Effects of Sublingual and Transdermal Administration of Nitroglycerin for Coronary CT Angiography on Image Quality: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of Sublingual and Transdermal Administration of Nitroglycerin for Coronary CT Angiography on Image Quality (NCT02961946), a randomized phase 4 study. The primary outcome is Coronary Artery Diameter Change.

2. Clinical Question

3. Trial Design

The registry record describes a completed, randomized, single-masked, parallel-group, phase 4 study sponsored by Massachusetts General Hospital. Enrollment is listed as 198. The recorded study start date is 2017-03-15, and the primary completion date is 2017-10-31. The record lists coronary artery disease as the condition and nitroglycerin as the intervention.

Participants were assigned to sublingual nitroglycerin spray, sublingual nitroglycerin tablet, or a nitroglycerin skin patch. The dose descriptions are 0.8 mg for the spray, 0.8 mg for the tablet, and 0.8 mg/h for the patch. The endpoint timeframe states that measurements were obtained on the same day as nitroglycerin administration, during the cCTA exam appointment.

The posted primary outcome results list 66 participants for each arm. Those counts describe the outcome entries; the registry record does not explain whether they reflect all randomized participants, an analysis population, or a particular handling of missing measurements. It also does not report the randomization procedure, the identity of the masked party, adherence, treatment discontinuation, or the detailed conduct of follow-up.

The study description frames the research as an investigation of equivalence in image quality after sublingual or transdermal administration and a feasibility evaluation of transdermal administration. The registry record does not report a protocol-defined equivalence margin, sample-size justification, or statistical plan. Consequently, the design features that are posted establish the broad randomized comparison, but do not provide enough detail to determine how the intended equivalence question was formally tested.

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 Coronary Artery Diameter Change, measured over obtained on the same day (day 0) of nitroglycerine administration (nitroglycerine is administered during the cCTA exam appointment)..

The primary endpoint is the mean change in coronary artery diameter, reported as a fold change. The registry description defines the measure using artery diameters at seven predefined locations across proximal, mid, and distal segments of the left main, left anterior descending, left circumflex, and right coronary artery. Measurements are taken twice at each location. The description says that measurement locations avoid non-calcified and calcified plaque, although proximal or distal deviations from the original locations may be made when plaque is present.

Artery diameter is relevant to the study’s stated imaging question because the trial evaluates image quality after nitroglycerin administration during cCTA. The endpoint summarizes the measured change in diameter rather than reporting an overall image-quality score. The posted arm means are 1.14 for spray, 1.13 for tablet, and 1.15 for patch. Each is accompanied by a 95% confidence interval.

The registry record does not explain the precise calculation underlying the fold change, how measurements from locations and repeated readings were combined, or how any deviations were incorporated. It also does not report a threshold that would distinguish an acceptable from an unacceptable change, nor an equivalence margin. The results therefore describe the reported diameter measure, but do not by themselves establish whether the image quality met a predefined criterion.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean describe?

A mean is an average that condenses measured values into one summary for an arm. Here, the reported measure is coronary artery diameter change in fold-change units. A mean can describe the center of the observed measurements, but does not show their full distribution. Different distributions can have the same mean, and a mean alone does not indicate how much participants’ measurements varied.

The registry record reports the mean for each treatment arm and gives a 95% confidence interval. It does not report a standard deviation, median, range, or participant-level data. Consequently, the posted summaries do not allow a reader to reconstruct the spread of individual measurements or assess whether the mean is affected by unusually high or low observations.

How should a 95% confidence interval be read?

In general, a confidence interval expresses uncertainty in an estimated quantity under the statistical method’s assumptions. It is not a guarantee that a particular proportion of individual measurements falls inside the interval. Nor is it the same as a prediction interval for a new participant. For these results, the intervals are attached to each arm’s mean: 1.12 to 1.15 for spray, 1.09 to 1.16 for tablet, and 1.13 to 1.18 for patch.

The registry record does not state which method produced these intervals or whether it accounted for the repeated readings and artery locations described in the endpoint definition. Without that information, the precision can be described as posted, but the exact assumptions behind the intervals cannot be assessed. The intervals should not be reinterpreted as confidence intervals for treatment differences.

Why are arm summaries not the same as a treatment comparison?

A comparison asks how an outcome differs between arms, not merely what the mean is within each arm. A difference estimate would have its own uncertainty, which depends on the arm estimates and on the analysis approach. The registry record does not post a difference, ratio, contrast confidence interval, or test result. It lists zero analyses. No recalculated two-arm comparison is reported for this continuous endpoint.

Separate confidence intervals may overlap even when a formal contrast test gives a particular result, and their overlap alone does not establish equivalence. Equivalence is a specific statistical claim: the uncertainty around the treatment contrast must be sufficiently contained within a margin defined in advance. The registry record does not report such a margin, nor a formal equivalence analysis. Therefore, the descriptive arm estimates cannot substitute for that test.

