Clinical Trial of the Use of Intraperitoneal Local Anaesthetic: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Trial of the Use of Intraperitoneal Local Anaesthetic (NCT00180687), a randomized phase 3 study. The primary outcome is Reduction in Postoperative Pain.

2. Clinical Question

The study title describes a prospective randomized controlled trial of intraperitoneal nebulised local anaesthetic. Its registry entry includes four arm descriptions, while the brief summary describes three groups. The record does not explain this difference. Nor does it identify which comparison was designated as the main inferential contrast. Consequently, the randomized groups and planned outcome can be described, but the precise analysis question cannot be narrowed to one pairwise comparison from the registry record.

3. Trial Design

The registry identifies NCT00180687 as a completed phase 3 randomized trial sponsored by Imperial College London. The registered enrollment is 80. The start is recorded as 2004-10 and primary completion as 2005-09. The design is listed as parallel, with randomized allocation. These registry entries do not establish how many participants were ultimately randomized or analyzed.

Four arms are described: control with no intraperitoneal therapeutics; intraperitoneal aerosolized normal saline; intraperitoneal nebulised bupivacaine; and intraperitoneal injected bupivacaine. The arm descriptions specify 10 mls. For the saline and bupivacaine preparations. The brief summary says the medications were given on top of standard pain management. Further details of that standard protocol are not reported in the registry record.

The trial title uses the phrase double blind, while the registry masking entry says quadruple. The record does not define which people were masked, how masking was maintained, or whether it applied to each group in the same way. The allocation process, concealment procedures, study setting, eligibility criteria, and handling of treatment changes are not reported in the registry record.

The registry describes pain as the primary outcome and lists nausea or vomiting episodes, hours needed for safe mobilization, and postoperative morphine use as secondary outcomes. It also lists four outcome measures, but does not provide results for those secondary outcomes. The registry status is completed; completion status alone does not indicate that results were posted or that an analysis was conducted.

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

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 Reduction in Postoperative Pain, measured over 0 hours, 6 hours, 12 hours, 24 hours.

The primary endpoint is titled Reduction in Postoperative Pain. The registry describes pain measurement on a 0-10 scale, where 0 is no pain and 10 is maximum pain. Trained nursing staff were to ask patients about pain and document it in the chart. The specified assessment times are 0 hours, 6 hours, 12 hours, and 24 hours. Staff were also to record whether analgesia was required, its type, and its dose, but the registry does not state that analgesic use formed part of the primary endpoint.

Pain scores are used to represent a patient-reported symptom in a form that can be compared across randomized groups and assessment times. A group mean can describe the average recorded score, while a measure of spread can show how scores varied among participants. The registry identifies the endpoint parameter as a mean and its dispersion as the full range. It does not report the actual means, ranges, number of observations at each time, or a definition of how the repeated measurements were combined into an overall result.

The outcome has several assessment times. A score at one time answers a different question from a summary across all times, and the registry record does not specify one single time as the sole primary assessment. No pain results are reported, so the endpoint description establishes what was intended to be measured, not what the trial observed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a randomized, parallel-group design and a mean pain outcome measured at several times. It does not report the statistical methods used to analyze the trial results. The explanations below describe general statistical concepts relevant to this kind of outcome; they are not claims about analyses performed in this trial.

What does randomization contribute?

In general, random allocation is intended to make comparison groups similar, on average, with respect to both measured and unmeasured characteristics at the start of a trial. This supports interpretation of group differences as associated with assigned treatment, provided the allocation process is implemented as intended and the analysis preserves the randomized comparison. Randomization does not guarantee that groups will be identical, particularly in a modest-sized study. The registry identifies randomized allocation but does not report the sequence-generation method, concealment, or analysis population. Those details are needed to assess implementation and analysis choices.

What does a mean pain score describe?

In general, a mean is the arithmetic average of observed scores in a group at a specified assessment. It gives a compact description of the group’s central level, but by itself does not show how widely individual scores vary or whether the distribution is asymmetric. The registry states that the primary parameter is a mean and that dispersion is reported as the full range. A range describes the lowest and highest values observed, but does not show how observations are distributed between those values. No actual means or ranges are reported in the registry record.

A mean difference between groups, if reported, would express the difference in average scores on the same scale. Its interpretation would depend on the estimated magnitude, uncertainty, and clinical context. The registry record does not provide a mean difference or an analysis that compares groups. No effect estimate should be reconstructed from the descriptions alone.

Why do assessment times matter?

Repeated measurements can describe how pain changes over time, but measurements from the same participant are related rather than independent. In general, an analysis of repeated outcomes may account for this within-person association, or it may compare groups separately at specified times. Those approaches answer different questions and can yield different uncertainty estimates. The registry names assessment times at 0 hours, 6 hours, 12 hours, and 24 hours but does not report whether scores were analyzed separately, jointly, or through a summary measure.

