Comparison of Levobupivacaine and Ropivacaine for Femoral Neural Block: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparison of Levobupivacaine and Ropivacaine for Femoral Neural Block (NCT01172197), a randomized phase 4 study. The primary outcome is Pain.

2. Clinical Question

In plain terms, the study was intended to compare two local anaesthetics in the setting of continuous femoral perineural infusion after knee replacement. Its rationale describes interest in pain relief alongside quadriceps motor block, with electromyogram measurement mentioned in the summary. However, the record reports only one outcome measure, titled “Pain.” It does not post an outcome result for motor block or an estimate of the relative dose needed to reach a specified level of pain relief.

The clinical question is therefore narrower in the posted results than the broader objective described in the official title and summary. The outcome data state the number meeting the pain-score criterion in each arm at the specified assessment time. They do not establish a comparative dose-response relationship. The registry record does not report enough comparative outcome information to quantify how the two drugs differed on the primary endpoint.

3. Trial Design

The registry identifies this as a randomized, single-blind, parallel-group, phase 4 study. It lists NHS Tayside as the sponsor, enrollment of 14, and a terminated status. The study start is recorded as 2009-01 and primary completion as 2011-10. The meaning of single blinding in practice—such as which people were unaware of treatment assignment—is not reported in the registry record.

The two arms are ropivacaine and levobupivacaine. Each arm description says local anaesthetic bolus and infusion. The official title identifies the route and context as femoral perineural infusion for pain relief after total knee replacement. The record does not give the bolus or infusion doses, the infusion duration, or a detailed description of the allocation sequence or concealment procedures. Those details should not be inferred from the randomized designation alone.

The record’s study summary describes the aim as developing an anaesthetic regimen offering pain relief while allowing mobilisation, and says the investigators aimed to compare median effective doses. It also mentions objective assessment of quadriceps motor block using an electromyogram. The ending of the posted summary is incomplete, and details beyond its visible text are not reported in the registry record. No motor-block outcome appears among the posted outcome measures.

The registry lists one outcome measure and no analyses. The posted primary endpoint is a participant count for pain on movement scored as 0 at 30 hours after the perineural infusion began. For that outcome, the results list 7 participants in each arm and a value of 7 for each arm. A formal two-arm comparison is not estimable from the registry results, as indicated by the stated reason that values are missing or not estimable for a binary endpoint comparison.

Although enrollment is recorded as 14, this should not be read as proof that every enrolled participant contributed to the primary outcome. The record does not provide a participant flow diagram, exclusions, withdrawals, or arm-specific analysis-population definitions. It also does not explain why the study was terminated. The termination status is relevant to the record’s context, but the reason for termination is not reported.

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: Nil to report

Overall Study

Analysis population for the primary outcome, as defined in the registry: Knee replacement. All obtained pain relief defined as pain score = 0 on a verbal pain rating scale

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, measured over 30 hours.

The primary endpoint is the number of participants achieving pain on movement of the knee scored as 0 on a verbal pain rating scale. The assessment is specified for 30 hours after the start of the perineural infusion. The registry reports the unit as participants and classifies the measure as a count of participants with an event. Here, the event is meeting the stated pain criterion, not an adverse event.

A threshold outcome such as this can make a clinical state easy to describe: the result counts participants who meet a prespecified definition, rather than reporting each person’s full pain score. It can be useful when the scientific question is about reaching a particular level of symptom relief. This is a general explanation of threshold outcomes; the registry record does not explain why this particular threshold or assessment time was selected.

The posted values are 7 for ropivacaine and 7 for levobupivacaine, with 7 listed in each arm. These are arm-level counts. The registry does not report the individual pain scores, the distribution of scores, or an estimated comparative effect with uncertainty. It also does not report a median effective dose as an endpoint result. As a result, the endpoint figures alone do not provide a dose-response estimate or a precise statistical comparison between the treatments.

The assessment is specifically pain on movement, rather than pain at rest. The record does not describe the movement procedure, the verbal scale’s full range, who assessed the outcome, or whether the assessment was conducted under a standardized protocol. Such details would help readers understand how reproducible and sensitive the endpoint may be, but they are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a randomized parallel-group design. In a parallel-group trial, participants are assigned to one treatment group and outcomes are compared between groups. Randomization is intended, in general, to reduce systematic differences in baseline characteristics between treatment groups. It does not guarantee that groups are identical, particularly in a small study. Details of the randomization method and allocation concealment are not reported in the registry record.

Single-blind describes a trial in which at least one party is intended not to know the assigned treatment. The record does not say who was blinded, how blinding was maintained, or whether participants or assessors could identify treatment. These details matter because knowledge of assignment can influence behavior, assessment, or reporting. The designation alone does not establish that outcome assessment was protected from every source of bias.

What kind of outcome is reported?

The primary endpoint is binary at the participant level: a person either meets the specified criterion of pain on movement scored as 0 at the assessment time, or does not. The results are then reported as counts in each arm. This differs from a continuous outcome, such as a score that can take a range of values, and from a time-to-event outcome, which incorporates how long it takes for an event to occur.

