Efficacy of Ipack Block and Surgeon's Joint Infiltration in Total Knee Arthroplasty: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy of Ipack Block and Surgeon's Joint Infiltration in Total Knee Arthroplasty (NCT03653416), a randomized phase 4 study. The primary outcome is Narcotic Consumption.

2. Clinical Question

The clinical contrast is between adding an Ipack block to the described periarticular care and receiving the described periarticular care without that block. The endpoint concerns narcotic consumption, not pain scores alone. Pain scores, time to first narcotic dose, post-anesthesia care unit length of stay, pain location, ambulation distance, and the Bartels Index are listed as secondary outcomes. Their names indicate additional aspects of recovery that were of interest, but results for them are not reported in the registry record.

The registry describes the study as a randomized controlled trial. Random assignment is intended, in general, to make the compared groups similar on average at the start of a study, though it does not guarantee balance in every characteristic. The record does not report baseline characteristics or details of the randomization procedure, so the quality of balance and implementation cannot be assessed from the reported information.

3. Trial Design

The registry identifies this study as a completed, randomized, quadruple-masked, parallel-group Phase 4 trial. It lists the sponsor as Icahn School of Medicine at Mount Sinai. The recorded study start is 2018-03-01, and the primary completion date is 2019-08-01. Enrollment is recorded as 99. The registry record does not explain the masking procedures or identify which roles were masked, so the meaning of quadruple masking cannot be made more specific from this record.

The parallel design compares participants assigned to the Ipack group with participants assigned to the periarticular group. The Ipack arm description specifies an ultrasound-guided injection of 20 cc of bupivacaine at 0.25%, as well as an adductor canal catheter and periarticular infiltration. The periarticular group description specifies an adductor canal catheter and periarticular infiltration. The registry lists Ipack as a device, bupivacaine as a drug, and periarticular infiltration as a procedure.

The primary endpoint is narcotic consumption during the first 24 hours, reported as a mean in morphine equivalents, mg, with standard deviations. The posted summaries list 46 participants for each arm. The relationship between these arm-level counts and the recorded enrollment of 99 is not reported in the registry record. Reasons for any difference, participant flow, and the analysis population are also not reported.

The record names six secondary outcomes: pain measured by Visual Analogue Score, time to first narcotic dose, post-anesthesia care unit length of stay, pain by location, ambulation distance, and Bartels Index. Although these outcomes are listed, their results are not reported in the registry record. The record does not report the trial’s original sample-size rationale, detailed statistical analysis plan, or interim-analysis procedures.

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 Narcotic Consumption, measured over 24 hours.

The primary endpoint is narcotic consumption in the first 24 hours, expressed in morphine equivalents, mg. The registry describes the measure as a mean and gives a standard deviation for each group. In general, expressing narcotic use in morphine equivalents places different narcotic medications on a common scale, though the conversion procedures used in this trial are not reported in the registry record.

This measure captures medication use over a defined period after surgery. In general, consumption can complement patient-reported pain scores: a pain score describes a person’s reported experience at an assessment, while consumption records medication used over a period. Neither measure alone fully describes recovery or the reasons a medication was or was not taken. For example, prescribing practices, timing of assessments, and individual preferences can influence medication use; trial-specific details about such factors are not reported in the registry record.

The endpoint is clinically interpretable as a group average, but the mean does not describe how consumption varied among individuals. The posted standard deviations are relatively large compared with the group means, indicating substantial spread in the reported measurements. The endpoint also does not by itself establish whether any difference would be meaningful to patients. A threshold for a clinically important difference is not reported in the registry record.

The assessment period is restricted to the first 24 hours. The result therefore addresses consumption over that interval, not later use, pain after discharge, or other dimensions of recovery. Those broader outcomes cannot be inferred from this primary measure.

7. Results Posted in the Registry

• Pai (Peri Articular) Group: mean 13.67 versus 15.87 on control; difference -2.20 (95% CI -10.20 to 5.80), standardized effect d = -0.11; z-test p = 0.590.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: narcotic consumption is measured on a numerical scale, and the registry reports a mean and standard deviation for each arm. For a continuous endpoint, a difference in group means provides a direct summary of the contrast in average outcomes. It does not imply that every participant in one group had lower consumption than every participant in the other group.

What does the mean difference represent?

