This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study to Determine if Carbon Dioxide Lavage During Total Knee Surgery Reduces Intraoperative Embolic Events (NCT00736125), a randomized na study. The primary outcome is The Number of Cerebral Emboli During Surgery as Measured by Transcranial Doppler (TCD).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00736125 |
| Phase | NA |
| Condition | Postoperative Complications, Memory Disorders |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 20 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Kinamed Incorporated |
| Results posted | Yes |
2. Clinical Question
Population
The registry describes a pilot study of people undergoing total knee arthroplasty. It records enrollment of 20, while the posted primary outcome and delirium outcome use different group denominators. The registry does not report participant characteristics or further eligibility details, so the population represented by the results cannot be characterized beyond the surgical setting.
Intervention
The intervention was carbon dioxide lavage using the CarboJet device to clean bone surfaces during total knee surgery. The study purpose was to assess whether use of the device was associated with fewer intraoperative embolic events than standard orthopedic techniques. The registry lists carbon dioxide lavage as a device intervention.
Comparator
The comparator was pulsatile saline lavage, described as standard orthopedic technique. The registry identifies the trial as randomized, single-masked, and parallel-group. It does not describe the allocation procedure, the identity of the masked party, or other operational details.
Primary question
The primary question concerned the number of cerebral emboli detected by transcranial Doppler during surgery. The posted count was 0 in the pulsatile saline lavage group and 3 in the carbon dioxide lavage group. Because the registry does not provide an estimable primary between-group comparison, these counts alone cannot establish the size or precision of a treatment contrast.
3. Trial Design
This was a randomized, single-masked, parallel-group pilot study comparing two lavage approaches during total knee arthroplasty. The registry lists enrollment of 20 and describes the study as completed. It lists no applicable phase. The sponsor was Kinamed Incorporated. The recorded study start was 2007-12, and primary completion was 2009-09.
The two interventions were pulsatile saline lavage and carbon dioxide lavage. The stated purpose was to determine whether carbon dioxide lavage used to clean bone surfaces during surgery was associated with fewer intraoperative embolic events than standard orthopedic techniques. The primary outcome was the number of cerebral emboli measured by transcranial Doppler during surgery. The primary outcome counts were posted for 7 participants in the saline group and 6 in the carbon dioxide group. These group denominators do not match every other posted outcome denominator, and the record does not explain the difference.
The registry also lists delirium during the first 3 days after surgery and patients with emboli in the high category as secondary outcomes. It posts numerical results for delirium, but a result for the high-category emboli outcome is not reported in the registry record. The registry describes 4 outcome measures and 2 analyses, while the available record does not explain all measures or analyses in detail.
Randomization can support a fair comparison when allocation and follow-up are properly implemented, but the record does not provide enough detail to assess these procedures. It does not report the allocation sequence method, masking details, or the reason for the group-specific denominators used for the primary endpoint. It also does not report a sample-size justification. The study is identified as a pilot, so the posted findings are best read as limited descriptive evidence rather than a precise estimate of a definitive treatment effect.
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
| Stage | 1 Pulsatile Saline Lavage | 2 Carbon Dioxide Lavage |
|---|---|---|
| STARTED | 10 | 10 |
| COMPLETED | 9 | 8 |
| NOT COMPLETED | 1 | 2 |
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.
| Characteristic | Unit | 1 Pulsatile Saline Lavage | 2 Carbon Dioxide Lavage | Total |
|---|---|---|---|---|
| Participants analysed | 10 | 10 | 20 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 6 | 6 | 12 |
| Age, Categorical: >=65 years | Participants | 4 | 4 | 8 |
| Age, Continuous | years | 62.3 (SD 3.3) | 63.9 (SD 3.7) | 63.1 (SD 3.5) |
| Sex: Female, Male: Female | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Male | Participants | 10 | 10 | 20 |
| Region of Enrollment: United States | participants | 10 | 10 | 20 |
6. Primary Endpoint
The registry lists the primary outcome as The Number of Cerebral Emboli During Surgery as Measured by Transcranial Doppler (TCD), measured over During surgery.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | emboli |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the number of cerebral emboli detected during surgery using transcranial Doppler, a monitoring method that records signals associated with embolic material moving through cerebral blood flow. The endpoint therefore represents a count of detected events during the operative period, rather than a direct measure of later memory, delirium, disability, or another clinical outcome.
