Control of Tourniquet Pain With an Axillary Ring of Subcutaneous Local Anesthetic: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Control of Tourniquet Pain With an Axillary Ring of Subcutaneous Local Anesthetic (NCT01829399), a randomized phase 4 study. The primary outcome is Time in Minutes That Tq Remained Inflated.

2. Clinical Question

The study addresses tourniquet pain despite regional anesthesia of the upper extremity. The registry describes the proposed purpose as assessing whether a subcutaneous local-anesthetic ring on the inner upper arm could diminish tourniquet pain. It gives the broader rationale that this might allow distal nerve blocks to be used as the primary anesthetic for hand or forearm surgery, while noting possible advantages of those blocks. That rationale is not itself an outcome tested by the posted primary results.

The direct statistical question is narrower: whether the observed mean duration of tourniquet inflation differed between the two first-visit groups, and how precisely each group mean was estimated. The record reports means and 95% confidence intervals, but no inferential comparison result. The posted results therefore describe the groups; they do not establish a quantified treatment contrast or answer every clinical question motivating the study.

3. Trial Design

The registry identifies this as a randomized, quadruple-masked, phase 4 crossover study. Participants were assigned to a first intervention of either bupivacaine with epinephrine or saline, injected as a subcutaneous axillary ring. The tourniquet was inflated 15 minutes after injection. The posted primary results separate the first-visit bupivacaine and saline groups, with 12 participants in each reported group.

The study description says that each participant was intended to receive the opposite injection later on the same arm, with the second assessment approximately one month after the first. The primary outcome description states that a strong crossover effect led to analysis of data from the first intervention only. Accordingly, the reported first-visit comparison does not use the within-participant comparison that is often central to a crossover analysis. No specific details about the nature of the crossover effect or its assessment are reported in the registry record.

The study summary describes randomization into four groups and refers to twenty volunteers, while the registry enrollment field reports 24. The results list 12 participants in each first-visit group. The record does not explain the differing enrollment descriptions, so they should not be reconciled by assumption.

The record labels the study completed. Its masking designation is quadruple, but the identities of the masked roles are not reported in the registry record. Details of sequence generation, allocation concealment, protocol deviations, and the handling of withdrawals are also not reported. Those omissions limit how fully the conduct of the trial can be evaluated from the registry information alone.

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.

Visit 1

Visit 2 (One Month Later)

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 Time in Minutes That Tq Remained Inflated, measured over Tq was inflated 15 minutes after injection of Bupivacaine or placebo and remained inflated until subject could no longer tolerate it. Maximum allowable inflation time per session was 60 minutes..

The primary endpoint is the time in minutes that the tourniquet remained inflated. According to the registry, inflation began 15 minutes after injection and continued until the subject could no longer tolerate it. The tourniquet was inflated to 100 mm Hg over the subject’s systolic blood pressure. A maximum allowable inflation time per session was 60 minutes.

This endpoint translates tolerance into a continuous measure of elapsed time. A longer recorded duration means the tourniquet remained in place longer before the participant reached the stopping point specified in the study description. This makes the outcome a direct measure of the study’s stated question about tourniquet discomfort, but it does not measure every aspect of pain or function.

The posted results report the mean duration for each first-visit group, with a 95% confidence interval for each mean. A mean provides a summary of the group’s recorded durations; the confidence interval conveys uncertainty around that estimated mean. The record does not report the individual observations, a measure of within-group spread, or a treatment-effect estimate with its own confidence interval. Therefore, the group summaries alone do not show the distribution of participant responses or quantify the uncertainty in a between-group contrast.

The registry also lists pain score at tourniquet deflation as a secondary outcome. Its result values are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean summarize?

A mean is the arithmetic average of the recorded values in a group. For this outcome, the values are durations of tourniquet inflation. A mean can provide a compact description of a group, but it does not reveal whether observations cluster near that value or whether some are much shorter or longer. Individual observations and a measure of spread would help characterize that distribution; those details are not reported in the registry record.

The posted mean for the bupivacaine first-visit group is 30.5 minutes, and the mean for the saline first-visit group is 22.4 minutes. They describe separate groups assigned to different first interventions. The record does not provide a direct estimate of the between-group difference or an inferential test for that contrast. No new contrast should be inferred from the means alone.

What does a confidence interval communicate?

A confidence interval is a statistical way to express uncertainty around an estimate. In general, a 95% confidence interval is generated by a procedure that, under its assumptions, would cover the target parameter in 95% of repeated samples. It is not a statement that there is a 95% probability that this particular fixed parameter lies inside the interval, nor is it an interval for most individual observations.

