Optimal Location of Nerve Block to Minimize Perioperative Opioid Administration in ACL Surgery: Comparing True Adductor Canal to Proximal Block: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Optimal Location of Nerve Block to Minimize Perioperative Opioid Administration in ACL Surgery: Comparing True Adductor Canal to Proximal Block (NCT03401450), a randomized phase 4 study. The primary outcome is Total Opioid Consumption Intraop Measured by Amounts of Morphine Equivalents.

2. Clinical Question

The clinical question is about the location of the block rather than a comparison of different local anesthetics: both groups are described as receiving bupivacaine at the same concentration and volume. The randomized design was intended to compare the two approaches in the context of ACL surgery. The posted outcome data describe average morphine-equivalent consumption for each group and a mean difference comparing the proximal block with the block within the true adductor canal.

The posted results do not establish that either location causes a particular opioid-consumption outcome. They describe the observed group summaries and the uncertainty around the estimated difference. Details such as eligibility criteria, the full analysis population definition, and how opioid administration was captured are not reported in the registry record.

3. Trial Design

This was a completed, randomized, single-blind, parallel-group phase 4 trial sponsored by NYU Langone Health. The registry record lists enrollment of 69 and ACL surgery as the condition. The study is described as prospective and involving human subjects. Its stated objective was to compare a block within the true adductor canal with a block proximal to that location and assess opioid administration during and after surgery.

Participants were assigned to one of two groups. The first received an ultrasound-guided single injection in the true adductor canal with 20 mL of 0.5% bupivacaine. The second received an ultrasound-guided single injection in the femoral triangle, proximal to the true adductor canal, with the same volume and concentration of bupivacaine. Ultrasound was described as a way to identify the adductor canal and the proximal end of the canal or apex of the femoral triangle. The registry record does not report the method used to generate or conceal the randomization sequence.

The record labels the study single-blind but does not identify which participants, clinicians, outcome assessors, or other personnel were masked. The date of study start is 2018-02-01, primary completion is listed as 2019-01-25, and status is completed. The primary outcome is total opioid consumption intraoperatively, measured as milligrams of morphine equivalents over a stated 24-hour timeframe. A secondary outcome concerns motor block or muscle weakness in the post-anesthesia care unit and in the surgeons’ clinic at 3, 6, and 12 months. The registry record does not report further design details about follow-up, allocation concealment, or the conduct of outcome assessment.

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

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 Total Opioid Consumption Intraop Measured by Amounts of Morphine Equivalents, measured over 24 Hours.

The primary endpoint is described as total opioid consumption intraoperatively, measured by the amount of morphine equivalents administered in milligrams. The listed timeframe is 24 hours, and the description also characterizes the measure as the amount administered intraoperatively in 24 hours. This wording combines an intraoperative outcome label with a 24-hour timeframe; the registry record does not provide further clarification of the measurement window.

Morphine equivalents express opioid amounts on a common scale, allowing opioid consumption to be summarized across medications in a single measure. As a continuous outcome, the registry reports a mean and standard deviation for each group. The mean describes the group’s average recorded consumption, while the standard deviation describes the spread of individual measurements around that average. These summaries address the trial’s stated question about whether block location is associated with different opioid consumption during the specified perioperative period.

The endpoint is a measure of medication administration, not a direct measure of pain, function, or longer-term recovery. The record does not describe the conversion rules used to express different opioids as morphine equivalents, nor does it give details of the data collection procedure. Therefore, the posted results can be interpreted as a comparison of the reported morphine-equivalent summaries, with those measurement details left unspecified.

7. Results Posted in the Registry

• ACB Proximal to True AC With Bupivacaine: mean 18.93 versus 23.21 on control; difference -4.28 (95% CI -10.76 to 2.20), standardized effect d = -0.40; z-test p = 0.195.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: opioid consumption is expressed as milligrams of morphine equivalents. For a continuous outcome, the registry reports each group’s mean and standard deviation, then reports a mean difference for the comparison. The comparison is oriented as proximal block relative to block within the true adductor canal. The posted estimate is -4.28 milligrams, with a 95% confidence interval from -10.76 to 2.195 milligrams.

What does the mean difference represent?

A mean difference expresses the contrast between the average outcome in two groups in the outcome’s original units. It is useful because it retains a direct interpretation: the estimate is in milligrams of morphine equivalents. The sign depends on the order of the groups in the contrast. In this registry comparison, a negative estimate means the observed average is lower for the proximal group than for the true adductor canal group. The point estimate is only one estimate from the observed data; it should be read together with its uncertainty interval.