Counting emboli may be useful for investigating a proposed procedural mechanism: the study asked whether cleaning bone surfaces with carbon dioxide lavage was associated with fewer intraoperative embolic events than standard orthopedic techniques. A count can capture more information than simply classifying each participant as having any embolus or none, but counts may also be unevenly distributed. Some participants may have no events while others have several. The registry does not report the distribution of individual counts, variability, or the monitoring details needed to assess how consistently events were detected.
The posted count was 0 for pulsatile saline lavage and 3 for carbon dioxide lavage. These are group-level outcome values, with 7 and 6 participants respectively listed as contributing. The record does not provide a confidence interval or an estimable primary comparison. Consequently, the counts describe the recorded results but do not quantify how uncertain the between-group contrast is. The registry also does not report the clinical importance threshold for a difference in this surrogate measure or how embolus counts relate to postoperative outcomes in this study.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary outcome was a count of cerebral emboli detected during surgery. The registry reports 0 in the pulsatile saline lavage group, with 7 participants, and 3 in the carbon dioxide lavage group, with 6 participants. These are the posted group summaries; the record does not provide an estimable two-arm comparison for this count endpoint. In particular, it does not give a standard error, confidence interval, or valid inferential test for the primary contrast. The counts therefore should not be treated as establishing the magnitude, direction, or precision of a treatment effect.
The record flags the primary count endpoint as not reduced to one comparison and notes that values are missing or not estimable for a two-arm comparison. This leaves important statistical questions unanswered: how event counts varied among participants, whether the group distributions were markedly skewed, and how the comparison was intended to account for count variability. A group count can look different even when the underlying group distributions are highly uncertain, especially in a pilot study with small outcome denominators. That is a general statistical caution, not a calculation of the trial’s result.
The secondary delirium outcome is reported for the first 3 days after surgery. The registry records 1 participant with delirium among 10 in the saline group and 4 among 10 in the carbon dioxide group. The recalculated unadjusted risk difference is 0.3, with a 95% confidence interval from -0.056 to 0.656 and an unadjusted p-value of 0.121. This interval includes no difference and is broad, spanning effects in either direction. It therefore indicates substantial uncertainty rather than a precise estimate. The registry also includes a reported two-sided t-test with p >0.05, but does not provide an estimate or confidence interval from that analysis.
The delirium figures and the primary emboli counts concern different outcomes and have different denominators. The delirium result does not fill the gap in the primary endpoint analysis, and it should not be interpreted as confirming or contradicting a primary effect on emboli. Likewise, the absence of an estimable primary comparison is not evidence that the groups were equivalent. The registry does not report a prespecified equivalence margin for the primary endpoint.
In general, confidence intervals communicate how compatible an estimate is with a range of possible underlying effects under the analysis assumptions. A wide interval means the data have limited precision. A p-value is not the probability that an intervention works or that the null hypothesis is true. Here, the available inferential result for delirium does not by itself resolve the uncertain primary comparison. The randomized design is relevant, but the small pilot scale, incomplete reporting of endpoint analyses, and unclear differences in denominators constrain interpretation.
Overall, the registry documents recorded emboli and delirium counts, but does not support a firm quantitative conclusion about the primary between-group effect. The posted material is most informative as a record of what was observed and of the limitations in the available analysis, not as a definitive estimate of the comparative effect of the two lavage approaches.
