Adductor Canal Catheter Effectiveness and Safety Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Adductor Canal Catheter Effectiveness and Safety Study (NCT04639128), a randomized na study. The primary outcome is Pain Numerical Rating Scale.

2. Clinical Question

The registry identifies pain on the second postoperative day as the primary objective. It also describes secondary objectives concerning pain over the postoperative period, opioid consumption, catheter-placement complications, and exploratory predictors of differing response. The posted secondary outcome is opioid consumption during the 15-day postoperative period. No analyses of the exploratory predictor objective are reported in the registry record.

The official title calls the study a noninferiority trial, but the registry record does not report a noninferiority margin or a formal noninferiority analysis. The posted comparison therefore needs to be read as an estimate of the difference in mean day-2 pain scores, with its uncertainty, rather than as a documented formal test of noninferiority.

3. Trial Design

This was a randomized, open-label, parallel-group clinical trial of the adductor canal catheter for pain control after total knee arthroplasty. The registry lists the study as completed and reports enrollment of 126. It names Kaiser Permanente as the sponsor. The study dates recorded are 2021-03-15 for the start and 2022-12-14 for primary completion.

Participants were assigned to usual care with placement of an adductor canal catheter or to usual care without catheter placement. The registry reports no masking. That means the study was not blinded according to the record; it does not, by itself, establish how knowledge of assignment may have influenced participants, clinicians, or outcome reporting.

The primary outcome was a pain numerical rating scale score on the second postoperative day. The arm-level posted results include 60 participants in the No-Device arm and 62 in the Device arm. The registry defines the primary-outcome population as participants who had surgery and could provide a day-2 pain score. The record does not report further details about randomization procedures, allocation concealment, protocol deviations, or the handling of participants who did not contribute a primary score.

The study title describes a noninferiority trial, but the registry record does not report the planned noninferiority margin, the original sample-size justification, or the statistical analysis plan. The sample-size illustrations associated with the posted results are based on the observed effect and are not the trial's own design assumptions. These distinctions matter: the randomized parallel design describes how groups were formed, while the estimand, analysis population, and criteria for a formal noninferiority conclusion depend on details that 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Had surgery and able to provide postoperative day-2 pain score

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 Pain Numerical Rating Scale, measured over Second postoperative day.

The primary endpoint is pain severity on the second postoperative day, measured using an ordinal 0-to-10 pain numerical rating scale. The registry states that 0 is the minimum, 10 is the maximum, and higher scores mean more pain. The reported arm summaries and between-arm comparison treat this outcome as a continuous measure and report means with standard errors.

A numerical rating scale converts a participant's report of pain intensity into a value that can be summarized and compared between randomized groups. For this trial, the second postoperative day is the specified time point for the primary comparison. Selecting a defined time point helps focus the main question and avoids treating every measurement time as equally primary. The registry does not report a broader repeated-measures analysis of pain over time as the primary analysis.

There is a general statistical consideration when an ordinal scale is summarized by a mean: the mean describes the average recorded score, but it does not show the full distribution of individual responses. Two groups can have similar means while differing in how scores are spread or concentrated. The posted means therefore answer a particular question about average scores; they do not describe every participant's experience or the shape of the score distribution.

The outcome is clinically interpretable as a pain score, but the registry record does not report a threshold for a clinically important difference. Consequently, the mean difference and its confidence interval describe the estimated size and precision of the group contrast, while the record does not supply a threshold for deciding whether a particular difference would be important to patients.

7. Results Posted in the Registry

• Device: mean 5.31 versus 6.38 on control; difference -1.07 (95% CI -1.93 to -0.21), standardized effect d = -0.44; z-test p = 0.015.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Opioid Consumption in the 15-day Postoperative Period

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Device: mean 46.00 versus 41.90 on control; difference 4.10 (95% CI -9.60 to 17.80), standardized effect d = 0.12; z-test p = 0.558.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Device and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists opioid consumption over the 15 postoperative days as the posted secondary outcome. Its estimate is less precise than the primary comparison: the confidence interval covers values in either direction, and the unadjusted p-value does not indicate a clear separation of the group means under the posted analysis. This pattern does not establish that consumption was the same between groups; the data remain compatible with a range of differences.

