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 Dexmedetomidine Versus Midazolam for Facilitating Extubation (NCT00744380), a randomized na study. The primary outcome is Time From Study Drug Initiation to Tracheal Extubation.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00744380 |
| Phase | NA |
| Condition | Critical Illness |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 23 |
| Arms in the primary outcome | 2 |
| Lead sponsor | University of Colorado, Denver |
| Results posted | Yes |
2. Clinical Question
Population
Medical or surgical intensive care unit patients requiring sedation while tracheal extubation was nearing. The registry summary describes patients receiving existing benzodiazepine therapy who qualified for daily awakenings. The primary endpoint analysis was restricted to patients successfully extubated for at least 72 hours; the record states that eight subjects were excluded from that analysis.
Intervention
Dexmedetomidine was administered by infusion, beginning at 0.15 µg/kg per hour and adjusted by 0.15 µg/kg per hour as needed for the target sedation level while other sedatives were down titrated. Daily awakenings were used.
Comparator
Midazolam was administered by infusion, beginning at 1 mg/hour and adjusted by 1 mg/hour as needed for the target sedation level while other sedatives were down titrated. Daily awakenings were used.
Primary question
How did the time from study-drug initiation to tracheal extubation compare between the dexmedetomidine and midazolam groups? The registry reports median times and a Wilcoxon (Mann-Whitney) comparison. The recorded p-value is 0.8. This result concerns the posted endpoint and analysis population; it does not by itself establish equivalence or answer every question about sedation, safety, cost, or later experiences.
3. Trial Design
The registry describes a randomized, double-blind, parallel-group study comparing dexmedetomidine with midazolam in medical and surgical ICU patients. Masking is recorded as quadruple. The registry record does not explain which study roles were masked or how masking was maintained. The study is listed as completed, with phase recorded as not applicable. The sponsor was the University of Colorado, Denver.
The registry’s brief summary describes a planned study of 50 patients requiring sedation with existing benzodiazepine therapy and qualifying for daily awakenings. The recorded enrollment is 23. The record does not explain why enrollment was lower than the number described in the summary, or whether the intended enrollment changed. A sample-size justification is not reported in the registry record.
Both groups received study-drug infusions while other sedatives were down titrated, with daily awakenings. The stated target was a Riker sedation-agitation score of 3 - 4. The midazolam infusion began at 1 mg/hour, with adjustments of 1 mg/hour; the dexmedetomidine infusion began at 0.15 µg/kg per hour, with adjustments of 0.15 µg/kg per hour. The registry also describes final infusion concentrations for each drug. These are protocol descriptions, not evidence about how consistently treatment was delivered to individual participants.
The primary endpoint was time from study-drug initiation to tracheal extubation. The registry lists several secondary topics, including sedative and analgesic doses, sedation and analgesia assessments, adverse effects, ICU experiences, study-drug duration, acute stress symptoms, and anxiety and depression scores. Results for every planned or listed outcome are not necessarily available in the record. The registry does not report the detailed randomization procedure, allocation concealment, adherence, or protocol deviations.
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 | Midazolam | Dexmedetomidine |
|---|---|---|
| STARTED | 12 | 11 |
| COMPLETED | 12 | 11 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: The analysis only includes patients successfully extubated for at least 72 hours. Eight subjects were excluded.
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 | Midazolam | Dexmedetomidine | Total |
|---|---|---|---|---|
| Participants analysed | 12 | 11 | 23 | |
| Age, Continuous | years | 57.8 (SD 9.3) | 58.3 (SD 15.3) | 58.1 (SD 13.5) |
| Sex: Female, Male: Female | Participants | 5 | 5 | 10 |
| Sex: Female, Male: Male | Participants | 7 | 6 | 13 |
| Weight | kg | 105.2 (SD 40.9) | 100.8 (SD 37.4) | 103 (SD 38.5) |
| Acute Physiologic And Chronic Health Evaluation III Score | units on a scale | 70.4 (SD 33.5) | 74.1 (SD 18.2) | 72.8 (SD 25) |
| Primary Diagnosis: Respiratory failure | participants | 5 | 5 | 10 |
| Primary Diagnosis: Sepsis | participants | 5 | 4 | 9 |
| Primary Diagnosis: Other | participants | 2 | 2 | 4 |
| Time in ICU before qualifying | days | 1.1 (0.6 to 2) | 1.2 (0.9 to 5.4) | 1.1 (0.6 to 5.4) |
| Time from qualifying to randomization | days | 1 (0.7 to 1.1) | 0.7 (0.5 to 0.8) | 0.9 (0.5 to 1.1) |
| Baseline Sedative: Midazolam | participants | 10 | 6 | 16 |
| Baseline Sedative: Lorazepam | participants | 2 | 5 | 7 |
6. Primary Endpoint
The registry lists the primary outcome as Time From Study Drug Initiation to Tracheal Extubation, measured over Duration of ICU stay, for up to 24 weeks.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | days |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint measures elapsed time from initiation of the assigned study drug until tracheal extubation. It is a time-to-event outcome: the event of interest is extubation, and the recorded measure describes when that event occurred. Such an endpoint can capture timing rather than simply whether an event occurred, which may be relevant when evaluating a transition in sedation near extubation.
