Lusedra (Fospropofol Disodium) for Minimal to Moderate Sedation for Regional Anesthesia Block Prior to Orthopedic Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Lusedra (Fospropofol Disodium) for Minimal to Moderate Sedation for Regional Anesthesia Block Prior to Orthopedic Surgery (NCT01195103), a randomized phase 4 study. The primary outcome is Percentage of Participants Achieving Sedation Within 4 Minutes.

2. Clinical Question

The clinical question is about the timely achievement of a procedural sedation target, not simply whether a participant received a sedative or reached a particular score at any later time. Success required both a Modified Observer’s Assessment of Alertness/Sedation Scale score of 4 or lower and initiation of the block within the stated time window. The registry describes a score of 4 as a lethargic response to a name spoken in a normal tone.

The posted outcome percentages are 100.0% for 10 mg/kg Lusedra, 50.0% for 6.5 mg/kg Lusedra, and 40.0% for placebo plus midazolam. The corresponding reported group sizes are 5, 2, and 5 participants. The registry does not post an analysis comparing these groups, so the percentages describe the observed outcome in each arm rather than establishing a statistical difference. With such small reported groups, individual participants’ outcomes have a substantial influence on each percentage.

3. Trial Design

The registry describes a Phase 4, randomized, quadruple-masked, parallel-group study. It lists Mayo Clinic as the sponsor and an enrollment of 13. The study is marked terminated. Its recorded start is 2011-02, and its primary completion is 2011-03.

Three arms have posted descriptions and primary-outcome results: 10 mg/kg Lusedra, 6.5 mg/kg Lusedra, and placebo plus midazolam. The Lusedra arms used an initial bolus at the stated dose; the comparator arm used a placebo initial bolus with midazolam based on the participant’s weight. Fentanyl also appears in the registry’s intervention list, but the record does not describe a separate fentanyl arm or post an outcome for one. The reason for its listing is not reported in the registry record.

Randomization means assignment to study groups was described as random, while parallel-group design means the listed groups were compared as separate arms. Quadruple masking indicates the record’s masking designation, but it does not identify which specific people were masked or explain how masking was maintained. Further allocation procedures, masking details, recruitment information, and the reasons for termination are not reported in the registry record.

The total enrollment is 13, while the primary-outcome arm results list group sizes of 5, 2, and 5. The registry does not explain the difference between the overall enrollment and the group sizes reported for this outcome. It also does not report whether every enrolled participant received assigned treatment, completed the procedure, or contributed data to the primary outcome. Those details matter when interpreting group percentages, but cannot be inferred from the 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

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 Percentage of Participants Achieving Sedation Within 4 Minutes, measured over approximately 4 minutes after administration of first bolus of study drug.

The primary endpoint is the percentage of participants who met a combined sedation-and-procedure criterion within approximately 4 minutes after the first bolus of study drug. A participant counted toward the endpoint only if the Modified Observer’s Assessment of Alertness/Sedation Scale score was 4 or lower and the block procedure had been initiated within that time window. The scale ranges from 0, described as no response to deep stimulus, to 6, described as agitated. A score of 4 is defined as a lethargic response to a name spoken in a normal tone.

Combining a sedation assessment with a procedural milestone makes the endpoint relevant to the immediate task: it captures both a specified level of responsiveness and readiness for the block to begin. This is a general rationale for such a measure, not a claim that the registry reports a separate validation or rationale for selecting it. The registry reports the endpoint as a percentage, with results of 100.0%, 50.0%, and 40.0% in the three listed arms.

As a binary outcome, each participant either met both criteria within the stated window or did not. The endpoint does not describe the exact time for each participant, the degree of sedation beyond the threshold, or outcomes after the block began. These additional details 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 binary percentage outcome: the percentage of participants who met the primary endpoint. In general, a binary outcome classifies each participant into one of two categories, such as meeting or not meeting a defined criterion. The endpoint required both a sedation score of 4 or lower and initiation of the block within approximately 4 minutes after the first bolus. The reported percentages summarize the share meeting both conditions in each arm.

What do the percentages describe?

Each arm’s percentage is a descriptive summary of the participants with a reported result in that arm. The registry pairs those values with group sizes: 5 for 10 mg/kg Lusedra, 2 for 6.5 mg/kg Lusedra, and 5 for placebo plus midazolam. A percentage does not show how uncertain the estimate is on its own. General statistical context: the uncertainty around a proportion depends in part on the number of observations, so a proportion based on a very small group can be imprecise. No uncertainty intervals are reported for these endpoint values.

How would an arm comparison be interpreted?

A comparison would ordinarily quantify how the chance of meeting the endpoint differed between treatment groups and describe uncertainty around that estimate. The registry does not post such a comparison, a test statistic, a p-value, or a confidence interval. It also does not post adjusted analyses. As a result, the arm percentages can be described individually, but the registry does not support a claim that a formal statistical test found a difference between any pair of arms.

