A Clinical Trial of Two Periarticular Multimodal Drug Injections in Total Hip and Knee Arthroplasty: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Clinical Trial of Two Periarticular Multimodal Drug Injections in Total Hip and Knee Arthroplasty (NCT02543801), a randomized phase 4 study. The primary outcome is Pain Score.

2. Clinical Question

This is a question about differences in group averages and the uncertainty around those differences, not a direct account of how every participant felt. Higher pain scores indicate worse pain on the registry's 0–10 scale. The record describes the study as evaluating two routinely used drug combinations for pain control after arthroplasty. The results can characterize the recorded outcomes in the analyzed groups, but they do not by themselves establish that one regimen is preferable for an individual or for every clinical setting.

3. Trial Design

The registry record describes a prospective, randomized, double-masked, parallel-group phase 4 trial sponsored by Kootenai Health. The trial enrolled 239 participants and is marked completed. It included hip and knee arthroplasty cohorts, with each cohort assigned to one of two periarticular injection combinations. The liposomal-bupivacaine combination included bupivacaine, clonidine, epinephrine, and ketorolac; the ropivacaine combination included clonidine, epinephrine, and ketorolac.

The posted pain results are divided into four arms: Hip Cohort Liposomal Bupivacaine, with 60 participants; Hip Cohort Ropivacaine, with 58; Knee Cohort Liposomal Bupivacaine, with 59; and Knee Cohort Ropivacaine, with 59. These arm counts describe the outcome results. The record does not give further details about allocation procedures, how masking was maintained, or whether all randomized participants were included in each outcome analysis.

The primary outcome was a continuous measure: the mean of participants' self-reported pain scores collected after surgery and at four-hour intervals up to 48 hours. The secondary outcomes were narcotic consumption and length of stay. The record lists the timeframes and descriptive arm results for these outcomes, but reports no sponsor analyses for them. The trial's original sample-size rationale, planned statistical model, and analysis populations are not reported in the registry record. The planning illustrations accompanying the posted summaries are not evidence of the trial's original design assumptions.

The record includes arm-level means and standard deviations, along with unadjusted comparisons calculated from the posted summaries. It does not report a sponsor-authored inferential analysis for the outcomes. The displayed comparisons also use the hip liposomal-bupivacaine arm as the reference for both knee arms. Consequently, the knee comparisons do not isolate the difference between the two treatment combinations within the knee cohort.

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.

Before assignment: Patients would be excluded if surgery was cancelled or for some clinical reason did not receive the periarticular injection during surgery.

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 Pain Score, measured over Starting post operatively and then every four hours up to 48 hours.

The primary endpoint is pain score, recorded on a scale from 0 to 10, where 0 means no pain and 10 means the worst possible pain experienced. Higher scores indicate worse pain. Participants self-reported pain repeatedly after surgery; the registry says scores were collected every four hours according to hospital care standards, beginning postoperatively and continuing up to 48 hours. The scores for each participant were averaged across that period, and the group mean was then calculated.

Averaging repeated ratings gives a single continuous summary of reported pain over the observation period. It can represent the overall level of pain recorded across multiple assessments, rather than relying on one rating at one moment. It also means that variation in pain over time is not described by the single mean alone. The record does not report time-specific pain comparisons, the number of ratings available for each participant, or how missing ratings were handled.

The arm means were 3.78 for the hip liposomal-bupivacaine group, 3.85 for the hip ropivacaine group, 3.3 for the knee liposomal-bupivacaine group, and 3.4 for the knee ropivacaine group. The accompanying standard deviations describe variation among participant-level average scores within each arm. They do not indicate the precision of an individual participant's score, and they are distinct from the uncertainty around a difference between group means.

7. Results Posted in the Registry

• Hip Cohort Ropivacaine: mean 3.85 versus 3.78 on control; difference 0.07 (95% CI -0.69 to 0.83), standardized effect d = 0.03; z-test p = 0.857.
• Knee Cohort Liposomal Bupivacaine: mean 3.30 versus 3.78 on control; difference -0.48 (95% CI -1.24 to 0.28), standardized effect d = -0.23; z-test p = 0.215.
• Knee Cohort Ropivacaine: mean 3.40 versus 3.78 on control; difference -0.38 (95% CI -1.19 to 0.43), standardized effect d = -0.17; z-test p = 0.359.

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.