The registry reports a 95% confidence interval of 26.1 to 35.0 minutes for the bupivacaine group mean, and 18.0 to 26.9 minutes for the saline group mean. These intervals quantify uncertainty around each group’s mean as reported. They do not directly give the uncertainty around a contrast between the groups. The record does not state the method used to calculate the intervals, so details such as distributional assumptions or any adjustment cannot be evaluated.

Why does the crossover design matter?

In a crossover study, a participant can receive more than one intervention in separate periods. A paired analysis can compare each participant’s response under the different conditions, thereby accounting for stable participant characteristics that influence the outcome. Such an analysis must also consider effects of treatment order and whether an earlier intervention affects a later period.

The registry says this study planned an opposite injection on the same arm approximately one month after the initial experiment. It also says that, because of a strong crossover effect, only data assessed from the first intervention were analyzed. The reported results therefore use the first-visit groups and do not present a paired estimate. The registry does not report the analysis method used to assess the crossover effect or describe its source. A first-period analysis avoids relying on the later period, but it does not provide the within-participant comparison that a full crossover analysis could offer.

What does randomization contribute?

Random allocation is intended to make the assigned groups comparable on average with respect to measured and unmeasured characteristics, rather than allowing participants or investigators to choose the assignment. In a small study, randomization does not guarantee that all relevant characteristics are balanced. The registry identifies the allocation as randomized but does not report the sequence-generation or concealment procedures. The record also identifies quadruple masking, without specifying which roles were masked.

How should the stopping rule and time limit be understood?

The measured time ended when the subject could no longer tolerate the tourniquet; the maximum allowable inflation time per session was 60 minutes. This makes the outcome dependent on both the participant’s tolerance and the study’s stated stopping procedure. A maximum time can constrain the values that could be observed. The registry does not report how many participants reached the maximum, so the degree to which the cap affected the results is unknown.

More generally, if a meaningful number of observations are stopped at a maximum, the resulting times may not describe the full duration participants might otherwise tolerate. That is a general consideration, not a claim about what occurred in this study. The record does not provide individual durations, making it impossible to assess the shape of the outcome distribution or the presence of values at the cap.

What is not available for inferential interpretation?

The record contains group means and confidence intervals but no posted analysis count, p-value, or confidence interval for a between-group effect. General statistical practice distinguishes estimation from testing: an estimate describes the size of an effect, while a test evaluates how compatible the data are with a specified null hypothesis under a model. Neither the null hypothesis nor a statistical model for a direct treatment comparison is reported.

The record also does not report a statistical analysis plan, sample-size justification, interim analyses, or adjustments for multiple comparisons. These items should not be inferred from the randomized design or from the presence of confidence intervals. A planning illustration based on an observed effect, when available, is not observed power and does not replace a trial’s original design justification. No planning sample-size results are stated in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one secondary outcome: pain score at tourniquet deflation. Its result values are not reported in the registry record. The primary outcome is time in minutes that the tourniquet remained inflated. Although the record identifies these outcomes, it does not report a statistical analysis plan describing which comparisons were planned, how outcome measures were prioritized, or whether any multiplicity adjustment was intended.

Multiplicity arises when several outcomes, time points, groups, or statistical comparisons are examined. In general, repeated testing can increase the chance of obtaining an apparently notable result by chance. Whether and how this concern applies depends on the planned analyses and their interpretation; those details are not reported. No adjustment should be assumed.

There are no posted analyses listed in the record. The primary group means and confidence intervals are reported, but no direct inferential comparison is given. The record does not report missing outcome counts, reasons for missingness, exclusions, protocol deviations, or whether the analysis followed an intention-to-treat or another defined population. It also does not state how missing data were handled.

The enrollment description in the study summary and the enrollment field differ: the summary refers to twenty volunteers, while the field reports 24. The first-visit results list 12 participants in each group. The registry does not explain these descriptions or identify whether any enrolled participants lacked primary outcome data. These gaps restrict assessment of completeness and of the analysis population.

11. 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 0% reporting threshold.

The registry reports zero serious adverse events among 12 participants at risk in the bupivacaine group and zero among 12 participants at risk in the saline group. It also reports zero other adverse events among 12 participants at risk in each group. These are the adverse-event counts recorded for the listed groups and should be interpreted within the scope of the registry entry.

A zero count means no events of the specified category were reported for the participants at risk in that group. It does not establish that an event is impossible, that every possible symptom was assessed or reported, or that there is no safety difference between interventions. With a limited number of participants, uncommon events may not be observed. The registry record does not provide event definitions, surveillance details, or a comparison analysis for adverse events.

Death counts are not reported in the registry record. The absence of reported death figures should not be converted into a claim about mortality. These safety summaries are descriptive and do not support broader conclusions about safety beyond the adverse-event information recorded for this study.

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

The posted results show that the mean time the tourniquet remained inflated was 30.5 minutes for the first-visit bupivacaine group and 22.4 minutes for the first-visit saline group. The record also reports a 95% confidence interval around each group mean. This is a descriptive account of the observed first-intervention results under the study’s procedure.