9. Statistical Methods Explained
The study is described as randomized, single-masked, and parallel-group. In a randomized study, participants are assigned to groups by chance, which is intended to reduce systematic differences between groups at the start. The registry does not report how the sequence was generated, how assignments were concealed, who was masked, or whether masking was maintained. These details matter because the label “randomized” does not by itself establish that allocation and outcome assessment were protected from bias.
How should a count endpoint be compared?
The primary outcome is a count of cerebral emboli during surgery. General statistical methods for counts include models that represent event counts and their variability. A simple count model may be unsuitable if the variability is much larger than expected under its assumptions; this is called over-dispersion. If over-dispersion is ignored, estimated uncertainty can be too small and confidence intervals or tests can be misleading. Counts can also include many zeros or a small number of high values, making the shape of the data important. These are general considerations, not claims about the distribution in this trial: the registry does not report participant-level counts, dispersion, or a primary model.
The posted primary group values are 0 and 3, but a comparison requires more than those two summaries to estimate uncertainty reliably. The group denominators are 7 and 6, and the registry marks a two-arm comparison as missing or not estimable. It does not report the analysis method that would have been used for this endpoint, an adjusted estimate, or a confidence interval. No recalculated primary contrast is available in the registry record.
What does the delirium analysis report?
For delirium during the first 3 days after surgery, the registry reports 1 participant with the outcome among 10 in the pulsatile saline group and 4 among 10 in the carbon dioxide group. A recalculated unadjusted risk difference is 0.3, with a 95% confidence interval from -0.056 to 0.656. The unadjusted p-value is 0.121. These recalculations use the posted summary counts and are not adjusted for other variables or for multiple outcomes.
A risk difference expresses the difference between group risks on an absolute scale. A confidence interval gives a range of values compatible with the estimate under the method’s assumptions; an interval that includes no difference does not establish that the groups are identical. Here, the broad interval reflects imprecision. The registry also reports a two-sided t-test with p >0.05, but its estimate, confidence interval, and test parameter are not reported in the registry record. The posted analysis method should therefore be distinguished from the unadjusted recalculation, which answers a simple comparison based on the listed counts.
How should the planning illustrations be read?
The planning illustrations use the observed delirium effect as a starting point and consider planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. They report participants per arm for 80% power and participants per arm for 90% power. Under the stated planning assumptions, the figures are 32 and 42 for 100% of the observed effect; 51 and 68 for 75% of the observed effect; and 100 and 133 for 50% of the observed effect, respectively.
These are planning illustrations, not observed power and not the trial’s original sample-size justification. They assume a two-sided significance level of 0.05, equal allocation, and a normal approximation. They illustrate that planning to detect a smaller effect generally requires a larger sample, all else equal. They do not show that a future study would achieve the stated power if its assumptions were wrong, and they do not establish that the observed effect is a reliable estimate of the effect to plan around. The registry does not report its own sample-size assumptions or justification.
What is the role of p-values and confidence intervals?
A p-value describes how unusual data at least as incompatible with a null hypothesis would be under the test assumptions; it is not a measure of effect size or a probability that a hypothesis is true. A confidence interval gives information about uncertainty and a range of effects compatible with the data and analysis. Neither can repair limitations in the underlying data, such as incomplete outcome reporting or unclear analysis populations. For the primary endpoint, the necessary inferential quantities are not reported. For delirium, the unadjusted estimate and interval show considerable uncertainty.
The registry’s secondary outcomes should also be interpreted in light of multiple testing. When several outcomes are examined, the chance of at least one apparently unusual result can increase if each is assessed separately without adjustment. The registry does not report a multiplicity strategy. That does not mean every secondary finding is false; it means unadjusted findings are less conclusive and are appropriately treated as exploratory, particularly in a small pilot study.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple outcomes, including the primary count of cerebral emboli during surgery and secondary outcomes concerning high-category emboli and delirium. It reports 4 outcome measures and 2 analyses, but the available record does not give complete results for every listed measure. In particular, the high-category emboli result is not reported in the registry record. The record also does not describe a prespecified hierarchy among outcomes or a multiplicity adjustment procedure.