The secondary outcome relates to the primary question by adding a measure of postoperative medication use alongside day-2 pain scores. These outcomes address different aspects of the postoperative period, and a pattern in one does not determine the result in the other. The registry's brief summary also describes broader secondary objectives involving overall pain, catheter-related complications, and exploratory predictors. However, those objectives are not accompanied by posted analyses in the registry record. Only one secondary outcome is posted, and no analyses are listed.

Unadjusted secondary results generally carry less weight than a prespecified primary result when several outcomes or analyses are considered. General statistical explanation: examining multiple outcomes creates more opportunities for apparently notable findings to arise by chance, unless the analysis plan accounts for that multiplicity. The registry record does not report a multiplicity adjustment, a testing hierarchy, or the full analysis plan. This makes it difficult to know how the secondary result was positioned in the original inferential plan.

The secondary estimate should therefore be treated as supporting descriptive evidence, not as a substitute for the primary endpoint or as a standalone basis for a broad conclusion. Its interpretation is also limited by the smaller number of participants with posted results than for the primary endpoint. The registry record does not explain why those counts differ, whether any data were missing, or how missing observations were handled.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Opioid Consumption in the 15-day Postoperative Period

9. Statistical Interpretation

10. Statistical Methods Explained

The posted primary outcome is continuous in the analysis: each participant contributes a pain score, and the group results are presented as means with standard errors. A mean summarizes the average score in a group. A standard error describes the estimated sampling variability of that mean; it is not the spread of individual scores. General statistical explanation: a standard error tends to be smaller when a group mean is estimated more precisely, but it does not reveal whether individual responses are tightly clustered or widely dispersed.

What does the mean difference represent?

The reported comparison is the mean score in the Device arm minus the mean score in the No-Device arm. The estimate is -1.07, based on posted means of 5.31 and 6.38, respectively. A negative value means the Device-arm mean is lower on the scale in this comparison. This is an unadjusted contrast of group summaries; the registry does not report an adjusted model for the primary outcome.

The registry also posts a confidence interval for the primary mean difference. A confidence interval is a range of values compatible with the estimate and the assumptions of the statistical procedure. General statistical explanation: it conveys uncertainty more directly than a single estimate, but it is not a range containing a known fraction of individual participant scores. The posted primary interval lies entirely below zero. The record does not report the confidence level explicitly in the outcome description, so the interval should be read as posted rather than assigned a confidence level that is not stated there.

How should the p-value be read?

The unadjusted p-value for the primary comparison is 0.015. In general, a p-value measures how incompatible the observed data are with a specified statistical null model, if that model and its assumptions hold. It is not the probability that the null hypothesis is true, and it does not quantify the size or importance of the group difference. The registry labels this result as unadjusted; it does not report whether the p-value was part of a prespecified testing hierarchy or adjusted for other outcomes.

The outcome is described as an ordinal scale, while the posted analysis reports a mean difference. General statistical explanation: treating ordinal scores through means can be useful for summarizing average scores, but it imposes a particular summary on ordered categories. Means do not show the full distribution, and the registry does not post distributional summaries or a separate ordinal-model analysis. The available comparison should therefore be interpreted as a contrast in average recorded score, not as a complete description of the ordinal response pattern.

What does the noninferiority label require?

General statistical explanation: a noninferiority analysis tests whether an intervention's outcome is not worse than a comparator by more than a prespecified acceptable margin. That margin must be defined before interpreting the result, and the confidence interval must be evaluated relative to it. The registry title uses the term noninferiority, but the margin and the formal analysis are not reported in the registry record. The posted mean difference and unadjusted p-value cannot substitute for those missing elements. The registry record also does not report the trial's original sample-size justification or its prespecified statistical analysis plan.

