Topical Radial Artery Vasodilation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Topical Radial Artery Vasodilation (NCT01155167), a randomized phase 2, phase 3 study. The primary outcome is Change in Radial Artery Diameter.

2. Clinical Question

The clinical question concerns whether topical administration of a nitroglycerin and lidocaine combination is associated with a different change in radial artery diameter than placebo in patients undergoing cardiac catheterization through the radial artery. The registry describes the aim as facilitating radial artery access and records the investigators’ hypothesis that the topical combination would reduce radial artery spasm. The primary endpoint, however, is change in diameter, not a direct measure of successful access or spasm.

The registry lists radial artery spasm during catheterization and radial artery patency as secondary outcomes. The posted primary outcome is a continuous measurement, reported as a mean percent change. The trial enrolled 86 participants, while the primary outcome summaries list 40 in the placebo arm and 43 in the Topical Dilator arm. The registry record does not explain the difference between the enrollment total and the arm counts shown for this outcome. The question addressed by the posted comparison is therefore narrower than the study’s stated access-related aim: it concerns the measured artery-diameter change, rather than establishing whether access was easier or whether spasm was prevented.

3. Trial Design

The registry describes a randomized, parallel-group trial with quadruple masking and lists both Phase 2 and Phase 3. It records 86 participants enrolled and a completed status. The study start is listed as 2010-07 and primary completion as 2011-08. The sponsor is the University of California, San Francisco. The two listed interventions are nitroglycerin and lidocaine, classified as a drug, and placebo, classified as other.

Participants were randomized to topical nitroglycerin plus lidocaine or placebo according to the brief study description. The posted arm names are Placebo and Topical Dilator. The registry’s arm descriptions are blank, so the formulation details, application procedure, and other arm-specific protocol details are not reported in the registry record. The registry also does not report the randomization method, allocation-concealment procedures, or the practical steps used to maintain masking. “Quadruple” is the recorded masking level; the identities of the masked roles are not reported in the registry record.

Random allocation is intended, in general, to make treatment groups comparable on average with respect to characteristics that could affect an outcome. Masking is intended, in general, to reduce the influence of treatment knowledge on care, measurement, and assessment. Those are general design aims, not evidence that every source of bias was eliminated in this trial. The recorded parallel model means the arms are treated as separate groups for the comparison, rather than as a crossover in which each participant receives both interventions.

The primary outcome is reported for 40 placebo participants and 43 Topical Dilator participants. The record does not report why those outcome counts differ from the total enrollment or whether any participants were excluded from the endpoint analysis. A detailed protocol and the trial’s original sample-size justification are not reported in the registry 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.

Before assignment: 3 participants from the placebo group were excluded (2 secondary to insufficient or uninterpretable ultrasound data and 1 secondary to patient's access site change from transradial access (TRA) to femoral access).

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 Change in Radial Artery Diameter, measured over Baseline and after 30 minutes of drug application.

The primary endpoint is change in radial artery diameter, expressed as percent change, from baseline to a measurement after at least 30 minutes of topical cream application. The registry describes ultrasound measurement of the radial artery at a location 2 cm proximal to the radial styloid process. It says the cross-sectional radial artery area was measured using a high-frequency linear array transducer, that each measurement was performed 3 times and averaged, and that the later measurement was made in the same fashion. The endpoint title refers to diameter, while the measurement description refers to cross-sectional area; additional details reconciling that wording are not reported in the registry record.

A continuous measure can retain information about the amount and direction of change, rather than reducing the outcome to a yes-or-no event. In general, a percent-change endpoint expresses change relative to a baseline measurement, which can aid comparison across measurements with different starting values. The registry identifies the endpoint as a mean and reports a standard deviation for each arm, allowing a comparison of group averages and the spread of participant measurements.

The biological and procedural rationale recorded in the registry is to facilitate radial artery access and reduce spasm. Diameter change is relevant to that rationale because it describes a measured change in the artery. It is not, by itself, a direct outcome of successful access, spasm, patency, or a patient’s clinical course. Those distinctions matter when interpreting the result: the primary endpoint answers a measurement question, while the study’s broader motivation concerns access and spasm. The timeframe and measurement description are reported, but the primary population field is blank.

7. Results Posted in the Registry

• Topical Dilator: mean 16.50 versus -5.60 on control; difference 22.10 (95% CI 20.69 to 23.51), standardized effect d = 6.58; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous, and the registry says it is summarized as a mean with a standard deviation. A mean describes the center of a set of measurements. A standard deviation describes how dispersed individual measurements are around that mean; it is not the uncertainty interval for the mean. General explanation: the standard error instead describes the sampling uncertainty in an estimated mean, and a confidence interval combines that uncertainty with a chosen confidence level and a statistical procedure.