What do the standard deviations describe?

A standard deviation describes how spread out observations are around a group mean. The posted standard deviations are 12.23 milligrams for the true adductor canal group and 9.34 milligrams for the proximal group. They describe individual-level variability, not the precision of the mean difference itself. Precision of a group estimate also depends on how many observations contribute to it. The record lists 21 and 23 participants for the two primary outcome summaries.

How should the confidence interval be read?

A confidence interval gives a range of effect estimates that are compatible with the observed data under the statistical procedure used. In repeated use of a method with its assumptions met, intervals constructed in this way have a defined long-run coverage property. For an individual trial, the interval is best read as a measure of uncertainty about the estimated difference, rather than as a probability statement that the true effect lies in this particular interval. Here, the range from -10.76 to 2.195 includes zero. It therefore does not rule out either direction of the difference at the conventional two-sided 0.05 significance level used in the sample-size planning assumptions.

What does the p-value add?

The unadjusted p-value is 0.195. A p-value measures how unusual data at least as inconsistent with a specified null model would be if that model and the test assumptions held. It is not the probability that the null is true, nor a measure of clinical importance. A result with this p-value does not establish equality between the groups. The registry record does not report whether any other inferential tests were planned or how multiple outcomes or comparisons were to be handled.

Why do sample size and variability matter?

Statistical precision generally improves when measurements are less variable or when more observations contribute, although the amount of improvement depends on the design and analysis. Greater variability makes it harder to distinguish a group contrast from random variation. The observed standard deviations show that consumption varied within both groups, while the outcome counts describe the sizes of the summaries. The registry record does not report the original sample-size justification, target effect, or assumptions used to plan enrollment, so the observed enrollment should not be treated as evidence that the trial was designed to detect a particular difference.

What assumptions underlie the displayed planning illustrations?

The sample-size illustrations use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They consider effects set to stated fractions of the observed effect. Those are planning assumptions for illustrations based on the observed effect; they are not reported as the trial’s original design assumptions. If a continuous outcome has strong skew, influential outliers, or other features that do not fit the analysis approach, the usual interpretation of a mean-based comparison can be affected. The registry record does not report distributional checks or a detailed statistical analysis plan.

In general, random assignment aims to make treatment groups comparable on average with respect to factors that might affect outcomes. It does not guarantee that all prognostic features are balanced in a particular trial, especially when groups are modest in size. The posted summaries do not give baseline characteristics or adjusted analyses, so they do not allow an assessment of covariate balance or adjustment. The comparison is therefore interpreted from the unadjusted group summaries and the reported unadjusted inferential result.

10. Confidence Intervals and Precision

The estimated mean difference is -4.28 milligrams of morphine equivalents for proximal block compared with block within the true adductor canal. Its 95% confidence interval extends from -10.76 to 2.195 milligrams. That range is important because it includes zero: the posted data are compatible with no mean difference, as well as with differences in either direction. The interval’s endpoints also span estimates that are not close to one another, indicating that the precise size of any group difference is uncertain.

The group means, 23.21 milligrams and 18.93 milligrams, are point estimates. The confidence interval concerns the contrast between means, not the range in which most individual participants’ consumption values fall. Individual variability is described separately by the standard deviations, 12.23 milligrams and 9.34 milligrams. A confidence interval should not be interpreted as a prediction interval for individual outcomes.

Precision depends on the variability of the outcome and the amount of information contributing to the comparison. The primary outcome summaries list 21 participants for the true adductor canal group and 23 for the proximal group. These counts are smaller than the overall enrollment of 69, and the reason for that difference is not reported in the registry record. No additional precision measure or adjusted confidence interval is reported.

The interval does not establish that the approaches are equivalent. Equivalence requires a prespecified margin and an analysis designed to evaluate whether the full plausible range lies within that margin; such a margin and analysis are not reported in the registry record. The confidence interval instead communicates uncertainty around the posted mean difference.

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 sample-size illustrations are planning calculations based on the observed effect, not observed power. They report the number of participants per arm for 80% power and the number of participants per arm for 90% power. The calculations use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. These are illustration assumptions and should not be confused with the trial’s original design assumptions, which are not reported in the registry record.