How do the secondary results fit the same framework?

Opioid consumption is reported as a continuous outcome in units of 5mg oxycodone tablets over 15 postoperative days. The arm means are 41.9 and 46.0, and the posted mean difference is 4.1 for Device minus No-Device. Its confidence interval extends from -9.604 to 17.8, and its unadjusted p-value is 0.558. The interval includes zero, indicating that the estimate is not precise enough to exclude differences in either direction under the posted comparison. This is not evidence of equivalence, and it should not be interpreted as proving that the groups have identical opioid consumption.

General statistical explanation: a wide confidence interval can arise when the data leave substantial uncertainty about the effect size. Here, the endpoint has 47 participants in the No-Device arm and 46 in the Device arm, compared with 60 and 62 for the primary endpoint. The registry record does not explain the difference in participant counts, so no reason for it should be assumed. The standard errors reported for the secondary means describe uncertainty in those means, not the variability among individual opioid-consumption values.

The comparison results are simple unadjusted re-calculations from posted summary statistics. The registry reports no analysis entries for the posted outcome results. The discrepancy indicator is false, so the posted comparison estimates can be read without a flagged disagreement between a sponsor analysis and a re-calculation. More generally, when a discrepancy is flagged, the sponsor's own analysis takes precedence. No such discrepancy is flagged for this record.

11. Confidence Intervals and Precision

The primary mean difference is -1.07, with a posted confidence interval from -1.93 to -0.210. Both bounds are below zero, so the interval is consistent with a lower average day-2 pain score in the Device arm under the posted contrast. The interval still spans a range of possible effect sizes; it does not make the estimate exact. The registry does not report a threshold for a clinically important difference, so statistical precision cannot by itself determine whether the range is clinically meaningful.

The confidence interval is more informative than the point estimate alone because it displays uncertainty around the estimated mean difference. General statistical explanation: narrower intervals indicate more precision, while wider intervals leave more plausible values compatible with the data and analysis. An interval does not describe where most individual scores fall, and it does not guarantee that the true effect lies within its endpoints. Its interpretation depends on the statistical model and the analysis population.

For opioid consumption, the posted confidence interval runs from -9.604 to 17.8 around the mean difference of 4.1. Because that range includes zero and extends in both directions, the secondary estimate is compatible with different directions of group difference. The unadjusted p-value is 0.558. These results indicate uncertainty rather than proof that no difference exists. The endpoint has fewer participants contributing than the primary pain outcome, and the registry record does not state why.

The primary confidence interval is distinct from the noninferiority question. A formal noninferiority interpretation requires comparing the interval with a prespecified margin; that margin is not reported in the registry record. Accordingly, the interval supports interpretation of the estimated average contrast and its precision, but cannot establish a formal noninferiority conclusion on its own.

12. 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 event counts. They 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 a stated fraction of the observed effect. The registry record does not report the trial's own original design assumptions or sample-size justification; these are planning illustrations based on the observed result, not a reconstruction of the trial's design.

The 80% power column describes the planned number of participants per arm under the stated assumptions to give an 80% chance of detecting the chosen effect if that effect and the assumptions hold. The 90% power column gives the corresponding planning number for a 90% chance. These are prospective planning concepts: higher target power generally requires more participants when other assumptions remain fixed. In each planning scenario, the figures increase as the assumed effect becomes smaller, because smaller differences are harder to distinguish from sampling variability.

The rows use 100%, 75%, and 50% of the observed effect as planning targets. The figures are not observed power, and they do not describe the probability that the completed trial's finding is true. They also do not establish that the original trial was designed around any of these effects. The calculations are illustrations based on the posted estimate and the assumptions stated in the registry record. A sample-size curve based on these assumptions should be read as showing how the planning requirement changes with the target effect, rather than as a report of the number enrolled or a result of the trial.