What does the mean difference represent?

The comparison is expressed as the mean difference between the Topical Dilator arm and placebo. The reported means are 16.5 and -5.6, respectively, and the recalculated unadjusted mean difference is 22.1. This summarizes the contrast in average percent change on the endpoint scale. It does not describe the difference for every participant: individual responses can vary, and the reported arm standard deviations describe that variation. The registry does not report an adjusted mean difference from a model incorporating other variables.

Why distinguish the estimate from its p-value?

The estimate describes the magnitude and direction of the average contrast. The confidence interval describes uncertainty around that estimate under the calculation’s assumptions. A p-value addresses how compatible the observed data are with a specified no-difference model under the test assumptions. These quantities answer related but distinct questions. General explanation: a small p-value does not by itself say whether an effect is clinically important, and it does not give the probability that a treatment is effective. The posted unadjusted p-value is < 0.001, while the effect estimate and confidence interval provide the scale and precision of the contrast.

The confidence interval reported for the mean difference is 20.69 to 23.51. The recalculation is an unadjusted comparison based on the posted summary statistics. It is not described as a covariate-adjusted or otherwise model-based sponsor analysis. The registry record reports no analysis entries, so details about the original statistical procedure, including its treatment of the measurements and any prespecified modeling choices, are not reported in the registry record. The posted interval and p-value should be understood in that limited context.

What does randomization contribute?

Random assignment is designed, in general, to reduce systematic differences between groups at the start of a trial. If allocation is implemented as intended and follow-up and analysis are handled appropriately, the comparison can support an estimate of the effect of assignment to the study arms. Randomization does not guarantee that the observed groups will be identical on every characteristic, nor does it remove concerns about missing outcomes, measurement, or departures from the assigned intervention. The registry records randomization but does not provide the sequence-generation or allocation-concealment details needed to assess those procedures.

The parallel model indicates that participants were assigned to one of the study arms for the comparison. The registry also records quadruple masking. In general, masking can limit the influence of treatment knowledge on participants, clinicians, outcome assessors, or other trial roles. The registry does not specify which roles were masked or how masking was maintained, so those implementation details cannot be evaluated from the record.

Why can over-dispersion matter?

General explanation: a statistical model may assume a particular amount of variability in the data. If the actual variability is greater than the model allows, a model can make estimates appear more precise than they are, leading to confidence intervals that are too narrow or tests that are too optimistic. For a continuous endpoint, examining the spread of measurements and the suitability of the model is part of assessing precision. The posted arm standard deviations are 2.1 and 4.2; the registry does not report an analysis of distributional assumptions, residual variation, or over-dispersion. That absence does not establish that the assumptions were violated; it means the record does not document how they were assessed.

The endpoint description says each ultrasound measurement was performed 3 times and averaged. General explanation: averaging technical repeats can reduce some measurement noise, but it does not mean that the trial has repeated independent observations for each participant. The participant remains the unit represented in the arm counts unless the analysis description states otherwise. The registry does not describe how the baseline and later measurements were incorporated into the calculation beyond defining the outcome as change and reporting arm means and standard deviations.

These distinctions are important because summary statistics permit a straightforward unadjusted comparison, but they do not reveal all choices in the original analysis. The registry does not report an analysis plan, prespecified model, missing-data method, interim-analysis plan, or multiplicity procedure. The posted statistical evidence therefore supports interpretation of the reported contrast on its own terms, not assumptions about unreported design or analysis decisions.

10. Confidence Intervals and Precision

The recalculated unadjusted mean difference is 22.1 percentage points, with a 95% confidence interval from 20.69 to 23.51. The interval describes uncertainty in the estimated contrast under the recalculation’s assumptions and the posted summary statistics. It does not describe the range of individual participant responses, which is instead reflected partly by the arm standard deviations of 2.1 for placebo and 4.2 for Topical Dilator.

General explanation: a confidence interval is a procedure that, over repeated studies under its assumptions, would capture the underlying parameter at the stated rate. For an individual study, it is best read as a range of values reasonably compatible with the data and method, rather than as a probability statement about the fixed true effect. The interval does not account for uncertainties that the calculation does not include, such as unreported selection, missing-data, measurement, or analysis issues.

The interval lies above zero, consistent with the positive direction of the estimated difference. Its endpoints are fairly close to the estimate, indicating limited sampling uncertainty under this calculation, but interval width alone does not settle whether the difference matters clinically. The endpoint is a measured change in diameter, not a direct measure of successful catheter access or spasm. Precision in the surrogate measurement should not be conflated with certainty about those other outcomes.