Narcotic Consumption

• 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 deviations.
• Result:
  • Hip Cohort Ropivacaine: mean 57.40 versus 48.80 on control; difference 8.60 (95% CI 0.53 to 16.67), standardized effect d = 0.38; z-test p = 0.037.
  • Knee Cohort Liposomal Bupivacaine: mean 52.20 versus 48.80 on control; difference 3.40 (95% CI -5.88 to 12.68), standardized effect d = 0.13; z-test p = 0.473.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Hip Cohort Ropivacaine than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Knee Cohort Liposomal Bupivacaine and the control. The interval gives the range of effects that remain compatible with the data.

Length of Stay

• 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 deviations.
• Result:
  • Hip Cohort Ropivacaine: mean 50.30 versus 33.80 on control; difference 16.50 (95% CI -0.94 to 33.94), standardized effect d = 0.34; z-test p = 0.064.
  • Knee Cohort Liposomal Bupivacaine: mean 36.00 versus 33.80 on control; difference 2.20 (95% CI -12.19 to 16.59), standardized effect d = 0.05; z-test p = 0.765.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Hip Cohort Ropivacaine and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Knee Cohort Liposomal Bupivacaine and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes add context about resource use and hospitalization, but they do not resolve the uncertainty in the primary pain comparisons. Narcotic consumption and length of stay are different measures from self-reported pain, and a pattern in one outcome need not imply a matching pattern in another. The posted arm summaries show variation across both the hip and knee cohorts. The record does not report sponsor analyses for these secondary outcomes.

Some unadjusted secondary comparisons have intervals that include zero, while the hip narcotic-consumption comparison has an interval from 0.535 to 16.67 and p = 0.037. This result is one of multiple secondary comparisons, and no multiplicity adjustment or testing hierarchy is reported. It should be treated as an unadjusted finding rather than decisive evidence. The hip length-of-stay comparison has p = 0.064 and an interval that includes zero. The knee secondary comparisons are also against the hip liposomal-bupivacaine reference, not direct comparisons between the two treatments within the knee cohort.

Secondary outcomes can be informative when interpreted in light of how they were defined, collected, and analyzed. Narcotic consumption is reported in morphine equivalents over the postoperative period up to 48 hours. Length of stay is measured in hours from surgery to discharge, with the reported timeframe capped at 140 hours. The record does not explain missing-data handling, analytic adjustments, or whether these outcomes were intended as confirmatory tests. Multiple unadjusted tests increase the chance that at least one apparently notable result will arise by chance, especially when many outcomes or contrasts are examined. Because the registry lists three outcome measures and no analyses, these results carry less inferential weight than a prespecified, fully reported analysis would.

The secondary outcomes should therefore be viewed as descriptive and exploratory in this registry record. They offer additional outcome summaries but do not convert the uncertain primary comparisons into a clear treatment conclusion. Nor can they establish that a difference in narcotic use or hospital time caused a difference in pain. Such relationships are not analyzed in the posted results.

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

• Narcotic Consumption
• Length of Stay

9. Statistical Interpretation

10. Statistical Methods Explained

The primary measure is continuous: each participant's repeated pain ratings were averaged, and those averages were summarized by group. A mean describes the center of the recorded values. The standard deviation describes how spread out participant-level values are around their group mean. These quantities answer different questions: a group can have substantial variation among participants while the mean difference between groups is estimated with a different degree of precision.

What does the mean difference represent?

Each posted comparison is expressed as the comparison arm's mean minus the reference arm's mean. A positive estimate indicates a higher mean in the named comparison arm; for pain, higher scores indicate worse pain. A negative estimate indicates a lower mean in that arm. For the hip ropivacaine contrast, the estimate is 0.07. For the two knee-arm comparisons against the hip liposomal-bupivacaine reference, the estimates are -0.48 and -0.38. These are unadjusted recalculations from the posted arm summaries, not adjusted estimates from a reported sponsor model.

The standard errors listed for the arm means reflect uncertainty in estimating each group mean, rather than the spread of participant values. The pooled standard deviation in the comparison summaries is a measure of within-group variation used in the unadjusted standardized comparison. These summary quantities do not describe the shape of the underlying distributions. The record does not report distributional checks or a statistical model for the original analysis.

How should an interval be read?

A confidence interval expresses uncertainty around an estimate. In general, a wider interval indicates less precision, while a narrower interval indicates greater precision, for the method used to form it. When an interval for a difference includes zero, the data are compatible with no difference as well as with positive or negative differences within the interval. This does not prove that the groups are the same. Nor does it establish that any particular difference is clinically important. The registry does not report a clinically important threshold for the pain score or state the confidence level used for these intervals.