The registry reports a mean of 15.87 mg for the Ipack group and 13.67 mg for the periarticular group. The comparison estimate is -2.2 mg for the periarticular group relative to the Ipack group. This direction follows the comparison as recorded: a negative estimate means the periarticular group’s posted mean is lower. The estimate is a point estimate, meaning it is the single best value from the reported calculation, not a statement that the true difference is known exactly.

In general, a mean is sensitive to all observations and can be influenced by unusually high or low values. The registry’s standard deviations—19.75 mg and 19.39 mg—describe the spread of observations around their respective means. They are not standard errors and do not directly provide the uncertainty of the difference. The reported confidence interval is the more direct summary of uncertainty for the comparison.

How should the confidence interval be read?

A confidence interval gives a range of values compatible with the data and the method used to calculate it. In repeated applications of a suitable procedure, intervals constructed in this way would cover the underlying quantity at the stated confidence level. The registry record does not state the confidence level, so it should not be inferred from the interval alone. The reported interval runs from -10.2 to 5.798 mg. Because it spans zero, it includes the possibility of no difference and also values in either direction.

The interval is about uncertainty in the average contrast. It is not a prediction interval for individual participants, and it does not mean that all individual effects lie within its limits. A wide interval can arise when measurements are variable or the amount of information is limited. Here, the standard deviations indicate considerable variation, while the arm-level counts and the interval provide context for the precision of the group comparison.

What does the unadjusted p-value say?

The registry reports an unadjusted p-value of 0.59. In general, a p-value describes how unusual data at least as inconsistent with a specified null model would be if that model and the statistical assumptions were correct. It is not the probability that the null hypothesis is true, and it does not measure the probability that the result occurred “by chance.” A large p-value does not establish equivalence or demonstrate that there is no meaningful difference.

The record labels the p-value unadjusted. It does not report whether other comparisons were accounted for in a multiplicity procedure. The estimate and interval remain important alongside the p-value: together they indicate the direction of the observed contrast and the range of values that the analysis does not rule out.

Why can variability matter?

In general, over-dispersion means that outcome variation is greater than a model expects. This can make model-based uncertainty estimates too small if the extra variation is ignored. The endpoint is analyzed as a continuous measure, and the registry reports standard deviations, but it does not describe a model, distributional checks, or an over-dispersion assessment. No claim about whether a particular model assumption was met can be made from the registry record.

The comparison lists a pooled standard deviation of 19.57 mg, but the registry does not describe the statistical procedure used to form the primary estimate, confidence interval, or p-value. It also does not report covariate adjustment. The reported comparison should therefore be understood as the posted result, without assuming details of a model or adjustment strategy that are not stated.

10. Confidence Intervals and Precision

The registry reports a mean-difference estimate of -2.2 mg, with a confidence interval from -10.2 to 5.798 mg. This interval is wide enough to include a range of possible contrasts, including zero. It also extends into values in both directions. The observed estimate therefore has limited precision as a guide to the exact size and direction of the underlying mean difference.

Precision concerns how narrowly the data locate an estimate. It is distinct from whether an estimate is clinically important. A narrow interval can still center on a small or unimportant effect, while a broad interval can include effects that might matter in either direction. The registry does not state a threshold for a clinically important difference in narcotic consumption, so the interval cannot be judged against a trial-specific clinical benchmark.

The standard deviations are 19.75 mg for the Ipack group and 19.39 mg for the periarticular group, compared with posted means of 15.87 mg and 13.67 mg. This spread indicates substantial variation in participant-level consumption relative to the group averages. The interval for the difference, rather than the standard deviations alone, is the relevant summary for precision of the mean contrast.

The confidence level and calculation method are not reported in the registry record. The confidence interval should therefore be read as the interval posted in the registry, without attributing an unreported confidence level or model to it. Its inclusion of zero is consistent with the unadjusted p-value of 0.59; neither statistic demonstrates equivalence or proves that there is no 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 planning figures are participants per arm, not total events. They are illustrations based on fractions of the observed effect, rather than the trial’s original design calculation. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is defined as the stated fraction of the observed effect: 100%, 75%, or 50%.

The 80% power column gives the number of participants per arm that the planning calculation estimates would be needed to have an 80% chance of detecting the specified effect under those assumptions, if that effect were the true one. The 90% power column gives the corresponding planning figure for a 90% chance. These are prospective planning quantities, not descriptions of the precision or power achieved in this completed trial. They are not observed power.