The record does not report a sponsor analysis or details of a prespecified confidence-interval method. The interval is therefore described as a recalculated, unadjusted estimate from the posted summaries. No discrepancy is flagged in the record, but that does not supply missing protocol or analysis details. The count of participants contributing to each endpoint summary and the reason for the difference from total enrollment are also not explained.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. The illustration assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It uses the observed effect as its reference and considers planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. These are planning scenarios, not a reconstruction of the trial’s original design. The original sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the modeled number of participants per arm for an 80% chance of detecting the specified effect under the illustration’s assumptions, if that effect were the true effect. The 90% power column gives the corresponding modeled number per arm for a 90% chance. Power is a property of a planned test under assumptions; it is not the probability that a result is true. In this illustration, the listed counts are 1 per arm for both power targets when planning for 100% and 75% of the observed effect, and 2 per arm for both targets when planning for 50% of the observed effect.

Smaller effects generally require more participants to detect, because a smaller signal is harder to distinguish from random variation. The listed counts are unusually small in relation to the actual trial enrollment, which emphasizes how strongly the illustration depends on the very large observed contrast and its assumptions. They should not be read as evidence that the trial had adequate power for every outcome or as observed power. The registry’s original enrollment planning rationale is not reported. The planning curve expresses the same relationship between the effect size being targeted and the modeled sample size; it is a design aid, not a forecast of the trial’s observed result.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 22.100; pooled standard deviation σ = 3.357.
2. n = 2 × (1.96 + 0.842)² × 3.357² / 22.100² = 0.4, rounded up to 1 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 22.1                      # observed difference in means
sigma <- 3.3570820663189                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1155167)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 1 (80% power), 1 (90% power)
 75% of observed effect: n per arm = 1 (80% power), 1 (90% power)
 50% of observed effect: n per arm = 2 (80% power), 2 (90% power)
power.t.test: 1.9 
Simulated power at n = 1 per arm: NA (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome of change in radial artery diameter and two secondary outcomes: radial artery spasm during catheterization and radial artery patency. It reports 3 outcome measures, while the listed secondary outcomes number 2. The record does not provide a complete mapping of all outcome measures to analyses or explain whether multiple time points, subgroups, or additional comparisons were considered.

When several outcomes or comparisons are tested, the chance of obtaining at least one apparently unusual result can increase. General explanation: multiplicity procedures can control that risk, but their use and their effect on reported uncertainty depend on the prespecified analysis plan. A multiplicity adjustment, hierarchical testing strategy, or other correction is not reported in the registry record. The posted p-value is unadjusted, and it should not be interpreted as though a correction had been documented.

The registry reports no analysis entries. It does not report the analysis population, whether participants were analyzed according to randomized assignment, how missing endpoint measurements were handled, or whether any observations were excluded. The difference between the overall enrollment of 86 and the primary outcome counts of 40 and 43 is not explained. Without this information, the impact of missing measurements or exclusions cannot be assessed.

Details about interim analyses, stopping rules, prespecified covariates, protocol deviations, and the statistical analysis plan are not reported in the registry record. These omissions do not show that the procedures were absent; they limit what can be evaluated from the registry entry. The primary comparison is therefore best read as the posted unadjusted comparison of the available arm summaries, with no documented multiplicity or missing-data strategy to add to its interpretation.

14. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

The posted serious adverse event figures list 0 affected participants among 43 at risk in the placebo group and 0 among 43 at risk in the Topical Dilator group. For other adverse events, the figures list 0 affected among 40 at risk in the placebo group and 0 among 43 at risk in the Topical Dilator group. The at-risk counts differ between the serious and other adverse event categories for placebo.

These entries describe the counts recorded in the registry categories; they do not establish that no adverse experiences of any kind occurred. The registry record does not list serious adverse event terms, and the death entries are null, so death counts are not reported in the registry record. The record does not explain the different at-risk denominators, the period over which events were collected, or the event-collection procedures. A zero in a posted category should be interpreted as no affected participants recorded in that category, rather than as proof of no risk.

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

The primary result shows a positive unadjusted difference in mean percent change in radial artery diameter between the Topical Dilator and placebo arms. The estimated mean difference is 22.1 percentage points, with a 95% confidence interval from 20.69 to 23.51 and a posted unadjusted p-value of < 0.001. The arm summaries show a mean change of 16.5 for Topical Dilator and -5.6 for placebo. These figures describe the endpoint as reported; they do not show the result for every participant.