The results do not include a direct estimate of the difference between interventions, a confidence interval for that difference, or a p-value. Consequently, the record does not quantify the precision of a treatment contrast or report a formal test of that contrast. The separate intervals around the group means should not be treated as if they were the interval for the difference.

The result concerns time to participant intolerance of an upper-arm tourniquet in the study setting. It does not directly establish effects on pain scores, since the secondary pain-score result is not reported. Nor does it answer whether particular nerve-block approaches can be used as primary anesthesia, whether they have fewer complications, or whether postoperative arm control differs. Those points appear as rationale in the study summary, not as outcomes established by the posted primary results.

The intended crossover component is also important. Because the registry says a strong crossover effect led to use of first-intervention data only, the posted primary results are not a full within-participant comparison across both interventions. The record does not explain the crossover effect sufficiently to assess its source or consequences in greater detail.

Finally, the findings should be interpreted alongside the limited information about study conduct and analysis. The registry does not report a statistical analysis plan, a sample-size justification, missing-data handling, the distribution of participant-level durations, or the number reaching the 60-minute limit. Those omissions prevent stronger conclusions about the robustness, generalizability, and clinical implications of the observed group summaries.

13. Why This Trial Matters Statistically

This study illustrates why design labels alone do not determine the analysis available to readers. A crossover design can support comparisons within the same participant, but the registry states that the primary analysis used only the first intervention because of a strong crossover effect. Readers therefore need to distinguish the intended crossover structure from the first-period results that were actually posted.

It also demonstrates the difference between reporting group summaries and reporting a treatment contrast. Means and confidence intervals help describe each group, but they do not supply the uncertainty around a direct comparison. A clear estimate and interval for the contrast would answer a different statistical question from separate intervals for the two means. No such comparative estimate is reported in the registry record.

The endpoint is a time measure with a defined participant-based stopping rule and a maximum allowable duration. This raises general questions about censoring or truncation when a maximum is reached, and about how a stopping decision relates to the underlying experience of discomfort. The record does not say whether any observations reached the cap, so these are considerations for interpretation rather than assertions about the data.

Finally, reporting inconsistencies and missing analysis details matter. The study summary refers to twenty volunteers, while the enrollment field reports 24, and the record does not explain the difference. With no reported analysis plan or missing-data account, readers cannot fully reconstruct how the posted results relate to the intended study. This makes transparent reporting of the analysis population, endpoint handling, and treatment-effect uncertainty especially important.

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 main limitation of the posted primary results is that they are first-intervention summaries rather than a full crossover comparison. The registry attributes this to a strong crossover effect but does not define or explain that effect. It is therefore not possible to evaluate from the record how the later period was affected or how the decision to exclude it influenced the interpretation.

The record reports group means and confidence intervals but not a direct between-group estimate, its confidence interval, or a p-value. It also does not state the confidence-interval calculation method, provide individual values or a within-group spread measure, or report how many durations reached the 60-minute maximum. These omissions limit assessment of distribution, precision of the contrast, and possible influence of the cap.

The registry enrollment field reports 24, while the study summary refers to twenty volunteers. The first-visit groups each report 12 participants, but the difference in enrollment descriptions is not explained. The record does not report missing outcome counts, exclusions, withdrawals, protocol deviations, or the analysis population definition.

Further limitations of the available record include no reported sample-size justification, statistical analysis plan, interim-analysis information, or missing-data methods. Masking is labeled quadruple, but the masked roles are not identified. The secondary pain-score result is not reported, and safety information lacks reported death counts and event-collection details. These points describe limits of what is available in the registry record; they do not establish that the trial itself lacked procedures or analyses that were not recorded.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Control of Tourniquet Pain With an Axillary Ring of Subcutaneous Local Anesthetic — NCT01829399.
• Registry record last updated 2015-10-22; status last verified 2015-10.
• Results first posted 2015-10-22.
• 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 describes a randomized, quadruple-masked, phase 4 crossover study comparing a subcutaneous axillary ring of bupivacaine with epinephrine against normal saline for tourniquet tolerance. The primary outcome was time in minutes until the participant could no longer tolerate tourniquet inflation, subject to a 60-minute maximum.

The posted first-visit results report a mean of 30.5 minutes for bupivacaine, with a 95% confidence interval of 26.1 to 35.0, and a mean of 22.4 minutes for saline, with a 95% confidence interval of 18.0 to 26.9. The registry says only first-intervention data were analyzed because of a strong crossover effect. No direct inferential comparison is reported. A secondary pain-score outcome is listed, but its values are not reported in the registry record. The record reports zero serious and other adverse events in the listed groups; death counts are not reported.