When several outcomes are tested separately, the chance of an apparently notable result can increase. General approaches include specifying one primary endpoint, controlling error across a defined family of tests, or treating secondary analyses as exploratory. The registry record does not report which approach, if any, was planned. The delirium p-value is unadjusted, so it should not be read as if it accounted for examining other outcomes.
Missingness and analysis populations are also important. The registry reports the primary count for 7 participants in the saline group and 6 in the carbon dioxide group, while the delirium and adverse-event figures use 10 participants in each group. Enrollment is listed as 20. The record does not explain these different denominators or state whether they reflect missing measurements, exclusions, availability of monitoring, or different analysis populations. None of those explanations should be assumed.
The registry does not report participant flow, reasons for missing outcomes, imputation methods, or whether analyses followed the randomized assignment regardless of treatment received. It therefore is not possible to assess whether missing primary measurements could have affected the comparison. The record also does not report a sample-size justification or a detailed statistical analysis plan. These gaps limit evaluation of outcome selection, analysis choices, and the robustness of the posted results.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| 1 Pulsatile Saline Lavage | 0 | 10 | 0.0% |
| 2 Carbon Dioxide Lavage | 0 | 10 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| 1 Pulsatile Saline Lavage | 0 of 10 |
| 2 Carbon Dioxide Lavage | 0 of 10 |
The adverse-event record reports 0 serious adverse events among 10 participants in the pulsatile saline lavage group and 0 among 10 participants in the carbon dioxide lavage group. It also reports 0 other adverse events among 10 participants in each group. Deaths are not reported in the registry record. No serious adverse-event terms are listed.
These figures describe the events recorded in the registry; they do not establish that no adverse events occurred beyond the reporting period or outside the definitions used. The record does not provide event definitions, ascertainment procedures, follow-up duration for safety, or detailed participant-level information. The denominators for the safety figures also differ from those posted for the primary outcome, and the reason is not reported.
Zero recorded events in these groups should not be interpreted as evidence that the interventions have identical safety profiles. Small amounts of safety data provide limited ability to detect uncommon events or differences between groups. The figures are a description of the posted safety experience, not a comparative safety estimate with a reported confidence interval.
12. What the Result Does, and Does Not, Mean
The record shows that cerebral emboli were counted during surgery by transcranial Doppler, with a posted group value of 0 for pulsatile saline lavage and 3 for carbon dioxide lavage. It also shows a delirium outcome comparison with a recalculated unadjusted risk difference of 0.3 and a broad 95% confidence interval from -0.056 to 0.656. Those observations are informative as descriptions of the recorded data, but their precision and completeness differ.
The primary endpoint lacks an estimable between-group comparison in the registry record. It is therefore not possible to use the posted counts to make a reliable quantitative statement about the size or precision of the primary effect. The counts are not a direct measure of postoperative memory or delirium, and the registry does not report an analysis connecting emboli counts to later outcomes. The secondary delirium result is also uncertain and does not resolve the primary analysis gap.
These findings do not establish that either lavage approach reduces emboli, nor do they establish that the approaches are equivalent. A result that is not statistically significant is not proof of no effect, and a missing primary comparison is not a negative finding. The registry does not report an equivalence margin or a complete primary analysis that would support an equivalence conclusion.
In general, a pilot study can offer preliminary descriptive information and help identify practical or analytic questions for later research. It cannot by itself guarantee that an observed effect will recur or that a future study will reach the same conclusion. Here, group denominators vary across outcomes and the record does not explain why. This further limits the interpretation of the posted results.
The appropriate reading is cautious: the registry documents a randomized pilot comparison and several recorded outcomes, but it does not provide a precise, complete primary estimate. Any interpretation should distinguish observed counts from inferential evidence and recognize that the available secondary analysis is unadjusted and imprecise.