The registry reports the endpoint as a median in days, with interquartile range as the stated measure of dispersion. The midazolam group’s median was 2.9 days, with interquartile limits of 2.0 and 4.4 days. The dexmedetomidine group’s median was 3.4 days, with interquartile limits of 2.6 and 14.2 days. These summaries describe the observed endpoint in each analysis group; they do not show the individual participants’ event times or explain the shape of the underlying distributions.
The analysis population is limited to patients successfully extubated for at least 72 hours. The registry says eight subjects were excluded. This restriction is important: the reported medians do not represent all enrolled patients under an analysis that retains every randomized participant. The registry does not report how participants who were not successfully extubated for that duration were handled beyond the stated exclusion, nor does it provide a separate endpoint result for them.
Although time-to-event methods can account for censoring when event times are not observed, the posted primary comparison is identified as a Wilcoxon (Mann-Whitney) test. A detailed account of censoring or the rationale for this test is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted median time from study-drug initiation to extubation was 2.9 days for midazolam and 3.4 days for dexmedetomidine. The interquartile limits were 2.0 and 4.4 days for midazolam, and 2.6 and 14.2 days for dexmedetomidine. The registry reports a Wilcoxon (Mann-Whitney) p-value of 0.8 for the comparison.
A p-value of 0.8 indicates that the reported test did not identify a statistically notable separation between the groups under its null hypothesis. It is not the probability that the treatments are identical, and it does not establish equivalence. The result should be read alongside the group summaries, analysis population, and limited enrollment. It does not prove that clinically relevant differences are absent.
The endpoint distributions are described by medians and interquartile limits rather than means and standard deviations. The upper interquartile limit for dexmedetomidine is 14.2 days, compared with 4.4 days for midazolam. That difference in the reported spread signals that the middle portion of the observed values was less compact in the dexmedetomidine group. It does not, on its own, explain why those times were distributed that way or establish a cause.
The comparison includes patients successfully extubated for at least 72 hours, and eight subjects were excluded from this analysis. The result therefore answers a narrower question than an analysis that included all randomized patients. The registry does not report enough detail to determine how the exclusions affected comparability between groups, or whether the exclusions were specified before the results were known.
The study’s recorded enrollment was 23, while the registry summary described a planned study of 50 patients. That context matters when interpreting a non-significant result: limited data can leave considerable uncertainty even when a test does not flag a difference. The record provides no confidence interval for the group contrast, so the precision of a direct treatment-effect estimate cannot be assessed from the reported comparison. Interquartile limits describe the distribution within each group; they are not a confidence interval for the difference between groups.
The posted result concerns time to extubation in this analysis population. It does not by itself resolve the secondary questions about sedative use, sedation quality, analgesia, adverse effects, ICU experiences, or later psychological measures. Nor does the primary comparison alone establish effects on cost or overall safety. Those conclusions would require the relevant outcome results and their analysis details.
9. Statistical Methods Explained
The primary endpoint is summarized with a median and interquartile range. The median is the central value when observations are ordered. The interquartile range describes the middle half of the observed values, using its lower and upper quartile limits. These summaries are often useful when data are skewed or have unusually large values, because the median is less influenced by extreme observations than the mean. General explanation: medians and quartiles describe the observed distribution; they do not directly quantify uncertainty about a treatment contrast.
What does the Wilcoxon (Mann-Whitney) test compare?
