Duration of Analgesia After Popliteal Fossa Nerve Blockade: Effects of Dexamethasone and Buprenorphine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Duration of Analgesia After Popliteal Fossa Nerve Blockade: Effects of Dexamethasone and Buprenorphine (NCT01277159), a randomized na study. The primary outcome is Time it Takes for Nerve Block to Wear Off.

2. Clinical Question

3. Trial Design

The registry describes a randomized, triple-masked, parallel-group trial. It lists the study as completed, with enrollment of 108. The listed start was 2010-10 and primary completion was 2011-12. The sponsor was Hospital for Special Surgery, New York. The phase is listed as NA.

Five intervention regimens are described. The reference regimen was a control nerve block with IV dexamethasone (4 mg). One other group received a nerve block with dexamethasone (4 mg) and IV saline. A third received the control block with IV dexamethasone (4 mg) and IV buprenorphine (0.3 mg). Another received a nerve block with buprenorphine (0.3 mg) and IV dexamethasone (4 mg). The final regimen combined dexamethasone (4 mg) and buprenorphine (0.3 mg) in the nerve block, with IV saline.

The primary outcome was continuous: time until the nerve block wore off, in hours, summarized as a mean and standard deviation. Its timeframe was up to 72 hours. Posted outcome arm counts range from 16 to 21, with arm-specific means from 30.4 to 45.6 hours. The registry lists enrollment of 108 separately; reconciliation between that enrollment figure and the outcome counts is not reported in the registry record.

The registry summary places the study within a postoperative multimodal analgesic pathway. It notes that patients scheduled to go home after ankle surgery typically receive a popliteal fossa sciatic nerve block and oral analgesic tablets, and that pain may return after the block wears off. The registry record does not report the randomization procedure, masking procedures, the trial's original sample-size justification, or a detailed statistical analysis plan.

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 Time it Takes for Nerve Block to Wear Off, measured over up to 72 hours.

The primary endpoint was the time it takes for the nerve block to wear off, measured in hours and assessed over a timeframe of up to 72 hours. The registry reports a mean and standard deviation for each arm. The arm means describe the average observed duration of analgesia in each group; the standard deviations describe how much individual observations varied around those means.

Time until a block wears off is used because the study question is whether the tested regimens prolong analgesia from the popliteal fossa nerve block. It expresses duration directly in a clinically interpretable time unit. General statistical context: a continuous endpoint such as time in hours can be summarized by its mean when the target is the average duration, while its spread conveys whether individual participants had similar or widely varying durations.

The registry does not give a more detailed operational definition of when a block counted as worn off, such as a pain threshold or assessment procedure. That definition, the assessment schedule, and the handling of participants whose block had not worn off by the end of the up-to-72-hour timeframe are not reported in the registry record. Those details matter for understanding precisely how the endpoint was measured and how the stated timeframe affected the analysis.

7. Results Posted in the Registry

• Nerve Block With Dexamethasone (4 mg). IV Saline.: mean 45.10 versus 30.40 on control; difference 14.70 (95% CI 11.41 to 17.99), standardized effect d = 2.85; z-test p = <0.001.
• Control Nerve Block. IV Dexamethasone (4 mg). IV Buprenorp: mean 32.20 versus 30.40 on control; difference 1.80 (95% CI -1.86 to 5.46), standardized effect d = 0.32; z-test p = 0.335.
• Nerve Block With Buprenorphine (0.3 mg). IV Dexamethasone (: mean 45.60 versus 30.40 on control; difference 15.20 (95% CI 11.70 to 18.70), standardized effect d = 2.83; z-test p = <0.001.
• Nerve Block With Dexamethasone (4 mg) / Block Buprenorphine: mean 45.60 versus 30.40 on control; difference 15.20 (95% CI 11.46 to 18.94), standardized effect d = 2.79; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean difference represent?

General statistical explanation: a mean difference compares the average outcome in one group with the average in a reference group. For this trial, the outcome is time until the nerve block wore off, in hours. A positive mean difference indicates that the comparison group's mean duration was higher than the reference group's mean. The recalculated differences are unadjusted: they use the posted group summaries without accounting for covariates or other design features. They should not be confused with an adjusted estimate from a prespecified model.

The reference mean was 30.4 hours. Compared with it, the posted differences were 14.7 hours for the nerve block with dexamethasone and IV saline, 1.8 hours for the control block with IV buprenorphine, 15.2 hours for the nerve block with buprenorphine and IV dexamethasone, and 15.2 hours for the block containing both additives. Each difference is a separate contrast with the reference group. A difference between any pair of non-reference groups was not reported as an analysis.