Separate tests at multiple times and across multiple arms create multiple opportunities to find an apparently unusual result by chance. In general, multiplicity procedures can control the overall false-positive risk for a defined family of comparisons. Other approaches can designate a primary contrast or use a model that addresses the planned comparisons directly. The statistical plan, primary contrast, and any multiplicity adjustment are not reported in the registry record, so it is not possible to determine how this issue was handled.

How should uncertainty be assessed?

In general, a confidence interval describes a range of values compatible with the data under a specified statistical model and procedure. A narrow interval indicates greater precision than a wide interval, while neither interval alone establishes clinical importance. A p-value, when used, describes the compatibility of the observed data with a specified null model; it does not measure the probability that a treatment works or that the null hypothesis is true. The registry record does not report confidence intervals, p-values, standard errors, or a statistical model for the pain outcome.

When counts or scores vary more than a model assumes, over-dispersion can make standard errors too small if it is ignored. In general, an analysis can address over-dispersion through a suitable model or robust uncertainty estimates. The registry record does not report a model or distributional assessment for the pain data. This is a general consideration rather than a finding about this trial.

What do the planning assumptions mean?

The registry describes 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. It describes planning for the stated fraction of the observed effect. Such sample-size illustrations are hypothetical planning exercises, not observed power and not evidence that the trial was designed around those assumptions. The registry record does not report the calculated planning values or the underlying observed pain effect needed to interpret them. It also does not report the trial’s original sample-size justification.

Overall, the record provides design and endpoint descriptions but not an inferential analysis. In general, sound interpretation would require the group outcome summaries, an explicit comparison, an uncertainty estimate, and details about missing observations and analysis populations. These items are not reported in the registry record, so no statistical conclusion about the pain outcome can be drawn from it.

10. Multiplicity, Missing Data and Analysis Populations

The primary pain outcome is described at 0 hours, 6 hours, 12 hours, and 24 hours, and the arm descriptions list four randomized groups. Evaluating more than one time or comparison can raise multiplicity concerns. In general, if many statistical tests are conducted, the chance of at least one apparently positive result can increase unless the comparison family and approach are planned appropriately. This is a general statistical issue, not a statement that any particular number of tests was performed in this trial.

The registry record does not identify a single primary contrast among the arms, specify a primary time point, or describe a multiplicity strategy. It does not report whether the analysis used a repeated-measures model, separate comparisons by time, a planned contrast, or another approach. The statistical analysis plan and any interim analyses are not reported in the registry record. Thus, there is no basis for determining how the investigators addressed multiple possible comparisons.

Missing-data handling is also not reported. The record does not state how many participants contributed pain scores at each assessment, how missing scores were handled, or whether sensitivity analyses were conducted. It does not describe an analysis population, such as whether analyses included all randomized participants or followed another rule. The number randomized and the number analyzed for the primary endpoint are not reported in the registry record.

These omissions matter because missing outcomes and analysis choices can affect both the estimate and its uncertainty. Without the methods and outcome data, readers cannot assess whether the analysis retained the randomized comparison, whether missingness could have influenced the result, or whether conclusions were robust to reasonable alternatives. The registry’s completed status does not answer these methodological questions.

11. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events as affected participants and participants at risk for each arm. For Control, 0 serious events affected 20 at risk; for IP Aerosolized Normal Saline, 0 affected 20 at risk; for Nebulised Bupivacaine Intraperitoneally, 0 affected 20 at risk; and for Injected Bupivacaine Intraperitoneally, 0 affected 20 at risk. These are the posted serious-event counts; the registry does not list serious-event terms.

For other adverse events, the affected counts are 5 in Control, 5 in IP Aerosolized Normal Saline, 1 in Nebulised Bupivacaine Intraperitoneally, and 5 in Injected Bupivacaine Intraperitoneally. Each arm lists 20 participants at risk. The record does not describe the event types, severity, timing, or whether counts refer to participants with one or more events rather than total event episodes. Death counts are not reported in the registry record.

These entries should be read as descriptive safety counts, not as a complete comparative safety analysis. The registry does not report uncertainty estimates, statistical comparisons, follow-up details, or definitions for the adverse-event categories. The counts alone cannot establish whether groups differ in safety.

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

The record establishes that a randomized parallel-group trial was registered to study intraperitoneal local anaesthetic approaches in patients undergoing keyhole gall bladder removal. It specifies a postoperative pain scale and assessment times, lists four arm descriptions, and includes adverse-event counts. These details help define the planned research question and some of the reported safety information.