The registry identifies the primary comparison as a Wilcoxon (Mann-Whitney) test. In general, this rank-based test compares the ordering of observations between groups rather than relying on a comparison of group means under a normal-distribution assumption. It can be useful for outcomes whose distributions are skewed. Its interpretation is not automatically a test of medians alone: differences in distributional shape can also influence the result. The registry does not report a fuller statistical analysis plan or explain the choice of this test for the time-to-extubation endpoint.
The posted p-value is 0.8. In general, a p-value describes how compatible the observed test result is with a specified null model, assuming that model and the test assumptions hold. It is not a measure of the size or clinical importance of a difference. It is also not the probability that the null hypothesis is true. No confidence interval for a between-group effect is reported, so the p-value should not be treated as a substitute for an interval describing the plausible range of that effect.
How should the endpoint’s time-to-event nature be considered?
Time to extubation is a time-to-event outcome because it records elapsed time until a defined event. General explanation: time-to-event analyses may need to address censoring, which occurs when the event time is not observed during the available follow-up. Methods such as survival models can incorporate censoring under stated assumptions. The registry reports a Wilcoxon (Mann-Whitney) test and medians, but does not report a censoring method, a hazard ratio, or a detailed time-to-event model for this primary comparison. The registry record therefore does not support describing the result as a hazard-ratio analysis.
The endpoint timeframe is listed as duration of ICU stay, for up to 24 weeks. The primary analysis population is described as patients successfully extubated for at least 72 hours, with eight subjects excluded. This restriction affects what the analysis estimates: it is a comparison among those meeting the stated extubation criterion, not a full randomized-population analysis. The record does not describe how the exclusion rule was applied in practice, or whether the analysis was planned before unblinding.
Can the group summaries reproduce the reported comparison?
The medians and quartile limits are not enough to reconstruct the individual rankings used by a Wilcoxon (Mann-Whitney) test. Many different sets of participant-level observations can share the same median and quartiles while producing different rank-test results. The registry also marks a two-arm recalculation as not estimable for this median-time endpoint. Accordingly, no unadjusted recalculated test statistic, p-value, or confidence interval should be inferred from the summaries.
General explanation: over-dispersion means that variability is greater than a model expects. If a model assumes more uniform or less variable observations than are actually present, its uncertainty estimates can be too small and its statistical conclusions misleading. Here, the available registry entries do not establish that a particular over-dispersion problem occurred, and no model-based variance estimate is reported. This is a general consideration rather than a finding about this trial.
What do planning illustrations represent?
Any sample-size illustration based on an observed effect is a planning exercise, not a measure of the trial’s observed power. The registry’s stated illustration assumptions include a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the target effect is described as a stated fraction of the observed effect. General explanation: such calculations ask how much information a future study might need under chosen assumptions. They do not show the probability that this completed study detected an effect, and they do not replace a documented design justification. The sample-size justification for this trial is not reported in the registry record.
The record lists multiple outcomes and analyses, but does not describe an adjustment for multiple comparisons, an interim analysis, a prespecified hierarchy among outcomes, or a complete statistical analysis plan. These omissions limit assessment of how the primary comparison was selected and how other analyses should be interpreted.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| Wilcoxon (Mann-Whitney) | not reported | 0.800 |
The sponsor-reported primary comparison is a Wilcoxon (Mann-Whitney) test with p = 0.8. It accompanies the reported medians and interquartile limits for the two groups. Because the endpoint is summarized by group medians and quartiles, those summary values do not contain the participant-level ranks needed to reproduce the sponsor’s test.
The registry record marks a two-arm recalculation as not estimable for this median-time endpoint. No recalculated p-value or effect interval is therefore reported. This is not a case in which a recalculated result conflicts with the sponsor’s analysis; the posted summaries do not permit that direct unadjusted recalculation. The sponsor’s reported analysis remains the available inferential comparison in the registry.
The p-value should not be read as evidence that the groups are equivalent. It indicates that the reported test did not identify a statistically notable difference under its null hypothesis. The record does not report a confidence interval for a between-group effect, so readers cannot use the posted result to assess the precision of such an estimate. The distinction matters: the absence of a recalculated contrast is not proof of no effect, and the sponsor’s p-value does not express the probability that the groups are identical.
11. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary time-to-extubation outcome along with secondary outcomes covering sedative and analgesic doses, sedation and analgesia assessments, sedation-related adverse effects, ICU experiences, study-drug duration, acute stress symptoms, and anxiety and depression scores. It also records 15 analyses and 8 outcome measures. The record does not explain how those analyses were organized, which comparisons were prespecified, or whether any inferential results were adjusted for multiple testing.
When several outcomes or comparisons are examined, the chance of finding at least one apparently unusual result can increase. General explanation: multiplicity procedures or a prespecified outcome hierarchy can help control how multiple statistical tests are interpreted. The registry does not report such procedures, so the status of adjustment is not reported in the registry record. This uncertainty is especially relevant to secondary findings; it does not change the meaning of the sponsor’s reported primary p-value but does limit a complete assessment of the wider set of analyses.
The primary analysis excludes patients who were not successfully extubated for at least 72 hours, and the record states that eight subjects were excluded. It does not provide a detailed participant flow, the reasons for each exclusion, or a comparison of excluded patients by randomized group. The registry also does not describe a missing-data strategy, an intention-to-treat analysis, a per-protocol analysis, or sensitivity analyses. These details are not reported in the registry record.
Without those details, it is not possible to assess fully whether exclusions or missing outcome information could have influenced the endpoint comparison. The reported medians and test therefore apply to the stated analysis population, rather than necessarily representing the outcomes of every randomized participant. An interim analysis plan and stopping rules are also not reported in the registry record.
12. 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 |
|---|---|---|---|
| Midazolam | 0 | 12 | 0.0% |
| Dexmedetomidine | 1 | 11 | 9.1% |
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 |
|---|---|
| Midazolam | 12 of 12 |
| Dexmedetomidine | 11 of 11 |
Most frequent serious adverse event terms
| Event term | Organ system | Midazolam | Dexmedetomidine |
|---|---|---|---|
| Acute Neurologic Encephalopathy | Nervous system disorders | 0 of 12 | 1 of 11 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Midazolam | Dexmedetomidine |
|---|---|---|---|
| Hypotension | Cardiac disorders | 6 of 12 | 10 of 11 |
| Bradycardia | Cardiac disorders | 7 of 12 | 7 of 11 |
| Tachycardia | Cardiac disorders | 5 of 12 | 7 of 11 |
| Delirium, new onset | Nervous system disorders | 5 of 12 | 5 of 11 |
Serious events with the highest arm-level rate: acute neurologic encephalopathy (9.1%).
The adverse-event record reports serious adverse events for 0 of 12 participants at risk in the midazolam group and 1 of 11 participants at risk in the dexmedetomidine group. The registry also lists other adverse events affecting 12 of 12 participants at risk in the midazolam group and 11 of 11 participants at risk in the dexmedetomidine group. These are the posted event counts and denominators; they should not be combined with the primary endpoint analysis population, which has different group sizes.
Acute Neurologic Encephalopathy is listed among the top serious adverse-event terms, with 9.1% recorded. The registry does not give enough detail in this record to establish how that term relates to the single serious adverse event in the dexmedetomidine group or to describe participant-level event histories. Deaths are not reported in the adverse-event fields.
These counts describe reported events in the recorded safety groups. They do not establish that an event was caused by study treatment, and the record does not provide a detailed assessment of causality or severity beyond the serious-event classification. With the available information, comparisons of safety should remain descriptive rather than interpreted as definitive evidence of a difference between treatments.
13. What the Result Does, and Does Not, Mean
The result reports median time from study-drug initiation to tracheal extubation of 2.9 days with midazolam and 3.4 days with dexmedetomidine, with a Wilcoxon (Mann-Whitney) p-value of 0.8. The interquartile limits indicate the spread of observed times within each group. This is the statistical finding in the registry for the primary endpoint and stated analysis population.
The finding does not establish equivalence, prove that no difference exists, or show that either drug is preferable. A non-significant p-value is not an equivalence test. The registry does not report an equivalence margin, a confidence interval for the between-group effect, or a formal non-inferiority or equivalence analysis. Precision of the treatment contrast therefore cannot be judged from the reported p-value alone.
The primary analysis includes patients successfully extubated for at least 72 hours, and eight subjects were excluded. The result consequently does not answer the same question as a complete analysis of all randomized participants. The reason for each exclusion and the effect of those exclusions on the comparison are not reported in the registry record.