The result does not, by itself, establish that topical nitroglycerin and lidocaine improve the success of radial artery access, prevent radial artery spasm, or affect patency. Those outcomes are distinct from the measured diameter change. Although spasm and patency are listed as secondary outcomes, their results are not reported in the posted summaries represented by these registry entries. The registry’s stated aim and hypothesis explain why the diameter measure was of interest, but they do not substitute for results on the access-related outcomes.

The estimated contrast is statistically distinguishable from zero under the unadjusted calculation, but statistical evidence is not the same as clinical importance. The registry does not specify a threshold for a clinically meaningful change in diameter, nor does it report how diameter change relates to procedural outcomes. No medical recommendation follows from this statistical summary.

Interpretation is also limited by absent information about the original analysis plan, the endpoint analysis population, missing measurements, and the explanation for the difference between enrollment and endpoint counts. The record identifies randomization and quadruple masking, but does not detail how either was implemented. The findings should therefore be read as a comparison of the posted group summaries, not as a complete account of every trial procedure or outcome.

16. Why This Trial Matters Statistically

This trial illustrates the distinction between a study’s motivating clinical question and the endpoint used to address it. The stated aim concerns facilitating radial artery access, and the stated hypothesis concerns reducing spasm. The primary endpoint is percent change in radial artery diameter. Statistical interpretation must keep those concepts separate: a group contrast in a continuous anatomical measurement does not automatically establish a change in access success, spasm, or patency.

It also illustrates why effect estimates and uncertainty measures should be read together. The mean difference of 22.1 gives the scale and direction of the observed contrast, while the confidence interval from 20.69 to 23.51 conveys uncertainty under the unadjusted calculation. The p-value, < 0.001, answers a different question about compatibility with a no-difference model. None of these quantities alone determines clinical importance or resolves limitations in the registry record.

Finally, the contrast between 86 enrolled participants and the endpoint arm counts of 40 and 43 highlights the value of transparent reporting about analysis populations and missing outcomes. The registry identifies the randomized, parallel, quadruple-masked design, but does not document key analysis decisions, multiplicity handling, or the original sample-size rationale. These omissions do not invalidate the posted result; they define the boundaries of what can be assessed. The planning illustration further shows how sample-size requirements depend on the effect targeted and the assumptions used, rather than serving as evidence about the trial’s original planning or its observed power.

17. 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 leaves several trial-specific details unavailable. The primary population field is blank, and further eligibility criteria are not reported. Although randomization and quadruple masking are recorded, the allocation procedure, concealment method, identities of masked roles, and masking-maintenance procedures are not described. Arm descriptions are blank, so formulation and application details beyond the named topical combination are not reported.

The primary outcome description refers to measuring cross-sectional radial artery area, while the endpoint title and summary identify change in radial artery diameter. The registry does not explain the relationship between those descriptions or provide the underlying participant-level measurements. It reports that the measurement was taken at baseline and after at least 30 minutes of application, but does not provide a more detailed schedule or assessment of measurement reliability.

The record does not explain why the primary outcome counts are 40 for placebo and 43 for Topical Dilator when enrollment is 86. It does not report an analysis population, missing-data method, exclusions, protocol deviations, or an analysis plan. The outcomes of radial artery spasm and patency are listed, but their results are not reported in the posted outcome summaries. The adverse-event entries contain zero affected participants in the listed categories, but do not explain the denominators or event-collection period; deaths are not reported in the registry record.

Finally, the record does not provide the trial’s original sample-size justification, interim-analysis plan, or multiplicity procedure. These reporting limitations restrict assessment of the full protocol and analysis choices. They should not be turned into assumptions that a procedure was or was not conducted.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Topical Radial Artery Vasodilation — NCT01155167.
• Registry record last updated 2018-09-25; status last verified 2013-05.
• Results first posted 2013-05-15.
• 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.

21. Record Summary

NCT01155167, titled “Topical Radial Artery Vasodilation,” is recorded as a completed randomized, quadruple-masked, parallel trial with Phase 2 and Phase 3 designations. The sponsor is the University of California, San Francisco. Enrollment is listed as 86. The registry describes topical nitroglycerin plus lidocaine versus placebo in patients undergoing cardiac catheterization via the radial artery.

The primary outcome is change in radial artery diameter, reported as percent change from baseline to after at least 30 minutes of application. The posted arm summaries include 40 placebo participants and 43 Topical Dilator participants. The recalculated unadjusted mean difference is 22.1 percentage points, with a 95% confidence interval from 20.69 to 23.51; the posted unadjusted p-value is < 0.001.

Radial artery spasm and patency are listed as secondary outcomes, but their results are not reported in the posted summaries. The registry record does not explain the difference between enrollment and primary outcome counts or provide a detailed statistical analysis plan.