summary describes up to 25 participants with shock after cardiac surgery, but the relationship between that figure and total enrollment is not explained. The study start date is 2021-09-01, and the primary completion date is 2022-02-01.

The primary endpoint is mean Perfused Vessel Density, in mm/mm^2, with standard deviation. A preoperative control group had one measurement; the topical nitroglycerin group had postoperative baseline and 3-minute and 30-minute post-administration measurements. Secondary outcomes are Mean Arterial Pressure, Cardiac Index, and Central Venous Pressure.

The registry record lists four outcome measures and zero analyses. It does not report PVD results or analysis methods. Adverse-event entries list 20 at risk in each named group, with zero serious events, other events, and deaths. The record cautions that the arms are not a like-for-like control comparison.