What does the endpoint’s fold-change scale mean?

Fold change expresses a measurement on a relative scale rather than as a raw diameter unit. The registry record labels the outcome as fold change and reports means on that scale, but does not explain the exact reference value or calculation used to generate each fold change. It is not appropriate to infer a formula or translate the estimates into a different scale from the information recorded.

The outcome description includes measurements at multiple artery locations and two measurements at each location. It also allows proximal or distal deviations when plaque affects the original location. The record does not explain how location-level values or repeated readings were combined into an arm-level result, how deviations were handled analytically, or whether the statistical model accounted for clustering within participants. These details can matter because measurements from the same participant are generally not independent observations.

What is the role of over-dispersion and repeated measurements?

As a general statistical point, over-dispersion means that variability in data is greater than a model expects. If a model assumes less variability than is present, uncertainty estimates can be too narrow. For repeated measurements, values from one participant or related measurement locations may be correlated; treating correlated observations as independent can also misstate precision. A suitable analysis may need to represent this structure, but the registry record does not describe the model used, so it is not possible to determine how these issues were handled in this study.

The same caution applies to the way measurements are summarized. An average across artery locations may answer a different question from a location-specific analysis. The registry record describes the measurement locations but does not report location-specific results, participant-level distributions, or a method for combining locations. No conclusions about particular artery segments can be drawn from the overall arm means alone.

What can planning calculations tell a reader?

In general, sample-size planning calculations describe how many participants might be needed under specified assumptions to detect a chosen effect with a chosen error rate and power. They are planning illustrations, not observed trial outcomes and not “observed power.” In this record, the stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a fraction of the observed effect. For non-time-to-event outcomes, such illustrations are expressed as participants per arm for a stated power.

Those assumptions do not describe the actual study design unless the registry record says they were used to plan it. The record explicitly does not report its sample-size justification or statistical plan, and no planning result is posted among the outcome details. Accordingly, the posted outcome cannot be used to claim that the trial was adequately powered for equivalence or for a particular treatment contrast.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and does not post secondary outcome results. It reports zero analyses. Although the primary endpoint description involves multiple artery locations and repeated measurements, the record does not explain whether these generated multiple statistical tests, how measurements were combined, or whether any adjustment for multiple comparisons was planned. A multiplicity strategy is not reported in the registry record.

Missing-data handling is also not reported. The outcome entries list 66 participants in each arm, but the record does not say whether all randomized participants contributed measurements, whether any measurements were unavailable, or how missing values were addressed. It does not identify an intention-to-treat, per-protocol, or other analysis population. The listed arm counts therefore should not be assumed to define a particular analysis population.

The record does not describe exclusions, withdrawals, protocol deviations, or sensitivity analyses. These omissions matter because the estimates may depend on who had usable measurements and how incomplete data were handled. No assumptions about missingness or robustness can be assessed from the posted information.

For an equivalence objective, multiplicity and analysis-population choices can affect interpretation, but no protocol or statistical plan is reported. The registry record also does not report an equivalence margin or formal equivalence test. The available summaries therefore support description of the posted arm estimates, while leaving important questions about the planned analysis, missing data, and inferential safeguards unanswered.

11. 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 posts zero serious adverse events for the spray, tablet, and patch groups. It also posts zero participants affected in the other adverse-event category for each group, and zero deaths in each group. These figures are registry summaries for the reporting groups; they are not a treatment-comparison analysis.

A posted count of zero means that the registry record reports no affected participants in that category for the group. It does not, by itself, establish that an event is impossible or that no event could occur outside the recorded observation and reporting process. The record does not describe the adverse-event collection period, definitions, ascertainment procedures, severity criteria beyond the listed serious-event category, or completeness of reporting. It also does not give event-level details or statistical uncertainty for these counts.

Because the record reports zero events in all listed groups, it does not provide a basis for estimating a comparative safety difference from these summaries. The figures should be read as the posted event counts, with the limitations of the registry’s reporting detail in mind, rather than as evidence of a quantified safety advantage for any administration approach.

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

The results describe the mean coronary artery diameter fold change recorded for each nitroglycerin administration group during cCTA. The spray arm mean is 1.14, the tablet arm mean is 1.13, and the patch arm mean is 1.15. The reported 95% confidence intervals give arm-level uncertainty estimates. The posted figures can inform a descriptive understanding of this endpoint under the study conditions recorded.

They do not establish that the approaches are equivalent. Although the study description names equivalence as an aim, the registry record does not report an equivalence margin or an analysis of treatment contrasts. Similar-looking means and overlapping arm confidence intervals are not enough to prove equivalence. Nor do the results establish a difference, because the record provides no formal between-arm estimate or test.