What does a p value convey?

A p value is a measure of how incompatible the observed data are with a specified no-difference model, under the assumptions of the calculation. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of a difference. The unadjusted p values for the primary comparisons are 0.857, 0.215, and 0.359. They are presented without multiplicity adjustment, and the record does not report a planned testing hierarchy or a primary inferential model. Their interpretation should therefore remain tied to these particular unadjusted comparisons.

A nonsmall p value does not demonstrate equivalence, particularly when the interval still permits differences in either direction. Conversely, a smaller p value does not establish a clinically meaningful effect. Estimates, intervals, study design, outcome definition, and analysis choices all matter. For these results, the intervals and unadjusted nature of the contrasts are important context alongside the p values.

Why does the comparison reference matter?

The hip ropivacaine arm is compared with the hip liposomal-bupivacaine arm, which is a comparison within the hip cohort. In contrast, each knee arm is compared with the hip liposomal-bupivacaine arm. Those knee contrasts include both cohort and treatment differences, so they cannot answer the direct question of how the two combinations compare among knee participants. Although arm means for both knee groups are posted, a direct within-knee inferential comparison is not reported in the registry record. A new comparison should not be substituted for the posted analysis when the instruction is to describe registry results.

What can the design establish?

Random allocation can support a causal comparison when the groups, outcome ascertainment, and analysis are handled appropriately. The registry identifies the trial as randomized and double masked, but does not report the allocation process, masking procedures, adherence, or the analysis populations. The design label alone cannot establish that every potential source of bias was controlled. The parallel structure means participants were assigned to one group rather than receiving both combinations in sequence, according to the registry description.

The reported mean summaries do not show whether baseline characteristics were balanced or whether outcome availability differed between arms. The record does not report missing-data methods, adjustments for covariates, or sensitivity analyses. It also reports no sponsor analyses for the primary or secondary outcomes in the record excerpted for these results. Accordingly, the unadjusted calculations are useful for describing the posted group summaries, but they cannot fill gaps in the trial's planned or complete statistical analysis.

11. Confidence Intervals and Precision

The uncertainty intervals for the primary pain comparisons are wide enough to include zero. For the hip comparison, the estimate is 0.07 and the interval ranges from -0.694 to 0.834. For the knee liposomal-bupivacaine arm relative to the hip reference, the estimate is -0.48 and the interval ranges from -1.239 to 0.279. For the knee ropivacaine arm relative to the hip reference, the estimate is -0.38 and the interval ranges from -1.192 to 0.432. These intervals show that the estimates are not precise enough to pin down a single difference.

Because zero falls within each interval, the results are compatible with no difference under the interval calculation. They are also compatible with effects in either direction within the respective bounds. That uncertainty is not the same as proof that the groups are identical. The registry does not give a threshold for a clinically important difference, so the clinical importance of the range of values cannot be determined from the record alone.

The group standard deviations for pain are 2.22, 2.01, 2.0, and 2.3 across the four arms. These describe variability among participant-level mean scores, whereas the intervals describe uncertainty about group contrasts. The record does not provide participant-level data or the pattern of scores at each four-hour assessment. It therefore cannot show whether the uncertainty is driven by a particular part of the score distribution, changes over time, or missing assessments.

Precision also depends on which groups are contrasted. The hip estimate is a within-cohort comparison. The two knee estimates use the hip liposomal-bupivacaine arm as reference and consequently do not provide a direct treatment contrast within the knee cohort. The precision intervals cannot resolve that design and comparison limitation.

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 sample-size illustrations are planning calculations based on the observed effects, not the trial's original design assumptions. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and a target effect set to the stated fraction of the observed effect. The figures are participants per arm, not total participants or total events. These are continuous outcomes, and the planning figures are therefore reported as participants per arm.

The 80% power column gives the estimated number of participants per arm for a hypothetical future study to have an 80% chance of detecting the stated effect under the planning assumptions, if that effect and the assumptions are appropriate. The 90% power column uses a higher target chance of detection and consequently generally requires more participants. For example, planning for 100% of the observed hip pain effect gives 14,391 participants per arm for 80% power and 19,265 participants per arm for 90% power. These are illustrations, not recommendations or observed trial results.