What does the standard deviation describe?

General statistical explanation: the standard deviation describes spread among observations around a group mean. It is not the uncertainty in the estimated mean, and it is not a range within which all participant outcomes must fall. The posted standard deviations were 5.1 hours in the reference group, 5.2 hours in the dexamethasone-in-block group, 6.1 hours in the control-block plus IV buprenorphine group, 5.6 hours in the buprenorphine-in-block group, and 5.8 hours in the group with both additives in the block.

The standard deviation helps put a mean in context: an average alone does not show how consistently individual outcomes cluster around it. These summaries do not show the shape of the outcome distribution or whether a small number of observations strongly influenced a mean. Distributional information is not reported in the registry record.

How should p-values be read?

General statistical explanation: a p-value measures how compatible data are with a specified null hypothesis under the assumptions of the statistical test. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The unadjusted p-values were <0.001 for the three comparisons with positive mean differences of 14.7 or 15.2 hours, and 0.335 for the comparison with a mean difference of 1.8 hours. The registry record does not report a sponsor analysis or a complete test specification alongside these recalculated comparisons.

For a continuous outcome, a mean-comparison test commonly evaluates whether the population means differ, but the exact test used for the trial's own analysis is not reported in the registry record. The recalculated unadjusted figures are not a substitute for a prespecified analysis plan. Their interpretation depends on assumptions about independent observations, outcome distribution, and variance estimation. The registry record does not give enough detail to assess all such assumptions.

Why can over-dispersion matter?

General statistical explanation: over-dispersion refers to variability greater than a model assumes. It is most often discussed for count outcomes, where a model that understates variability can make standard errors too small and confidence intervals too narrow. This primary outcome is reported as a continuous duration with a mean and standard deviation, rather than as a count. Over-dispersion is therefore not the central issue in interpreting the posted mean comparisons. More generally, any mismatch between a model's assumptions and the actual variability can affect uncertainty estimates; the trial's original model and diagnostics are not reported in the registry record.

What is and is not available for the analysis?

The registry posts one primary outcome and no secondary posted outcomes. It lists outcome means, standard deviations, arm counts, and recalculated unadjusted comparisons. It does not report a detailed analysis population, participant flow, exclusions from analysis, missing outcome counts, imputation approach, covariate adjustment, interim analyses, or a prespecified multiplicity strategy. The absence of these details in the registry record should not be read as evidence that a particular procedure was or was not used in the trial.

There are five intervention regimens and several comparisons with the same reference regimen. General statistical explanation: when multiple hypotheses are tested, the chance of at least one apparently unusual result can rise if each test is interpreted separately without an adjustment or a defined testing hierarchy. Whether such adjustment is appropriate depends on the trial's aims and plan. Because the plan and any adjustment are not reported in the registry record, the individual unadjusted p-values should not be presented as if they accounted for all comparisons.

10. Confidence Intervals and Precision

The 95% confidence intervals quantify uncertainty around each recalculated unadjusted mean difference under the assumptions of the calculation. General statistical explanation: a confidence interval is a range of estimates compatible with the observed data and the method used; it is not a guarantee that the true value lies within the particular interval. Its width reflects both the observed variability and the information available in the comparison.

For the dexamethasone-in-block regimen with IV saline, the estimated difference was 14.7 hours and the interval was 11.41 to 17.99 hours. For the control block with IV buprenorphine, the estimate was 1.8 hours and the interval was -1.861 to 5.461 hours. For the nerve block with buprenorphine and IV dexamethasone, the estimate was 15.2 hours and the interval was 11.7 to 18.7 hours. For the block containing both dexamethasone and buprenorphine, the estimate was 15.2 hours and the interval was 11.46 to 18.94 hours.

The interval for the IV buprenorphine comparison includes zero and spans values on either side of no mean difference. It therefore leaves uncertainty about whether the underlying mean difference is positive or negative. The other three intervals are entirely above zero, indicating that the recalculated estimates are more precise in their direction relative to zero under this method. That distinction concerns statistical uncertainty, not clinical importance.

Outcome arm counts were 17, 21, 19, 19, and 16. These are modest arm-specific counts, and uncertainty in a mean estimate is affected by both the number of observations and their variability. The registry does not report confidence intervals for the means themselves, or an analysis that adjusts for multiple comparisons. The intervals should therefore be interpreted as unadjusted pairwise precision measures rather than simultaneous intervals covering all comparisons.

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 for 80% power and participants per arm for 90% power. They are planning illustrations based on the observed effect, not the trial's original design calculations. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The trial's own original sample-size assumptions are not reported in the registry record.