The rows labeled 100%, 75%, and 50% of the observed effect show planning for progressively smaller effects relative to the observed estimate. Smaller effects are harder to distinguish from random variation and therefore require more participants under these assumptions. The 80% power column gives the approximate participants per arm needed for an 80% chance of detecting the selected effect at the stated significance level if the assumptions hold. The 90% power column expresses the same idea with a higher target chance of detection, which generally requires a larger planned sample.

For this continuous outcome, the figures are participants per arm, not total events. The registry record does not report that these illustrations were the basis for the original enrollment target. Because they use the observed effect as their starting point, they are retrospective planning aids rather than a measure of whether the completed trial had adequate power. They should not be used to reinterpret the observed p-value as evidence that an effect was absent or present.

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 = -4.280; pooled standard deviation σ = 10.813.
2. n = 2 × (1.96 + 0.842)² × 10.813² / -4.280² = 100.2, rounded up to 101 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 <- -4.28                      # observed difference in means
sigma <- 10.812956513897                     # 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(3401450)
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 = 101 (80% power), 135 (90% power)
 75% of observed effect: n per arm = 179 (80% power), 239 (90% power)
 50% of observed effect: n per arm = 401 (80% power), 537 (90% power)
power.t.test: 101.2 
Simulated power at n = 101 per arm: 0.802 (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 record lists one primary outcome and one secondary outcome concerning motor block or muscle weakness. The secondary outcome is described as being assessed in the post-anesthesia care unit and in the surgeons’ clinic at 3, 6, and 12 months. It does not report the results for that secondary outcome in the posted results. The record does not state how many hypotheses were planned for testing, whether the repeated secondary assessments were to be analyzed separately, or whether any multiplicity adjustment was planned.

Multiplicity matters when several outcomes, time points, or comparisons are tested. In general, making many statistical tests can increase the chance of at least one apparently notable result arising by chance. Methods such as prespecifying a primary comparison, adjusting significance thresholds, or controlling an error rate can address that issue, but the registry record does not report whether such procedures were specified. The single unadjusted p-value posted for the primary contrast should therefore be understood as an unadjusted result; the record does not provide enough information to describe a broader testing strategy.

The record also does not report a detailed missing-data plan, imputation approach, or the analysis population definition. Although overall enrollment is 69, the primary outcome group counts are 21 and 23. The reasons those counts differ from enrollment, and whether any participants were excluded from the outcome summaries, are not reported in the registry record. It is not possible to determine from these numbers alone whether outcomes were unavailable, participants were excluded for another reason, or another accounting process was used.

Randomization does not by itself determine how participants with incomplete data should be handled. An intention-to-treat analysis, a per-protocol analysis, or another defined analysis population can lead to different interpretations, but the record does not identify which approach was used. No adjusted primary result or analysis-population description is reported. These omissions limit assessment of the robustness and scope of the posted comparison.

14. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry record lists serious adverse events among 20 participants at risk in the true adductor canal group and 23 participants at risk in the proximal block group. It reports zero serious adverse events in each group and zero deaths in each group. The record also reports zero other adverse events for the listed at-risk groups.

These figures describe events recorded in the registry, not proof that no adverse events occurred in all participants or that the two approaches have identical safety profiles. The safety at-risk counts are not the same as the primary outcome counts in the first group, and the registry record does not explain the accounting. It does not provide event terms, definitions, collection procedures, severity details beyond the serious-event classification, or follow-up completeness. No serious-event terms are listed. The small number of participants with safety data limits what can be inferred about uncommon events.

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

The posted primary results describe average opioid consumption for two randomized groups receiving blocks at different locations. The mean was 23.21 milligrams of morphine equivalents in the true adductor canal group and 18.93 milligrams in the proximal group. The estimated mean difference, proximal compared with true adductor canal, was -4.28 milligrams. This is the direction and magnitude of the observed contrast, not a demonstrated causal effect on its own.

The confidence interval, from -10.76 to 2.195 milligrams, includes zero and leaves uncertainty about both the direction and size of the difference. The unadjusted p-value of 0.195 likewise does not provide strong evidence against the no-difference null model under the reported comparison. Neither result proves that the groups are equal. A finding of no statistically clear difference is not the same as evidence of equivalence, and the registry record does not report an equivalence margin or a noninferiority analysis.

The endpoint measures opioid administration in morphine equivalents, not pain relief, mobility, surgical recovery, or long-term function. The record’s description combines an intraoperative label with a 24-hour timeframe, and does not explain the measurement details or conversion method. Consequently, the results should be kept within the scope of the registered outcome.