Planning for 75% of the observed effect or planning for 50% of the observed effect assumes a smaller difference to detect. Smaller effects are harder to distinguish from random variation, so they require more participants. For the knee liposomal-bupivacaine pain comparison, the corresponding figures for 80% power are 305, 542, and 1,218 participants per arm for planning at 100%, 75%, and 50% of the observed effect. The figures are particularly sensitive to the estimated effect; small observed effects can yield very large planning estimates.

These calculations are not observed power. The trial's own sample-size justification and original design assumptions are not reported in the registry record. The illustrations use the posted observed effects and should be read as hypothetical planning scenarios, not as an account of whether the completed trial was adequately designed or as a retrospective measure of its success.

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 = 0.070; pooled standard deviation σ = 2.119.
2. n = 2 × (1.96 + 0.842)² × 2.119² / 0.070² = 14,390.4, rounded up to 14,391 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 <- 0.0700000000000003                      # observed difference in means
sigma <- 2.11941212571333                     # 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(2543801)
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 = 14,391 (80% power), 19,265 (90% power)
 75% of observed effect: n per arm = 25,583 (80% power), 34,249 (90% power)
 50% of observed effect: n per arm = 57,562 (80% power), 77,059 (90% power)
power.t.test: 14391.3 
Simulated power at n = 14,391 per arm: 0.795 (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 lists a primary pain outcome and two secondary outcomes, with multiple arm-level comparisons. It does not report a multiplicity-control procedure, a hierarchy for testing outcomes, or an allocation of the overall type I error across comparisons. The posted p values are unadjusted. When several comparisons are examined, the chance of at least one apparently unusual result can increase; this general issue is why interpretation of an isolated unadjusted secondary p value should be cautious. Whether any adjustment was planned or conducted is not reported in the registry record.

The record also reports no outcome analyses from the sponsor. It does not state which analysis populations were intended, whether the analysis followed intention-to-treat principles, or whether any participants were excluded from specific outcome calculations. The posted outcome arm sizes are available, but details about randomization status, treatment receipt, protocol deviations, and outcome availability are not reported in the registry record. These gaps limit assessment of how the analyzed groups relate to all randomized participants.

Missing-data procedures are not reported. For pain, the endpoint averages repeated postoperative ratings, but the record does not state how the average was calculated when a rating was absent, whether participants needed a minimum number of ratings, or whether missing outcome values were imputed. For narcotic consumption and length of stay, the handling of missing values and censoring is also not reported. Without those details, it is not possible to assess whether missingness could have affected the group summaries.

The record does not describe prespecified covariate adjustment, assumptions about outcome distributions, sensitivity analyses, or subgroup analysis plans. It also does not state whether the posted comparisons were specified before the results were known. These are not proof that such procedures were absent from the full trial conduct; they are details not reported in the registry record. The unadjusted summary-based comparisons can be described as such, but should not be mistaken for a complete statistical analysis plan or a comprehensive account of missingness and multiplicity.

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.

The adverse-event record lists 0 serious adverse events and 0 deaths in each of the four groups. The numbers at risk for serious events are 60 in the hip liposomal-bupivacaine group, 58 in the hip ropivacaine group, 59 in the knee liposomal-bupivacaine group, and 59 in the knee ropivacaine group. The record also lists 0 other adverse events in each group, with the same group counts at risk.

These figures describe what was reported in the registry record; they do not show that no events occurred outside the record's reporting scope or observation period. Definitions, collection procedures, follow-up duration for adverse events, and attribution criteria are not reported in the registry record. With no events recorded in these groups, the results also cannot precisely characterize the rate or range of possible uncommon harms. The absence of a listed event should not be interpreted as proof of absence of risk, nor as a comparative safety analysis between the combinations.

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

The posted results describe average pain scores in four arms and unadjusted comparisons calculated from the arm summaries. The hip group means are close, and the knee group means are also close to one another. The intervals for all three primary comparisons include zero, so the summaries do not establish a difference between the compared means. At the same time, they do not establish equivalence or rule out potentially relevant differences. The registry does not report a threshold for clinical importance.

The results do not show the experience of every participant. Group means condense repeated reports into a summary, and standard deviations indicate variation among participant averages. The record does not provide individual data, distributions, or pain trajectories across the repeated assessments. It also does not report the sponsor's inferential analysis, missing-data methods, or analysis populations. Those omissions constrain how confidently the unadjusted comparisons can be interpreted.