General statistical context: a confidence interval gives a range of values compatible with the data under the assumptions of the analysis. It helps distinguish a precise estimate from one with considerable uncertainty. A p-value, when used, measures how unusual data at least as incompatible with a specified null hypothesis would be under that hypothesis and the model assumptions. Neither measure is posted for this outcome. Their absence should not be replaced by an informal judgment based solely on which percentage is larger.

What does randomization contribute?

Random assignment is intended to make treatment groups comparable, on average, with respect to factors known and unknown at the time of assignment. It does not guarantee that small groups will have similar characteristics, and it cannot remove uncertainty created by limited information. The registry identifies the study as randomized but does not report the sequence-generation method, allocation concealment, baseline characteristics, or details of the analysis population. Those elements are relevant to evaluating how well the randomized design was implemented and how the posted results should be interpreted.

Why is the small sample important?

The posted outcome groups contain only a few participants. General statistical context: with a small sample, each participant’s outcome has a larger influence on the group estimate than it would in a much larger sample. This makes percentages particularly sensitive to individual outcomes and generally limits the precision available for comparisons. The record does not report a sample-size justification or a planned target for statistical precision, so the adequacy of enrollment for the primary question cannot be assessed from the registry entry.

The sample-size assumptions in the record describe a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such an illustration is not the trial’s own design justification, does not describe the trial’s actual analysis, and is not observed power. The registry does not report the trial’s original sample-size calculation or explain how any planning illustration relates to the study’s enrollment.

What can be learned from the posted analysis status?

The registry lists no posted analyses. Thus, there is no sponsor-reported treatment-effect estimate or inferential result to summarize for the primary endpoint. It would be inappropriate to substitute an unadjusted calculation from the arm summaries for a sponsor analysis: the registry supplies no analysis to verify, no stated modeling approach, and no explanation of which participants were included. The record also does not report interim analyses, stopping rules, or a statistical analysis plan.

General statistical context: methods for binary outcomes can account for different designs and analysis goals, but choosing a method requires details about the planned comparison and data. No method for comparing the arms is described in the registry record. Accordingly, the clearest statistical account is limited to the observed arm percentages, their reported group sizes, and the absence of posted inferential results.

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("10 mg/kg Lusedra", "6.5 mg/kg Lusedra", "Placebo + Midazolam")
n      <- c(5, 2, 5)
events <- c(5, 1, 2)
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  10 mg/kg Lusedra  5  5  100.0  47.8  100.0  56.6  100.0  54.1  99.6
ARM  6.5 mg/kg Lusedra  2  1  50.0  1.3  98.7  9.5  90.5  9.4  90.6
ARM  Placebo + Midazolam  5  2  40.0  5.3  85.3  11.8  76.9  11.8  77.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and no secondary outcomes. It reports no posted analyses. The record does not state whether the primary outcome was the only outcome planned in the protocol, whether additional outcomes were measured but not registered, or whether multiple comparisons were anticipated. A multiplicity strategy, such as a planned adjustment for testing several outcomes or contrasts, is not reported in the registry record.

Missing-data handling is also not described. The record does not say how participants with unavailable endpoint assessments, incomplete procedures, or other missing observations were treated. It does not provide a participant flow account or explain whether the reported group sizes represent all randomized participants, those treated, or those with evaluable endpoint data. The listed arm sizes should therefore be read as the group sizes accompanying the posted results, not assumed to describe every analysis population.

The registry does not specify an intention-to-treat, per-protocol, or safety population for the primary outcome. It also does not explain whether any participants were excluded from an analysis or how deviations from assigned treatment were handled. These details are important because the population analyzed can affect interpretation, particularly in a randomized study. Without them, the reason the overall enrollment is 13 while the endpoint groups list sizes of 5, 2, and 5 is not reported in the registry record.

No assumptions about missing outcomes, imputation, interim monitoring, or multiplicity can be inferred from the posted entry. The absence of these details limits assessment of the analysis but does not establish that any particular procedure was or was not used outside what the registry reports.

12. Safety Results

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

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: apnea (20.0%).

The registry reports serious adverse events in 1 participant in the 10 mg/kg Lusedra group, none in the 6.5 mg/kg Lusedra group, and none in the placebo-plus-midazolam group. The corresponding numbers at risk are 5, 2, and 5. These are event counts as posted; the registry does not provide a safety comparison or an inferential analysis.

Apnea is listed among the serious adverse-event terms at 20.0%. The record does not identify the arm associated with that term in the listed summary, so it should not be attributed to a particular group from this information alone. The registry also reports other adverse events in 5 participants in the 10 mg/kg group, 1 participant in the 6.5 mg/kg group, and 2 participants in the placebo-plus-midazolam group, with 5, 2, and 5 at risk, respectively.

Adverse-event counts are not, by themselves, a basis for comparing safety across these small groups. The record does not supply event-level descriptions, timing, severity details beyond the serious-event classification, or a statistical comparison. Deaths are not reported in the registry record.