13. Why This Trial Matters Statistically
This trial illustrates an important distinction between reporting an outcome value and reporting a usable comparative estimate. For the primary endpoint, the registry gives group counts but marks a two-arm comparison as missing or not estimable. Without an estimate of uncertainty, readers cannot judge how compatible the observed counts are with a range of possible underlying group effects.
It also shows why the form of an endpoint matters. Cerebral emboli are reported as counts, which may be distributed unevenly among participants. Appropriate statistical analysis needs to account for the count distribution and its variability. A simple comparison based only on group-level values cannot reveal whether events were spread across participants or concentrated in a few. The registry does not report the information needed to assess that distribution.
The differing denominators across the primary endpoint, delirium, and adverse-event summaries are another useful reporting lesson. Without participant flow and reasons for unavailable measurements, readers cannot determine which analysis populations contributed to each result. Clear accounting of outcomes and denominators is essential to assess possible bias and the scope of each estimate.
Finally, the registry illustrates the difference between exploratory secondary analyses and a well-specified primary analysis. The delirium estimate is available but imprecise, while the primary comparison is not estimable in the record. Unadjusted secondary results can be useful for describing patterns, but they should not be treated as decisive when multiple outcomes are considered and a multiplicity strategy is not reported. Together, these features make transparent analysis plans, complete outcome reporting, and precise uncertainty estimates central to interpreting small clinical trials.
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.
The most direct limitation is that the registry does not provide an estimable primary between-group comparison for the cerebral emboli count. The group values alone do not show the uncertainty around a contrast. The record also does not report individual-level count distributions, a measure of variability, or the primary statistical model, limiting assessment of whether the analysis appropriately handled count data.
The posted denominators vary by outcome. The primary endpoint uses 7 and 6 participants, whereas delirium and adverse-event reporting use 10 participants per group. The registry does not explain these differences. It also does not report participant flow, missing-data reasons, or analysis-population definitions. This prevents readers from determining whether the outcome groups represent comparable populations.
The registry does not report allocation-sequence generation, concealment, masking details, baseline characteristics, or a detailed protocol and statistical analysis plan. It is therefore not possible to assess how randomization and masking were implemented, whether the endpoint analyses followed prespecified methods, or whether relevant differences between groups were addressed.
The trial is described as a pilot and has limited posted outcome denominators. The delirium comparison is imprecise, and its reported unadjusted result does not account for multiple outcomes. A result for the high-category emboli secondary outcome is not reported in the registry record. The record also does not report a sample-size justification, a primary equivalence margin, or complete safety follow-up details.
These limitations concern the information available in the registry record; they do not establish that unreported procedures or analyses were not performed. They do mean that the posted information is insufficient for a robust, precise interpretation of the primary comparative effect.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Determine if Carbon Dioxide Lavage During Total Knee Surgery Reduces Intraoperative Embolic Events — NCT00736125.
- Registry record last updated 2019-09-26; status last verified 2019-09.
- Results first posted 2013-04-18.
- 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.
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18. Record Summary
The record describes a completed randomized, single-masked, parallel-group pilot study sponsored by Kinamed Incorporated. The study compared carbon dioxide lavage with pulsatile saline lavage during total knee arthroplasty. Enrollment was 20; the recorded study start was 2007-12 and primary completion was 2009-09.
The primary endpoint was the number of cerebral emboli measured by transcranial Doppler during surgery. The posted values were 0 among 7 participants receiving pulsatile saline lavage and 3 among 6 receiving carbon dioxide lavage. The registry does not provide an estimable primary comparison or its uncertainty.
For delirium during the first 3 days after surgery, the posted counts were 1 of 10 and 4 of 10. The unadjusted recalculated risk difference was 0.3, with a 95% confidence interval from -0.056 to 0.656. The safety record lists no serious or other adverse events in either group; deaths are not reported in the registry record. The record does not explain differing denominators, report all listed outcome results, or provide a detailed statistical plan.