For a binary endpoint, a comparative analysis commonly estimates a contrast between the groups using a measure suited to the question and analysis plan. General examples include a difference in event probabilities or a relative measure. The registry does not post such an estimate for this endpoint. It explicitly marks a two-arm comparison as not estimable. No additional comparison should be constructed from the displayed counts in place of the missing registry analysis.

Why does an estimate need uncertainty?

An observed count is one realization from the participants included in a study. A comparative estimate describes the contrast in the observed data, while a standard error or confidence interval conveys uncertainty about that contrast. General statistical uncertainty depends on factors such as the amount of information and the variability of the outcome. In a binary-outcome analysis, the number of participants meeting and not meeting the criterion in each group is relevant. The registry does not provide an uncertainty estimate for the primary comparison.

A confidence interval is not a statement that all possible values are equally plausible, nor is it a measure of clinical importance. It is an interval constructed according to a statistical method and its assumptions. A narrow interval generally indicates greater precision than a wide interval, but interpretation still depends on the outcome and context. Since no interval is reported for the primary contrast, its precision cannot be assessed from the registry record.

What does not estimable mean in this record?

The posted reason says that values are missing or not estimable for a two-arm comparison of the binary endpoint. That is the record’s stated status; it does not explain which data or analysis issue led to it. The arm-level counts remain listed, but they do not come with an estimated contrast or inferential result. The record does not report an alternative method, a model, adjustment variables, or an explanation of why a comparison could not be calculated.

It would be inappropriate to treat the listed counts as a formal test or to infer a p-value. It would also be inappropriate to infer equivalence from the absence of a comparative estimate. Equivalence requires a defined margin and an analysis designed to assess whether effects lie within that margin; neither is reported in the registry record.

What do the planning assumptions mean?

The registry describes sample-size planning illustrations as based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. Such illustrations are hypothetical planning exercises: they describe participant requirements under selected assumptions, not what the trial actually observed and not the probability that the study result is true.

In particular, a planning illustration is not “observed power.” Observed power is often misunderstood as a retrospective measure of whether a result is credible. General statistical practice gives more useful attention to the estimated effect and its uncertainty. In this record, an estimable primary contrast and its uncertainty are not reported, so the planning assumptions do not resolve the interpretive gap. The registry’s explanation also distinguishes participant counts per arm for most outcomes from total event counts for time-to-event outcomes; the primary endpoint is a participant count.

The record does not report the trial’s own sample-size justification, target enrollment rationale, statistical analysis plan, interim analyses, or any adjustment for covariates. The planning assumptions described for the illustrations should not be mistaken for those missing protocol details.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Ropivacaine", "Levobupivacaine")
n      <- c(7, 7)
events <- c(7, 7)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Ropivacaine  7  7  100.0  59.0  100.0  64.6  100.0  63.1  99.7
ARM  Levobupivacaine  7  7  100.0  59.0  100.0  64.6  100.0  63.1  99.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure, the primary pain endpoint, and reports no analyses. No secondary outcomes are posted. This means the record does not provide a set of reported endpoint analyses from which to assess whether multiple statistical tests were conducted or how any multiplicity was handled. Whether the original protocol included additional outcomes, planned contrasts, or interim looks is not reported in the registry record.

Multiplicity is a general statistical concern when several outcomes, time points, treatment comparisons, or analytic choices are tested. Conducting many tests can increase the chance of at least one apparently unusual result by chance. Researchers may address this through prespecified testing strategies or adjustments, but the appropriate approach depends on the study’s aims. No multiplicity strategy is reported in the registry record, so none should be assumed.

Missing-data handling is also not reported. The registry provides an arm count for the primary endpoint but does not state whether any participants lacked outcome data, how missing assessments were treated, or whether imputation was used. It does not report reasons for missingness or a sensitivity analysis. A listed group size and endpoint count do not by themselves establish the completeness of outcome ascertainment.

The analysis population is not specified. The record does not say whether the reported results follow an intention-to-treat approach, a per-protocol approach, or another definition. It also does not explain whether participants were analyzed in their randomized groups or whether any exclusions occurred. These definitions can affect interpretation, especially when treatment discontinuation or protocol deviations occur, but such details are not available in the registry record.

Finally, the reason for termination and the timing of the decision are not reported. Without that context, readers cannot determine whether termination affected the planned analysis or outcome reporting. These omissions limit assessment of analysis choices; they are not evidence that any particular problem occurred.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

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

The registry’s safety entries list 0 serious adverse events, 0 other adverse events, and 0 deaths in each arm. For each of those categories, the record lists 7 participants at risk in the ropivacaine arm and 7 in the levobupivacaine arm. These are the posted event counts and at-risk figures, not a comparative safety analysis.

A reported count of 0 means that no events in that category are recorded in the registry results for the listed group. It does not establish that an intervention has no risk. In general, safety interpretation depends on how events were defined, how they were collected, the observation period, completeness of follow-up, and the amount of information available. The adverse-event observation window and detailed collection methods are not reported in the registry record.

No serious adverse-event terms are listed. The record does not provide event descriptions, severity criteria, timing, relatedness assessments, or a statistical comparison between the arms. The figures should therefore be read narrowly as registry-reported counts, rather than as evidence of equal safety or a definitive safety assessment.