The result is also not a direct measure of every aspect of image quality. It is a diameter-change endpoint constructed from measurements at specified artery locations. The record does not report an overall image-quality score, a threshold for acceptable images, or a link between the diameter measure and diagnostic performance. Conclusions about other imaging outcomes, clinical decisions, or patient outcomes are not supported by these posted results.

The study’s setting and treatment descriptions matter to interpretation: the endpoint was measured on the same day as nitroglycerin administration during the cCTA appointment, and the registry lists the specified spray, tablet, and patch doses. The findings should not be generalized beyond these recorded circumstances without additional evidence. Details on eligibility, participant characteristics, co-interventions, and analysis populations are not reported in the registry record.

In short, the posted data offer three arm-level means and confidence intervals, plus adverse-event counts. They leave the primary comparative and equivalence questions unanswered in the registry results. They also do not reveal the full distribution of measurements, the analysis model, or the treatment contrast’s precision. Reading the summaries as descriptive evidence, rather than as a definitive comparative conclusion, keeps the interpretation aligned with what is reported.

13. Why This Trial Matters Statistically

This trial is statistically notable because its stated aim includes equivalence, while the posted results consist of arm-level means and confidence intervals. Equivalence requires a clear definition of how much difference is acceptable and an analysis of the contrast against that boundary. Neither the margin nor a formal equivalence result is reported in the registry record. This distinction illustrates why similar point estimates do not, by themselves, settle an equivalence question.

The endpoint also illustrates how a concise summary can conceal measurement structure. Coronary artery diameter is measured at multiple predefined locations, with repeated measurements at each location and possible location deviations when plaque is present. The record does not explain how these observations were combined or modeled. In general, accounting for correlations and the structure of repeated measurements is important when estimating precision; without the analysis details, readers cannot evaluate that aspect of the result.

Another statistical lesson is the difference between uncertainty around group means and uncertainty around a treatment contrast. The 95% confidence intervals characterize the posted arm means, but do not directly quantify the difference between approaches. The registry record reports no contrast estimate or analysis. This makes the boundary between descriptive and inferential evidence especially important when interpreting close group summaries.

Finally, the record demonstrates the limits of registry-level reporting for a completed study. It gives the broad randomized design, treatment groups, endpoint definition, and outcome summaries, yet does not report the statistical plan, missing-data methods, analysis populations, sample-size justification, or secondary results. These omissions do not change the posted means, but they constrain what can be inferred about the study’s intended and achieved statistical conclusions.

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 registry record does not report the protocol or detailed statistical analysis plan. It does not specify how randomization was conducted, who was masked, how adherence or treatment discontinuation was handled, or how outcome assessors and measurements were managed. The designation of single masking is recorded, but the masked party is not identified.

For the primary endpoint, the record does not explain the exact fold-change calculation, the approach to combining repeated measurements or artery locations, or the handling of deviations from the predefined measurement sites. It does not report a model, standard deviation, participant-level data, location-specific results, or the method used to calculate the confidence intervals. This limits evaluation of the endpoint’s measurement and uncertainty.

The registry record gives no participant characteristics, eligibility criteria, or analysis-population definition. Although outcome counts are listed by arm, missing-data methods, exclusions, withdrawals, and protocol deviations are not described. The record also does not provide a sample-size justification or enough information to assess whether enrollment was planned to support the stated equivalence aim.

Most importantly for interpretation, no equivalence margin or formal between-arm analysis is reported. The posted means and arm-specific confidence intervals cannot answer whether the interventions meet a defined equivalence criterion. The record does not report secondary outcomes, an overall image-quality measure, or a diagnostic-performance result. Safety reporting is limited to the posted counts, without details on ascertainment period or event definitions. These limitations restrict conclusions to descriptive interpretation of the recorded summaries.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effects of Sublingual and Transdermal Administration of Nitroglycerin for Coronary CT Angiography on Image Quality — NCT02961946.
• Registry record last updated 2019-09-17; status last verified 2019-08.
• Results first posted 2019-09-17.
• 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.

18. Record Summary

The registry record describes a completed, randomized, single-masked, parallel-group, phase 4 study of nitroglycerin for cCTA, sponsored by Massachusetts General Hospital. It lists enrollment of 198 and compares sublingual spray, sublingual tablet, and skin patch administration. The primary outcome is mean coronary artery diameter change in fold-change units, measured on the day of administration.

Posted arm means are 1.14 for spray, 1.13 for tablet, and 1.15 for patch, each with a 95% confidence interval and 66 participants listed. The record does not report a formal comparison, equivalence margin, or statistical analysis plan. It lists zero serious adverse events, zero other adverse events, and zero deaths for each group. Interpretation is therefore descriptive: the registry record does not establish equivalence or a treatment difference.