The comparisons for the knee groups require particular care. Each uses the hip liposomal-bupivacaine arm as a reference. They therefore do not directly answer whether the two injection combinations differ within the knee cohort. The arm-level knee means are posted, but a direct within-knee analysis is not reported in the registry record.

The secondary outcomes are not a substitute for the primary result. Their unadjusted comparisons include multiple outcomes and contrasts, and no multiplicity procedure or confirmatory testing plan is reported. The observed secondary pattern cannot establish a causal relationship between pain, narcotic consumption, or length of stay.

Overall, the registry supports a narrow descriptive reading of the posted group summaries. It does not justify claims that one regimen works better, that the regimens are interchangeable, or that the results apply to all arthroplasty patients. The trial's randomized and double-masked designation is relevant context, but details needed to evaluate implementation and analysis are not reported in the registry record. Conclusions should remain proportionate to the comparisons and information actually posted.

17. Why This Trial Matters Statistically

This trial is statistically instructive because its record combines a randomized design label with outcome summaries that require careful attention to the comparison being made. The hip arms are compared within the hip cohort, while the knee arms are each contrasted with a hip arm. A comparison label alone can make results look like treatment contrasts, but the cohort used as the reference determines what question the estimate answers. The knee estimates cannot isolate the treatment difference within the knee cohort.

The primary outcome also illustrates the distinction between group variability and uncertainty in a group difference. Standard deviations describe how participant-level average pain scores vary within arms. Intervals around mean differences describe uncertainty in the contrast. All three intervals include zero, but this does not prove equivalence; the registry does not provide a clinically important threshold or an equivalence framework.

The secondary findings illustrate why multiplicity and analysis plans matter. The record lists multiple outcomes and comparisons, but does not report adjustment for multiple testing or sponsor analyses. A single unadjusted p value should not be elevated above the broader evidence pattern without knowing whether it was prespecified and how other tests were handled.

Finally, the planning illustrations based on observed effects show how strongly sample-size estimates can depend on the effect assumed for a future study. They are not the trial's original design justification and are not observed power. Distinguishing descriptive results, unadjusted recalculations, and prospective planning scenarios helps prevent these different statistical quantities from being treated as interchangeable evidence.

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.

Several limitations are specific to interpreting this registry record. The results are separated into hip and knee cohorts, but the posted comparisons for the knee arms use the hip liposomal-bupivacaine group as the reference. Consequently, the record does not provide a direct comparison of the two injection combinations within the knee cohort. The knee contrast estimates combine cohort and treatment differences.

The pain endpoint is an average of repeated self-reports over the postoperative period up to 48 hours. The record does not report the number of completed ratings per participant, how missing ratings were handled, or whether all participants contributed to the average. A single average also does not show whether pain differed at particular assessment times.

The record provides arm means, standard deviations, and summary-based unadjusted contrasts, but no sponsor analyses. It does not report the original sample-size justification, analysis model, analysis populations, adjustment for covariates, missing-data procedures, or multiplicity plan. It also does not state a clinically important threshold for pain differences or an equivalence margin.

Although the trial is identified as randomized and double masked, details of allocation and masking procedures are not reported in the registry record. Participant characteristics and other information needed to assess group comparability are not included with these results. Adverse-event definitions and collection procedures are likewise not reported. These limitations do not demonstrate that the procedures were inadequate; they mean that the registry record does not allow those aspects to be evaluated.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Clinical Trial of Two Periarticular Multimodal Drug Injections in Total Hip and Knee Arthroplasty — NCT02543801.
• Registry record last updated 2019-10-18; status last verified 2019-10.
• Results first posted 2019-10-18.
• 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

The registry record describes a completed, randomized, double-masked, parallel-group phase 4 trial sponsored by Kootenai Health, with 239 participants undergoing total hip or knee arthroplasty. It compares periarticular combinations containing either liposomal bupivacaine plus bupivacaine or ropivacaine, alongside clonidine, epinephrine, and ketorolac.

The primary outcome is participant-level mean pain score, averaged from repeated postoperative ratings up to 48 hours. The posted arm summaries and unadjusted comparisons show intervals that include zero for all three listed primary contrasts. The knee comparisons use the hip liposomal-bupivacaine arm as their reference, so they are not direct within-knee treatment comparisons.

Narcotic consumption and length of stay are also posted as secondary outcomes. The registry record does not report sponsor analyses, the original sample-size rationale, missing-data methods, analysis populations, or multiplicity procedures. The results are therefore best read as posted summaries and unadjusted comparisons with important limits on inference.