13. 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 = -1.070; pooled standard deviation σ = 2.425.
2. n = 2 × (1.96 + 0.842)² × 2.425² / -1.070² = 80.7, rounded up to 81 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 <- -1.07                      # observed difference in means
sigma <- 2.42534671060998                     # 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(4639128)
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 = 81 (80% power), 108 (90% power)
 75% of observed effect: n per arm = 144 (80% power), 192 (90% power)
 50% of observed effect: n per arm = 323 (80% power), 432 (90% power)
power.t.test: 81.6 
Simulated power at n = 81 per arm: 0.794 (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.

14. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity adjustment, a prespecified testing hierarchy, or the statistical analysis plan. It lists one posted secondary outcome and no reported analyses. The brief summary describes additional secondary and exploratory objectives, but the record does not provide analyses for them. Without a plan specifying which comparisons were primary, how other tests were to be handled, and how inference would be controlled across them, the role of the unadjusted secondary result is uncertain.

General statistical explanation: when investigators test multiple outcomes or conduct many exploratory analyses, the chance of at least one apparently unusual result can increase. Methods such as hierarchical testing or adjusted significance thresholds can address that issue, but the registry record does not say whether any such methods were planned or used. The primary comparison's unadjusted p-value should not be treated as adjusted for all objectives in the brief summary.

The primary outcome population is defined as participants who had surgery and were able to provide a postoperative day-2 pain score. The registry reports 60 participants for the No-Device primary result and 62 for the Device result. For opioid consumption, it reports 47 and 46 participants, respectively. These differing endpoint counts are visible in the posted results, but the reason for the differences is not reported in the registry record.

The record does not describe how missing outcomes were handled, whether any imputation was performed, whether analyses followed intention-to-treat or per-protocol principles, or how protocol deviations were treated. It also does not report a complete analysis population definition beyond the primary endpoint eligibility description. These omissions matter because missingness and analysis-population choices can affect estimates, particularly in a noninferiority study. No inference about the cause or impact of missing data can be made from the participant counts alone.

15. 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 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: vertigo (1.6%), small-bowel obstruction (1.6%), atrial fibrillation (1.6%), wound dehiscence (1.6%).

The registry reports serious adverse event counts for groups with 63 participants at risk each. There were 3 serious adverse events in the No-Device group and 1 in the Device group. The record reports no deaths in either group. It reports 0 other adverse events in each group among 63 participants at risk.

These counts describe the events recorded in the registry; they do not by themselves establish whether an event was caused by the catheter or by the surgery. The registry lists vertigo, small-bowel obstruction, atrial fibrillation, and wound dehiscence among the leading serious-event terms, each at 1.6%. The record does not assign those listed terms to a specific group in the information, so they should not be attributed to either arm.

General statistical explanation: adverse-event counts are descriptive safety information. A small count may provide limited precision about how often an event occurs, and comparisons of counts do not by themselves establish causality. The registry's brief summary identifies complications related to catheter placement as an objective, but the posted serious-event figures do not provide a causal assessment for each event. The record does not report additional detail on event timing, severity beyond the serious classification, or attribution.

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

The posted primary result shows a lower mean day-2 pain score in the Device arm than in the No-Device arm, with a mean difference of -1.07 and a confidence interval that lies below zero. This is evidence about the average score in the recorded primary-outcome population, using the comparison posted in the registry. It does not describe every participant's pain, establish how individual responses were distributed, or quantify a clinically important difference because no such threshold is reported.

The trial's official title describes a noninferiority study, but the registry record does not report the margin or a formal noninferiority analysis. The day-2 estimate should therefore not be presented as proof of noninferiority. A formal conclusion depends on prespecified criteria that are absent from the registry record. The same caution applies to claims about the original design: the posted planning illustrations are not the trial's original sample-size justification.

The secondary opioid-consumption result has substantial uncertainty and does not establish either equality or a definite difference between groups. It adds a separate outcome to the interpretation but should not override the primary endpoint. The record also provides serious adverse-event counts and leading event terms, without establishing causation or reporting a complete catheter-related safety analysis.