The result also does not settle the study’s other questions. The registry lists secondary outcomes related to medication use, sedation quality, analgesia, adverse effects, ICU experiences, and later symptoms. Those outcomes require their own reported results and methods. The primary endpoint comparison does not establish a conclusion about cost, and the serious adverse-event counts alone do not establish a causal safety difference.
Finally, the registry reports enrollment of 23, while its summary describes a planned study of 50. The record does not report a sample-size justification. The study should therefore be interpreted as a limited dataset with important uncertainties, not as a definitive assessment of all potential differences between the study drugs.
14. Why This Trial Matters Statistically
This trial illustrates why a clinical comparison cannot be reduced to a single p-value. The primary outcome is a time measure summarized by medians and interquartile limits, and the reported inferential test is rank based. Those choices give different information: the group summaries describe observed distributions, while the p-value summarizes the result of a statistical comparison under its assumptions.
It also highlights the importance of the analysis population. The posted endpoint comparison is restricted to participants successfully extubated for at least 72 hours, with eight subjects excluded. Readers need that qualification to understand who contributes to the result and what population it describes. Without a detailed account of exclusions or a full randomized-population analysis, the scope of the finding remains limited.
The difference between planned and recorded enrollment is another useful statistical lesson. The registry summary describes a planned study of 50 patients, while recorded enrollment is 23. Without a documented sample-size justification or explanation of the enrollment change, readers cannot determine what precision the investigators intended or why enrollment ended at the recorded level. Non-significance in this context should not be mistaken for proof of no meaningful difference.
Finally, the record shows the value of reporting complete methods alongside results. Details about missing outcomes, multiplicity, censoring, and analysis populations would help readers assess reliability and uncertainty. Where those details are not reported, careful interpretation means describing the posted result narrowly and leaving unsupported conclusions open.
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 primary endpoint analysis does not include everyone enrolled. The registry states that it includes only patients successfully extubated for at least 72 hours and that eight subjects were excluded. Reasons for exclusion, timing of exclusions, and group-specific details are not reported in the registry record. This limits evaluation of whether the analyzed groups remained comparable after randomization.
Recorded enrollment was 23, whereas the brief summary describes a plan to randomize 50 patients. The record does not explain the difference or report the sample-size justification. This makes it difficult to assess the intended precision of the primary comparison. The reported p-value of 0.8 does not provide a confidence interval, and the group summaries cannot reconstruct one.
The registry identifies a Wilcoxon (Mann-Whitney) comparison but does not report the full statistical analysis plan, details of handling censoring, or participant-level data. The reasons for selecting this comparison and its assumptions are therefore not fully assessable. The record also does not report how missing observations were handled, whether an intention-to-treat analysis was conducted, or whether sensitivity analyses were performed.
Multiple secondary outcomes and analyses are listed, but procedures for multiplicity, outcome hierarchy, or interim analyses are not reported. The record does not provide enough detail to assess the reliability of every secondary finding. Safety information is also limited to the reported event counts and terms; deaths are not reported in the adverse-event fields, and detailed causal assessments are unavailable.
These limitations do not invalidate the recorded summaries. They define what can be inferred from them: a sponsor-reported comparison for a restricted analysis population, with substantial gaps in the record about precision, exclusions, and analysis choices.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Dexmedetomidine Versus Midazolam for Facilitating Extubation — NCT00744380.
- Registry record last updated 2016-09-28; status last verified 2016-08.
- Results first posted 2016-09-28.
- 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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19. Record Summary
The registry describes a randomized, double-blind, parallel-group comparison of midazolam and dexmedetomidine in medical and surgical ICU patients approaching extubation. The study is listed as completed, with recorded enrollment of 23. Its primary endpoint is time from study-drug initiation to tracheal extubation, analyzed among patients successfully extubated for at least 72 hours.
The reported median times were 2.9 days for midazolam and 3.4 days for dexmedetomidine. The sponsor-reported Wilcoxon (Mann-Whitney) comparison had p = 0.8. Eight subjects were excluded from the primary analysis. The registry does not report a confidence interval for the between-group effect or a detailed account of exclusions, missing data, or multiplicity methods.
The record also lists secondary outcomes and adverse-event counts. The primary result should be read as a limited comparison within its stated analysis population, not as proof of equivalence or a complete assessment of safety and other outcomes.