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

The posted results show that the primary endpoint was met by 100.0% of participants in the 10 mg/kg Lusedra arm, 50.0% in the 6.5 mg/kg Lusedra arm, and 40.0% in the placebo-plus-midazolam arm. The outcome required both a sedation score of 4 or lower and initiation of the block within approximately 4 minutes after the initial study-drug bolus. The reported arm sizes are 5, 2, and 5 participants, respectively.

These observations describe what was recorded in the listed groups. They do not establish the size or certainty of a treatment effect. The registry reports no analysis comparing arms, no confidence intervals, and no p-values for the primary outcome. The very small group sizes also mean that the percentages should not be treated as precise estimates of what would occur in a broader population. This statistical context does not imply a particular result beyond the posted data.

The results do not establish that a regimen caused faster sedation, that a difference between the observed percentages is statistically reliable, or that the outcome would be reproduced in other settings. They also do not address outcomes outside the endpoint’s definition, such as the full duration or quality of sedation. The entry does not provide enough information to assess whether every enrolled participant contributed to the endpoint, or how any missing data were handled.

The status is terminated, but the reason for termination is not reported in the registry record. The record also does not provide a protocol rationale, detailed study conduct information, or a complete analysis plan. Therefore, the appropriate interpretation is descriptive and limited: the registry records these percentages and group sizes, while leaving important questions about precision, analysis, and generalizability unresolved.

14. Why This Trial Matters Statistically

This study illustrates how a registry result can be numerically clear but statistically difficult to interpret. The primary endpoint is explicitly defined as a participant-level success criterion, and the registry gives a percentage and group size for each of the three listed arms. At the same time, the groups are very small and no inferential analysis is posted. The percentages therefore convey the observed outcomes without showing how uncertain comparisons between arms may be.

The endpoint also demonstrates a distinction between a clinical process measure and a broad patient outcome. It combines a specified level of responsiveness with the start of the regional anesthesia block within approximately 4 minutes. That makes the measure focused on procedural readiness in a defined window. It does not capture every aspect of sedation or describe later outcomes, and the registry does not report additional outcome measures to broaden the assessment.

For biostatisticians and clinical researchers, the record underscores the value of complete reporting alongside headline percentages. Information about participant flow, analysis populations, missing outcomes, the planned comparison, precision estimates, and the reason for termination would help readers evaluate the result. Those details are not reported in the registry record. Their absence is particularly consequential when only a few participants are listed in each arm, because readers need context to judge both the reliability and scope of the estimates.

The statistical lesson is not that a particular arm performed better in a general or definitive sense. Rather, descriptive proportions, trial design labels, and an endpoint definition do not substitute for a prespecified analysis and uncertainty assessment. This record offers a concrete example of why effect estimates, confidence intervals, analysis populations, and transparent accounting of missing data matter when interpreting randomized trial results.

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 registry marks the study as terminated, but does not report why it ended or whether termination affected enrollment, follow-up, or planned analyses. The overall enrollment is 13, while the primary outcome lists groups of 5, 2, and 5 participants; the record does not explain how those figures relate or describe participant flow. It does not report baseline characteristics, eligibility criteria in detail, or the number of participants who completed the procedure.

Only the primary outcome is posted, and no analyses are listed. There are no reported confidence intervals, p-values, adjusted comparisons, or analysis-population definitions. Missing-data methods, protocol deviations, interim analyses, and the statistical analysis plan are not reported in the registry record. The registry also does not describe how randomization was carried out or which people were masked under the quadruple-masking designation.

The 6.5 mg/kg arm has a reported group size of 2, which makes its percentage especially sensitive to individual outcomes. More broadly, the small groups restrict the precision and scope of any interpretation. The registry does not report a sample-size justification, so it is not possible to assess the planned statistical precision from this entry. The listed sample-size assumptions are described as a planning illustration based on the observed effect, not as the trial’s own design justification.

Safety information is limited to the posted event counts and a serious adverse-event term summary. The registry does not provide a comparative safety analysis, and the listed apnea percentage is not linked to a particular arm in the summary. Fentanyl appears in the intervention list without a described arm or posted outcome. These reporting limits constrain interpretation; they do not establish what occurred beyond the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Lusedra (Fospropofol Disodium) for Minimal to Moderate Sedation for Regional Anesthesia Block Prior to Orthopedic Surgery — NCT01195103.
• Registry record last updated 2012-06-29; status last verified 2012-06.
• Results first posted 2012-03-29.
• 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

This Phase 4 study is recorded as randomized, quadruple-masked, and parallel-group, with Mayo Clinic as sponsor. It enrolled 13 participants and is marked terminated. The registry lists arms receiving initial boluses of 10 mg/kg Lusedra, 6.5 mg/kg Lusedra, or placebo with weight-based midazolam.

The primary outcome was the percentage meeting a sedation-score threshold and having the block initiated within approximately 4 minutes after the first bolus. The posted results are 100.0% among 5 participants, 50.0% among 2 participants, and 40.0% among 5 participants, respectively. No analyses are posted, and the record does not report confidence intervals or formal comparisons. The reason for termination, missing-data handling, analysis populations, and the relationship between overall enrollment and the reported outcome group sizes are not reported in the registry record.