The figures increase as the target effect becomes smaller. This is the usual relationship: a smaller difference is harder to distinguish from random variation, so more participants are generally needed to detect it at the same significance level and power. The observed effect used for these illustrations is small relative to the reported variability, so the resulting participant requirements are large. The calculation is a planning aid rather than a recommendation for a future study.

The registry record does not report the trial’s own original sample-size assumptions or justification. The planning figures should not be treated as evidence that the completed trial was designed around those assumptions, nor as a substitute for a design calculation using a prespecified clinically important effect and an appropriate analysis plan.

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 = -2.200; pooled standard deviation σ = 19.571.
2. n = 2 × (1.96 + 0.842)² × 19.571² / -2.200² = 1,242.3, rounded up to 1,243 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 <- -2.2                      # observed difference in means
sigma <- 19.5708277801426                     # 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(3653416)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 1,243 (80% power), 1,664 (90% power)
 75% of observed effect: n per arm = 2,209 (80% power), 2,957 (90% power)
 50% of observed effect: n per arm = 4,970 (80% power), 6,653 (90% power)
power.t.test: 1243.2 
Simulated power at n = 1,243 per arm: 0.801 (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 six secondary outcomes: Visual Analogue Score for Pain, time to first dose of narcotic administration, post-anesthesia care unit length of stay, number of participants with pain by location, ambulation distance, and Bartels Index. Their results are not reported in the registry record. The primary comparison has an unadjusted p-value of 0.59, but the record does not state whether a multiplicity adjustment was planned or applied across the primary and secondary outcomes.

In general, making many statistical comparisons increases the chance that at least one result may appear noteworthy even when no underlying effect exists. Multiplicity procedures can control that risk, but they may also affect the interpretation and precision of individual comparisons. Since the registry does not describe a correction strategy or a hierarchy of outcomes, no claim can be made about how multiplicity was handled.

Missing-data methods and analysis populations are also not reported in the registry record. The primary summaries list 46 participants in each group, while enrollment is recorded as 99. The record does not explain the difference, state whether all randomized participants contributed to the endpoint, or describe exclusions, withdrawals, or missing outcome values. It does not specify whether the analysis followed randomized assignment or used another population definition.

In general, missing observations can affect estimates if the likelihood of missingness is related to outcome values or group assignment. Statistical methods such as imputation or sensitivity analysis may address some missing-data concerns, but the registry record does not report whether any such methods were used. Without participant flow and analysis details, the extent and potential influence of missing data cannot be assessed.

The record also does not report a detailed statistical analysis plan, covariate adjustment, or interim analyses. These details should not be inferred from the posted summary statistics. The primary result can be described as recorded, while conclusions about prespecification, multiplicity control, and analysis-population choices remain unavailable.

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 5% reporting threshold.

For the Ipack group, the registry reports 46 participants at risk for serious adverse events and 0 affected; it also reports 46 at risk for other adverse events and 0 affected. For the periarticular group, the corresponding figures are 46 at risk and 0 affected for serious adverse events, and 46 at risk and 0 affected for other adverse events. Deaths are reported as 0 in each group. No serious adverse-event terms are listed.

These figures describe events recorded in the registry, not proof that no adverse events occurred outside the reported categories or observation procedures. The record does not provide definitions, follow-up duration for safety, event-ascertainment procedures, or detailed event narratives. It also does not report whether participants had incomplete safety follow-up.

Zero reported events in these groups means that the registry records no affected participants for the listed serious and other adverse-event summaries. It does not establish that the interventions have no risks. The safety information should be interpreted as limited registry reporting, alongside the absence of detail about surveillance and follow-up.

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

The posted primary result describes average narcotic consumption during the first 24 hours after total knee arthroplasty. The observed mean was 15.87 morphine-equivalent mg in the Ipack group and 13.67 mg in the periarticular group. The registry’s estimated mean difference, periarticular relative to Ipack, is -2.2 mg. The confidence interval ranges from -10.2 to 5.798 mg and includes zero; the unadjusted p-value is 0.59.

These findings do not establish that the groups are equivalent. A result that does not provide strong evidence against no difference is not the same as evidence that any difference is absent or sufficiently small. The interval permits a range of possible contrasts, and the registry record does not provide a prespecified equivalence margin or a clinically important difference threshold.

The result also does not establish whether a difference is important to patients. Narcotic consumption is one measure over a limited period. The registry lists pain scores and other recovery outcomes, but does not report their results. The primary endpoint alone cannot describe later recovery, pain experience, mobility, or the overall balance of outcomes.