The randomized design supports a group comparison, while the open-label nature and unreported details of allocation, analysis populations, missing-data handling, and multiplicity limit what can be assessed from the registry record. The endpoint counts differ, and their explanation is not reported. Together, these details mean the posted statistics can be read as estimates for the recorded outcomes and populations, but broader claims about all objectives, individual benefit, formal noninferiority, or causal safety attribution are not established by the information in the registry record.

17. Why This Trial Matters Statistically

This study illustrates why the label attached to a trial and the analysis needed to support that label are not the same thing. The official title describes a noninferiority trial, yet the registry record does not report the noninferiority margin or the formal analysis. A mean difference and confidence interval are useful for understanding the observed contrast, but a noninferiority claim requires an explicit margin and a decision rule tied to it.

It also highlights the importance of distinguishing statistical evidence from clinical importance. The posted primary estimate is precise enough for its interval to remain below zero, but the registry does not state what size of pain-score difference would be clinically important. Statistical location relative to zero cannot answer that separate question.

The endpoint counts, analysis populations, and secondary results also show why registry reporting details matter. The primary and secondary outcomes have different numbers of contributing participants, while the reasons and missing-data procedures are not reported. The record lists broad secondary objectives, but only one secondary outcome is posted and no analyses are listed. Readers therefore need to distinguish reported results from objectives that have no posted analysis.

Finally, the sample-size illustrations demonstrate how planning assumptions shape required enrollment: smaller target effects require more participants under the stated approach. Because these illustrations use the observed effect rather than the original design rationale, they cannot explain why the trial enrolled the number it did. Keeping these statistical distinctions visible prevents an estimate, a planning scenario, a trial label, and a formal conclusion from being treated as interchangeable.

18. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record does not report the noninferiority margin or the formal analysis required to assess the noninferiority claim in the official title. It also does not report the original sample-size justification or a complete statistical analysis plan. These omissions limit evaluation of whether the primary comparison followed the intended inferential framework.

The trial was open-label, with no masking reported. The record does not describe how knowledge of assignment was managed or whether outcome assessment could be influenced by that knowledge. The primary endpoint is a participant-reported pain score, and the registry does not post the score distribution or an ordinal-model analysis in addition to the mean summaries.

The numbers contributing to the posted primary and secondary outcomes differ. The registry record does not explain these differences or describe missing-data handling, imputation, or intention-to-treat and per-protocol analyses. The primary population definition includes participants who had surgery and could provide a day-2 pain score, but further analysis-population details are not reported.

The registry also does not report a multiplicity strategy despite describing multiple secondary and exploratory objectives. Only one secondary outcome is posted, and no analyses are listed. For safety, the record provides serious-event counts and leading terms, but does not report event attribution or a detailed analysis of catheter-related complications. These limitations do not erase the posted estimates; they define the boundaries of what can be inferred from the registry record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Adductor Canal Catheter Effectiveness and Safety Study — NCT04639128.
• Registry record last updated 2024-04-25; status last verified 2024-04.
• Results first posted 2024-04-25.
• 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.

22. Record Summary

NCT04639128, Adductor Canal Catheter Effectiveness and Safety Study, is recorded as a completed randomized, open-label, parallel-group trial sponsored by Kaiser Permanente. The registry reports enrollment of 126 and compares usual care with an adductor canal catheter against usual care without one after total knee arthroplasty.

The primary outcome is a day-2 pain numerical rating scale score. The posted comparison reports a lower mean in the Device arm, with a mean difference of -1.07 and an interval below zero. The registry also posts opioid consumption over the 15 postoperative days; that comparison is less precise and does not establish equality or a definite difference.

The title identifies the study as noninferiority, but the margin and formal analysis are not reported in the registry record. The record also does not report the original sample-size justification, multiplicity procedures, or missing-data methods. Serious adverse event counts are posted for both groups, with no deaths reported.