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

The posted results show that the registry lists 7 participants meeting the primary pain criterion in each arm, with 7 participants listed in each arm. The endpoint is pain on movement scored as 0 at 30 hours after the infusion began. These figures describe the recorded arm-level counts at that assessment time.

They do not provide an estimable comparison between levobupivacaine and ropivacaine. The registry states that values are missing or not estimable for a two-arm comparison of this binary endpoint. No effect estimate, confidence interval, or p-value is reported. The counts therefore cannot establish whether the treatments differ, nor can they establish equivalence or non-inferiority.

The official title and summary describe a question about molar median effective dose, and the summary also mentions motor-block measurement. The posted outcome result does not report a median effective dose, a dose-response model, or a motor-block result. It consequently does not answer those broader questions on the basis of the available registry results.

General statistical interpretation distinguishes absence of evidence for a difference from evidence that differences are small enough to be unimportant. The latter requires an appropriate design, a defined threshold for importance, and sufficiently precise estimates. Those elements are not reported for this primary comparison. The lack of an estimable comparison should be understood as a limitation of the posted result, not as a finding that the treatments perform the same.

The registry’s terminated status adds context but does not explain the study’s outcome. The reason for termination, the completeness of follow-up, and the analysis population are not reported. The findings should therefore be described only at the level of the counts and reporting status, without claims about treatment benefit, harm, or clinical choice.

14. Why This Trial Matters Statistically

This record illustrates the difference between having outcome counts and having a usable comparative estimate. The primary result gives a count for each treatment arm, but the registry does not report an estimable two-arm comparison. For statistical interpretation, the contrast and its uncertainty are often central: they show the direction and magnitude of the observed group difference and how precisely it is estimated. Without them, readers cannot assess the comparative result in the usual inferential terms.

The distinction is especially important because the trial’s stated objective concerns median effective dose. A dose comparison asks more than whether participants in each arm met one pain threshold at one time. It needs information connecting administered dose to response and a suitable analysis of that relationship. The posted endpoint does not supply such an estimate. The record also mentions quadriceps motor block in its summary, but no motor-block result is posted as an outcome.

The registry’s stated planning assumptions offer another useful statistical distinction. Sample-size planning illustrations are conditional on assumptions about an effect and analysis; they are not observed trial results and do not provide retrospective evidence that the study was adequately powered. No trial-specific sample-size justification is reported in the registry record.

Finally, the record shows why reporting details matter. Information about the analysis population, missing outcomes, blinding procedures, and termination reason would help readers understand how the reported counts were generated and what inferences are supported. Their absence does not establish that the study was conducted improperly. It does mean that the public registry record supports a limited statistical description rather than a full comparative assessment.

15. 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 main limitation for interpretation is that the registry reports arm-level binary outcome counts but marks the two-arm comparison as not estimable. No comparative effect estimate, confidence interval, or test result is available. Consequently, the magnitude and precision of any treatment contrast cannot be assessed from the posted results.

The endpoint is limited to a single stated assessment at 30 hours after the perineural infusion began. The record does not report pain outcomes at other times or the full distribution of verbal pain ratings. It also does not report the dose-response result implied by the official title’s median-effective-dose objective. Although the summary mentions quadriceps motor block assessment, no such outcome is posted.

Enrollment is recorded as 14, but participant flow, outcome completeness, withdrawals, exclusions, and analysis-population definitions are not reported. Missing-data methods and reasons for any missing outcomes are also not reported. Therefore, the relationship between enrollment and the participants contributing to each result cannot be fully evaluated.

The registry identifies the study as randomized and single blind, but it does not provide the randomization procedure, allocation concealment details, or the identity of the blinded party. Treatment doses and administration details beyond bolus and infusion are not reported. The reason for the terminated status is not reported, so its implications for conduct or analysis cannot be established.

These are limitations of what can be concluded from the registry record. They do not show that an unreported procedure was absent or that an unreported issue occurred. They define the boundary between the available counts and a more complete evaluation of comparative efficacy, dose response, and safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Comparison of Levobupivacaine and Ropivacaine for Femoral Neural Block — NCT01172197.
• Registry record last updated 2018-05-09; status last verified 2018-04.
• Results first posted 2018-05-09.
• 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.

19. Record Summary

NCT01172197 is a randomized, single-blind, parallel-group, phase 4 study sponsored by NHS Tayside. It compares levobupivacaine with ropivacaine, each described as a local anaesthetic bolus and infusion, in the context of femoral perineural infusion after total knee replacement. The registry records enrollment of 14, a start date of 2009-01, primary completion in 2011-10, and terminated status.

The one posted outcome measure is the number of participants with pain on movement scored as 0 on a verbal pain rating scale at 30 hours after the infusion began. The results list 7 for each arm and 7 participants in each arm. A two-arm comparison is marked not estimable. The record provides no comparative effect estimate or uncertainty interval.

The reason for termination, analysis population, missing-data approach, and trial-specific statistical plan are not reported in the registry record. The posted results therefore support description of the listed counts, but not a quantified comparison of the treatments or a dose-effect conclusion.