The trial record also leaves important interpretive details unreported. The primary outcome group counts total less than the overall enrollment, but the record does not explain why. It does not describe the analysis population, missing-data handling, or adjustment strategy. The single-blind label does not identify who was masked. These limitations do not erase the reported summaries, but they constrain conclusions about precision, generalizability, and the potential influence of analysis choices.

The result therefore supports a cautious statistical reading: the observed group means differ, but the estimated contrast is uncertain and the registry result does not establish a reliable directional difference, equivalence, or a clinical consequence.

16. Why This Trial Matters Statistically

This trial poses a focused statistical comparison: whether opioid consumption differs between two block locations when the listed anesthetic, concentration, and volume are the same. The randomized parallel-group design is relevant because random assignment is intended to reduce systematic differences between groups. The comparison is also expressed in the outcome’s original unit, milligrams of morphine equivalents, which makes the mean difference directly interpretable as a contrast in average recorded consumption.

The trial is statistically informative not only for its point estimate but also for the uncertainty around that estimate. The mean difference is -4.28 milligrams, but its confidence interval ranges from -10.76 to 2.195 milligrams. That interval makes clear why a single group contrast cannot be read as a precise answer: values compatible with the data include no difference and differences in either direction. The p-value of 0.195 is consistent with that uncertainty, but it cannot answer whether the approaches are equivalent or whether any possible difference would matter clinically.

The comparison also illustrates how sample size and outcome variability shape precision. The primary summaries include 21 and 23 participants, and the standard deviations are 12.23 and 9.34 milligrams. Those details help readers understand why the estimate may remain uncertain, while the overall enrollment of 69 raises questions about how the outcome counts were determined. The registry record does not provide the accounting needed to resolve that question.

Finally, the record highlights the value of transparent reporting. Information about masking, analysis populations, missing data, multiplicity, and original sample-size assumptions would help readers evaluate how the analysis was planned and how broadly the results can be interpreted. Without those details, the statistical conclusion should remain anchored to the posted unadjusted summaries and their uncertainty.

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.

Several trial-specific limitations affect interpretation. The registry record lists enrollment of 69, but the primary outcome summaries include 21 participants in the true adductor canal group and 23 in the proximal group. The reason for the difference is not reported in the registry record. Without a participant flow account, it is not possible to determine how many participants contributed outcome data, why the counts differ, or whether the included groups reflect a particular analysis population.

The study is labeled single-blind, but the identity of the masked parties is not reported. The record also does not describe random sequence generation or allocation concealment. These omissions limit evaluation of how treatment assignment was implemented and how expectations might have influenced outcome measurement or care.

The primary endpoint wording identifies opioid consumption as intraoperative and gives a 24-hour timeframe, without clarifying the relationship between those descriptions. The record does not report the opioid conversion procedure, collection method, or detailed analysis plan. It also does not report baseline characteristics, adjusted results, distributional checks, or the original sample-size justification. The planning illustrations use the observed effect and cannot substitute for those original design details.

The safety record reports no serious events or deaths in the listed groups, but the numbers at risk are limited and event-collection details are not given. The motor-block secondary outcome is listed, but its results are not reported in the registry record. Together, these gaps limit assessment of outcome completeness, safety, and the breadth of conclusions that can be drawn from the primary result.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Optimal Location of Nerve Block to Minimize Perioperative Opioid Administration in ACL Surgery: Comparing True Adductor Canal to Proximal Block — NCT03401450.
• Registry record last updated 2023-07-14; status last verified 2023-06.
• Results first posted 2020-12-23.
• 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

NCT03401450 is a completed randomized, single-blind, parallel-group phase 4 trial sponsored by NYU Langone Health. It compared an ultrasound-guided block within the true adductor canal with a proximal femoral triangle block in ACL surgery. Both groups were described as receiving a single injection of 20 mL of 0.5% bupivacaine. Overall enrollment was 69.

The primary outcome was total opioid consumption in milligrams of morphine equivalents, described as intraoperative and measured over a 24-hour timeframe. The reported means were 23.21 milligrams for the true adductor canal group and 18.93 milligrams for the proximal group. The estimated mean difference was -4.28 milligrams, with a 95% confidence interval from -10.76 to 2.195 and an unadjusted p-value of 0.195. The interval includes zero, so the size and direction of the difference remain uncertain.

The record lists motor block as a secondary outcome and reports zero serious adverse events and zero deaths in each listed safety group. Details about the analysis population, missing data, masking roles, and original sample-size assumptions are not reported in the registry record.