The 80% power column gives the illustrative number of participants per arm under the stated assumptions for a design with an 80% chance of detecting the specified effect if that effect were the true one. The 90% column applies the same idea with a higher target probability of detection. These are not guarantees that a future study will detect an effect, and they do not describe the probability that the posted trial result is correct. This is not observed power.

Rows for 100% of the observed effect use the full observed difference as the planning target; rows for 75% and 50% use smaller target effects. Smaller effects need more participants to distinguish them from random variation at the same significance and power targets. For example, planning for the comparison with a 1.8-hour observed difference gives 155 participants per arm for 80% power and 208 for 90% power at 100% of that observed effect. At 50% of the observed effect, the corresponding figures are 619 and 829 participants per arm. These are illustrations, not evidence that the trial had those sizes or was planned to those targets. The displayed calculations are not totals across arms.

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 = 14.700; pooled standard deviation σ = 5.156.
2. n = 2 × (1.96 + 0.842)² × 5.156² / 14.700² = 1.9, rounded up to 2 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 <- 14.7                      # observed difference in means
sigma <- 5.15579501359608                     # 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(1277159)
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 = 2 (80% power), 3 (90% power)
 75% of observed effect: n per arm = 4 (80% power), 5 (90% power)
 50% of observed effect: n per arm = 8 (80% power), 11 (90% power)
power.t.test: 3.2 
Simulated power at n = 2 per arm: 0.364 (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 one primary outcome, time until the nerve block wore off, and no secondary posted outcomes. It presents comparisons of four regimens with the control regimen. The registry record does not report whether the trial's original analysis used a prespecified hierarchy, adjusted p-values, or another procedure to account for multiple comparisons. It also does not report whether any analyses were designated exploratory.

General statistical explanation: testing several comparisons can make isolated p-values harder to interpret, because each test creates an opportunity to observe a result that appears unusual under its null hypothesis. An adjustment or testing hierarchy can be used to manage this issue, but the appropriate approach depends on the intended questions and the prespecified plan. In the absence of a reported plan, each posted unadjusted p-value is best read as an individual comparison, not as evidence that the family of comparisons was controlled at a particular error rate.

Missing-data information is limited. The registry provides arm counts for the primary outcome but does not report participant flow, missing outcome counts, reasons for missingness, or how missing values were handled. It does not state whether the analysis included all randomized participants, only participants with observed outcomes, or another analysis population. The difference between the listed enrollment of 108 and the outcome arm counts is not explained in the registry record; no cause for that difference can be inferred from the posted information.

The registry record also does not report whether the primary analysis followed intention-to-treat principles, whether any participants were excluded after randomization, or whether sensitivity analyses assessed the effect of missing data. These omissions limit the ability to evaluate how closely the reported outcome summaries represent the randomized groups and how robust the comparisons may be to assumptions about unobserved outcomes.

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 0% reporting threshold.

The adverse-event figures report zero serious adverse events and zero other adverse events in each of the five posted groups. The at-risk counts were 17 for the control nerve block with IV dexamethasone, 21 for the nerve block with dexamethasone and IV saline, 19 for the control block with IV buprenorphine, 19 for the nerve block with buprenorphine and IV dexamethasone, and 16 for the block containing both additives.

These entries describe what was posted for the adverse-event categories; they do not establish that no adverse events of any kind occurred. The registry record does not report deaths in the adverse-event data, so death information is not reported in the registry record. It also does not provide event definitions, collection methods, follow-up duration for safety, or a separate analysis comparing safety between groups.

General statistical explanation: a zero count in a group is an observation, not proof that the underlying risk is zero. With limited group sizes, uncommon events can remain unobserved. The posted figures should be read as recorded event counts within the registry's categories and at-risk groups, not as a comprehensive assessment of safety or as a basis for treatment decisions.

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

The posted results show that the three regimens involving dexamethasone in the nerve block, buprenorphine in the nerve block, or both additives in the block had mean times until the block wore off of 45.1 or 45.6 hours. Their recalculated unadjusted mean differences versus the control nerve block with IV dexamethasone were 14.7 or 15.2 hours, and their 95% confidence intervals were entirely above zero. By contrast, the regimen that added IV buprenorphine to the control nerve block had a mean of 32.2 hours and an estimated difference of 1.8 hours, with an interval that included zero.

These are comparisons of group averages, not predictions of an individual patient's duration. A mean does not indicate what every participant experienced, and the standard deviations show that outcomes varied within each group. The endpoint was assessed over a timeframe of up to 72 hours, while the registry record does not detail the event definition or explain how observations at the end of that timeframe were treated.