The record does not provide the primary pain results. It therefore cannot show whether mean pain scores were higher or lower in any group, whether scores changed over time, or how precise any group comparison was. It also does not report results for the listed secondary outcomes of nausea or vomiting episodes, hours needed for safe mobilization, or postoperative morphine use. The absence of posted results is not evidence that there was no difference; it means the registry record does not permit that assessment.

Nor can the adverse-event counts, by themselves, answer the primary pain question. They are separate outcomes, and their meaning is limited by the lack of event descriptions, follow-up information, and comparative uncertainty. The posted figures do not establish that one approach is safer or more hazardous than another.

More generally, a registered trial design and an outcome definition do not substitute for the results and analysis needed to interpret effects. Those results would include group summaries, the specified comparisons, uncertainty estimates, analysis methods, and information about missing observations. Without them, neither statistical significance nor clinical importance can be judged. The registry record supports a description of what was planned and which safety counts were entered, but not a conclusion about treatment effects.

13. Why This Trial Matters Statistically

This trial illustrates a basic distinction in clinical research: registration of a question is not the same as reporting its answer. The record names postoperative pain as the primary outcome and states the scale and assessment times, yet does not report the pain scores or their statistical analysis. Readers can identify the intended measurement but cannot evaluate the treatment comparisons.

The design also highlights why outcome timing and comparison structure matter. Pain was to be assessed at multiple times, and the arm descriptions include nebulised bupivacaine, injected bupivacaine, nebulised saline, and no intraperitoneal therapeutics. A clear analysis needs to say which contrasts are central and how repeated scores are handled. The registry record does not report those choices. Without them, it is difficult to know what single estimand or statistical question the trial results would address.

The safety entries offer a separate reminder about descriptive counts. Counts of affected participants are informative as a record of what was posted, but they are not a complete comparative analysis without event definitions, follow-up context, and uncertainty. The record’s serious adverse-event counts are 0 in each arm, while other adverse-event counts vary across arms. Neither pattern can be interpreted as a definitive comparison on its own.

For biostatistical reading, the trial therefore matters as an example of the limits of a registry entry: design information and outcome definitions can be useful, but effect estimates, precision, analysis populations, missing-data methods, and multiplicity handling are essential to statistical interpretation. Those elements are not reported in the registry record.

14. 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.

A major limitation for interpreting this trial from its registry record is that no primary pain results or statistical analyses are reported. The record describes the scale and assessment times, but does not provide group means, ranges, between-group estimates, confidence intervals, or p-values. The primary outcome therefore cannot be evaluated for magnitude, precision, or clinical relevance.

The record lists four arm descriptions, whereas the brief summary describes three groups. It does not explain this inconsistency or specify which comparison was primary. The trial title uses double blind wording, while the masking entry says quadruple; the record does not explain which participants or personnel were masked. These differences leave important aspects of the planned comparisons and conduct unclear.

Eligibility criteria, participant characteristics, allocation procedures, analysis populations, and the number contributing outcome data are not reported in the registry record. Missing-data methods and any sensitivity analyses are also not reported. The record does not explain how multiple assessment times or between-arm comparisons were handled. The original sample-size justification is not reported in the registry record.

The adverse-event entries provide affected counts and numbers at risk, but do not identify event types or timing. Death counts are not reported in the registry record. These limitations mean that safety counts cannot be interpreted as a comprehensive comparison. They also do not address the missing pain results. Taken together, the registry supports a description of the registered design and posted safety figures, but leaves the main efficacy question unanswered.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Clinical Trial of the Use of Intraperitoneal Local Anaesthetic — NCT00180687.
• Registry record last updated 2015-09-15; status last verified 2015-08.
• Results first posted 2015-09-15.
• 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.

18. Record Summary

NCT00180687 is a completed phase 3 randomized parallel-group trial sponsored by Imperial College London, with registered enrollment of 80. The record describes a study of intraperitoneal local anaesthetic in patients undergoing keyhole gall bladder removal, with a primary outcome of postoperative pain measured on a 0-10 scale at 0 hours, 6 hours, 12 hours, and 24 hours.

Four arm descriptions are listed: no intraperitoneal therapeutics, nebulised normal saline, nebulised bupivacaine, and injected bupivacaine. The registry also lists nausea or vomiting episodes, hours needed for safe mobilization, and postoperative morphine use as secondary outcomes. Primary pain results and statistical analyses are not reported in the registry record.

Serious adverse events affected 0 participants in each arm among 20 at risk in each arm. Other adverse events affected 5 in Control, 5 in IP Aerosolized Normal Saline, 1 in Nebulised Bupivacaine intraperitoneally, and 5 in Injected Bupivacaine intraperitoneally. Death counts are not reported in the registry record.