The registry reports no participants affected by serious or other adverse events in either group and no deaths. Those recorded counts are reassuring only in the narrow sense that no events appear in these summaries; they do not establish absence of risk, particularly because safety follow-up and ascertainment details are not reported.

Interpretation is further limited by the absence of reported participant flow, missing-data handling, analysis-population definitions, and a detailed statistical plan. The record gives enrollment of 99, while the primary outcome summaries list 46 participants per arm, without explaining the relationship. The appropriate conclusion is therefore limited to the posted estimates and their uncertainty: the registry reports a modest negative point estimate for periarticular relative to Ipack consumption, but the interval is compatible with effects in either direction and does not settle the clinical question.

16. Why This Trial Matters Statistically

This trial raises a useful statistical question about how to interpret a group-average difference when individual outcomes vary substantially. The primary endpoint is continuous, and the reported standard deviations are larger than the group means. In that setting, the point estimate alone can give a misleading impression of certainty. The confidence interval adds essential context by showing that the compatible range includes zero and extends in both directions.

The comparison also illustrates why a non-significant p-value should not be translated into proof of no effect. The unadjusted p-value is 0.59, but the confidence interval still allows differences that may be relevant, depending on a clinical threshold that is not reported. Equivalence requires a prespecified margin and an analysis designed to assess whether uncertainty is contained within that margin; such information is not reported in the registry record.

Another statistical issue is the gap between enrollment and the arm-level outcome counts. Enrollment is recorded as 99, while each primary-outcome summary lists 46 participants. Without participant flow and analysis-population descriptions, readers cannot determine how the endpoint summaries relate to random assignment or whether missing outcomes could affect the result. Transparent reporting of these details is important for assessing the credibility and generalizability of a trial estimate.

The registry’s safety summaries record no adverse events in either group, but do not explain the duration or methods of follow-up. Likewise, secondary outcomes are named without posted results. These reporting limitations show why a trial result should be interpreted as a body of evidence with scope and uncertainty, rather than as a single p-value or a single safety count.

17. Limitations

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

The registry record leaves several trial-specific questions unresolved. It reports enrollment of 99 and primary-outcome summaries based on 46 participants in each arm, but does not explain participant flow or the relationship between these counts. Reasons for exclusions, withdrawals, or missing endpoint data are not reported. The analysis population and handling of missing values are also not reported.

The record identifies the trial as quadruple-masked but does not specify which participants, clinicians, outcome assessors, or analysts were masked, or how masking was maintained. It describes random allocation but does not provide the sequence-generation or allocation-concealment procedures. Baseline characteristics are not included in the reported information, so group comparability cannot be assessed directly.

The primary outcome is reported with group means and standard deviations, but the statistical model and confidence-interval method are not described. The confidence level is not stated. No clinically important difference threshold or equivalence margin is reported. The registry does not describe a multiplicity adjustment, covariate adjustment, interim analyses, or a detailed statistical analysis plan.

The six secondary outcomes are listed without results in the registry record. Safety summaries report zero affected participants in the serious and other adverse-event categories, but event definitions, ascertainment, and safety follow-up are not described. The original sample-size justification is not reported, so the planning illustrations based on the observed effect should not be mistaken for the trial’s design rationale.

These limitations do not change the posted primary estimate, but they constrain how confidently it can be interpreted. They prevent a full assessment of missingness, prespecification, safety surveillance, and the relationship between the analyzed data and randomized participants.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Efficacy of Ipack Block and Surgeon's Joint Infiltration in Total Knee Arthroplasty — NCT03653416.
• Registry record last updated 2020-11-03; status last verified 2020-10.
• Results first posted 2020-11-03.
• 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

The registry record describes a completed, randomized, quadruple-masked, parallel-group Phase 4 trial comparing an Ipack block strategy with periarticular infiltration for total knee arthroplasty. Enrollment is recorded as 99. The primary outcome is mean narcotic consumption in morphine equivalents, mg, during the first 24 hours.

The posted means are 15.87 mg for the Ipack group and 13.67 mg for the periarticular group. The reported mean difference for periarticular relative to Ipack is -2.2 mg, with a confidence interval from -10.2 to 5.798 mg and an unadjusted p-value of 0.59. The interval includes zero and allows effects in either direction.

Six secondary outcomes are listed, but their results are not reported in the registry record. Safety summaries record zero serious and other adverse events and zero deaths in both groups. Participant flow, missing-data methods, analysis-population definitions, and the trial’s original sample-size rationale are not reported.