The findings do not establish that one regimen is best, that the observed differences are clinically important, or that the effect would be the same in other settings or populations. The comparisons do not isolate each additive's effect in a full factorial analysis, and no direct statistical contrasts between the active regimens are posted. The record does not report adjusted analyses, multiplicity handling, missing-data methods, or a detailed analysis population. Those gaps limit how far the results can be generalized or used to make claims about causal effects.

The registry summary frames the study as an investigation of whether dexamethasone and/or buprenorphine prolong analgesia from a popliteal fossa nerve block in a postoperative multimodal pathway. The posted outcome summaries address duration of the block, not all aspects of postoperative pain control, oral analgesic use, recovery, or longer-term outcomes. No secondary outcomes are posted. Statistical evidence about this endpoint should not be taken to answer questions that the registry record does not report.

16. Why This Trial Matters Statistically

This trial is statistically interesting because the intervention regimens vary both the additives and where they were administered. The reference group received a control nerve block with IV dexamethasone, while the other groups changed the block contents, added IV buprenorphine, or combined both additives in the block. That structure makes the exact contrast important: each posted difference is against one specific reference regimen, not against no block or a common untreated control.

The group means illustrate why effect estimates, uncertainty intervals, and design details should be read together. Three recalculated unadjusted comparisons had estimated mean differences of 14.7 or 15.2 hours and confidence intervals entirely above zero. The IV buprenorphine comparison had an estimated mean difference of 1.8 hours and an interval that included zero. These patterns are descriptive of the posted comparisons, but the record does not report a multiplicity strategy or direct comparisons among the non-reference regimens.

The sample-size illustrations also demonstrate how planning depends on the effect chosen for detection. Their requirements rise when planning targets are reduced from 100% to 75% or 50% of the observed effect. Because these calculations use observed effects and are not the trial's original planning assumptions, they should not be mistaken for evidence about the study's design adequacy or the probability that the observed findings will recur.

More broadly, the record shows how much interpretation depends on methodological detail. Randomization and triple masking are listed, but procedures for allocation, outcome assessment, missing data, analysis populations, and multiplicity are not described. Statistical results can be stated precisely while important uncertainties about design and analysis remain unresolved.

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 does not describe the procedure used to define when the nerve block wore off, the schedule of assessments, or the handling of participants whose block had not worn off by the end of the up-to-72-hour timeframe. These details affect interpretation of a time-based endpoint. Outcome summaries are limited to means and standard deviations, with no distributional display or information about skewness or influential observations.

The posted arm counts range from 16 to 21, and the registry lists enrollment of 108 without explaining the relationship between enrollment and the outcome counts. Participant flow, attrition, missing outcome data, and reasons for any exclusions are not reported in the registry record. The analysis population and the handling of missing values are also not reported.

Although the trial is described as randomized and triple-masked, the registry record does not explain the randomization sequence, allocation concealment, or how masking was maintained. It does not provide the original statistical analysis plan, sponsor analyses, covariate adjustments, or multiplicity procedures. The posted comparison calculations are unadjusted and should not be treated as proof that these issues were addressed in the trial analysis.

The intervention arms differ in both the agents used and their routes or placement. The posted comparisons are against the control nerve block with IV dexamethasone, and no direct tests among the other regimens are reported. The record therefore does not establish the separate contribution of each additive or the relative performance of active regimens. The primary outcome is limited to duration of analgesia from the block; no secondary outcomes are posted. Safety information is confined to the recorded serious and other adverse-event counts, with event definitions and safety follow-up details not reported in the registry record.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Duration of Analgesia After Popliteal Fossa Nerve Blockade: Effects of Dexamethasone and Buprenorphine — NCT01277159.
• Registry record last updated 2022-04-14; status last verified 2022-04.
• Results first posted 2017-08-31.
• 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

NCT01277159 is a completed randomized, triple-masked, parallel trial sponsored by Hospital for Special Surgery, New York. The registry lists enrollment of 108, a start of 2010-10, and primary completion of 2011-12. The study concerned patients undergoing ankle surgery and compared five nerve-block and medication regimens.

The primary endpoint was mean time until the popliteal fossa nerve block wore off, in hours, with a timeframe of up to 72 hours. Posted arm means ranged from 30.4 to 45.6 hours. Three recalculated unadjusted comparisons with the control nerve block and IV dexamethasone had mean differences of 14.7 or 15.2 hours, with confidence intervals above zero; the IV buprenorphine comparison had a mean difference of 1.8 hours and a confidence interval including zero. No secondary outcomes are posted. The registry record does not report the original sample-size rationale, detailed analysis plan, multiplicity handling, or missing-data methods.