Safety, Efficacy and Pharmacokinetic Study of Dexmedetomidine in Pediatrics Ages ≥28 Weeks to ≤44 Weeks Gestational Age: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Efficacy and Pharmacokinetic Study of Dexmedetomidine in Pediatrics Ages ≥28 Weeks to ≤44 Weeks Gestational Age (NCT01159262), a non-randomized phase 2, phase 3 study. The primary outcome is Percentage of Subjects Who Received Rescue Medication Midazolam for Sedation During Dexmedetomidine Infusion.

2. Clinical Question

In general, comparing rescue medication use across dose groups can describe whether additional medication was used under the study conditions. It does not by itself show why rescue was given or establish that dose caused any difference. Interpretation also depends on how rescue use was defined, how clinicians decided to administer it, and how missing observations were handled. Those details are not reported in the registry record.

3. Trial Design

The registry record describes a Phase II/III, open-label, multicenter, parallel study of dexmedetomidine in neonates from 28 to 44 weeks gestational age. The study is marked completed, with enrollment listed as 36. Its stated purpose was to investigate safety, efficacy, and pharmacokinetics at three dexmedetomidine dose levels. Administration was described as a loading dose followed by continuous infusion for at least 6 hours and up to 24 hours in a neonatal intensive care unit, cardiac intensive care unit, or pediatric intensive care unit.

Allocation is recorded as non-randomized and masking as none. The three arm descriptions specify dexmedetomidine loading and maintenance doses of 0.05 mcg/kg and 0.05 mcg/kg/hr, 0.1 mcg/kg and 0.1 mcg/kg/hr, and 0.2 mcg/kg and 0.2 mcg/kg/hr. Midazolam and fentanyl/morphine are listed as drug interventions; midazolam and opioid rescue use are also addressed by secondary outcomes. The registry record does not describe a separate control arm or explain how participants were assigned to dose levels.

The record identifies a study start of 2010-07 and primary completion of 2011-08. The sponsor is listed as Hospira, now a wholly owned subsidiary of Pfizer. Because this was non-randomized and unmasked, dose-group differences should be read as descriptive comparisons, not as randomized estimates of a dose effect. Non-random assignment can leave measured or unmeasured group characteristics uneven, while lack of masking can affect decisions about rescue medication or assessment. The registry record does not report methods intended to address such differences.

There is an internal wording inconsistency relevant to design interpretation: allocation is marked non-randomized, while the efficacy-evaluable population description refers to subjects who received “randomized Dexmedetomidine.” The registry record does not resolve that conflict. It also does not report the intended allocation mechanism, the number enrolled in each arm as an enrollment figure, or whether participants could move between dose levels.

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

Analysis population for the primary outcome, as defined in the registry: Efficacy Evaluable Population: All subjects who received randomized Dexmedetomidine for at least 6 hours.

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 Subjects Who Received Rescue Medication Midazolam for Sedation During Dexmedetomidine Infusion, measured over During study drug administration (6 to 24 hours).

The primary endpoint is the percentage of subjects who received rescue midazolam for sedation during dexmedetomidine infusion. Its stated timeframe is during study drug administration, from 6 to 24 hours. The efficacy-evaluable population is described as all subjects who received dexmedetomidine for at least 6 hours, although the population description also uses the conflicting word “randomized.”

This is a binary outcome at the participant level: for each subject, the endpoint concerns whether rescue midazolam was received during the specified period. A percentage expresses the number of subjects with the event relative to the eligible population. The registry record gives the endpoint definition but does not report its event count, denominator, percentage, or uncertainty interval.

In general, rescue medication use can be a pragmatic measure of additional medication needed during a treatment period. It may be useful alongside other measures because it captures a treatment decision that occurred in clinical care. However, it is not equivalent to a direct measure of sedation quality, and it does not explain the reason for rescue use. Clinician thresholds, local practice, and opportunity to observe an event can affect this endpoint. The record does not provide a detailed rescue-medication protocol or criteria for administration, so those influences cannot be assessed.

Midazolam is specified for the primary sedation endpoint; rescue medication for analgesia and other medication amounts are listed among secondary outcomes. Those outcomes address different questions and should not be substituted for the primary endpoint. Without the posted primary result, no claim about the frequency of rescue midazolam use or differences across dose groups can be made.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary because it records whether a subject received rescue midazolam during the defined infusion period. The registry record describes the outcome as a percentage of subjects and identifies its parameter as a number of subjects. In general, a binary outcome is summarized by an event count and a denominator, from which a proportion or percentage is obtained. Those components are essential for understanding both the observed frequency and its precision. Neither the event count nor the primary denominator is reported in the registry record.

What does a percentage describe?

In general, a percentage represents the share of eligible observations with the event of interest. For this endpoint, the event is receipt of rescue midazolam for sedation during dexmedetomidine administration. A percentage does not describe the amount of midazolam, the timing of each dose, or the reason for rescue. Those are separate questions. The registry record lists total rescue-medication amounts among secondary outcomes, but does not report those values or explain how the primary event was operationally classified.

For a useful estimate, the denominator should correspond to the population specified for analysis. Here the efficacy-evaluable definition is subjects receiving dexmedetomidine for at least 6 hours. The record does not give the number who satisfied that definition, whether all eligible subjects had outcome data, or how participants with incomplete observation were treated. A percentage without a clear denominator can be difficult to compare across groups or studies.

Why does uncertainty matter?

In general, a point estimate is only one description of a sample. A confidence interval conveys uncertainty around that estimate under a specified statistical method. Wider intervals indicate less precision, while narrower intervals indicate greater precision, but the interval does not address bias from non-random allocation or unmasked assessment. The registry record does not report a primary endpoint confidence interval or a statistical method for calculating one.

For binary outcomes, precision depends in part on the amount of information in the analyzed groups and on the event frequency. The registry record does not provide the primary event counts or denominators, so precision cannot be reconstructed. No new estimate should be inferred from the overall enrollment figure or from adverse-event counts, because those numbers refer to different populations or outcomes.

What does non-random allocation change?

In general, random allocation is intended to make treatment groups comparable with respect to baseline characteristics, on average. Non-random allocation does not provide that protection. If the dose groups differ in clinical status or other characteristics that also influence rescue medication, a group contrast can reflect those differences as well as dose. The registry record does not describe how dose assignment occurred, whether baseline variables were compared, or whether adjusted analyses were planned or conducted.

Masking is recorded as none. In general, knowledge of treatment can influence care decisions and outcome assessment, particularly when an endpoint depends on a decision to administer medication. This does not establish that decisions were biased in this study; it identifies a potential source of interpretive uncertainty. The record does not report blinded outcome adjudication or standardized rescue thresholds.

How should the planning illustrations be understood?

In general, a sample-size calculation is a planning exercise about how much information a future study might need under specified assumptions. It is not a measure of the probability that a completed study found a real effect. The stated planning approach uses a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a fraction of the observed effect. Such an illustration is conditional on its assumptions and is not the trial’s own sample-size justification. It should not be described as observed power. The registry record does not report a sample-size justification, the numeric planning results, or the primary observed effect needed to assess the illustration.

The planning description distinguishes participant-per-arm calculations from total-event calculations for time-to-event outcomes. That distinction reflects the different information structures of binary or other non-time-to-event outcomes and time-to-event analyses. It does not establish that a time-to-event model was used for the primary outcome. The primary endpoint is a binary rescue-medication measure; time to successful extubation is listed separately as a secondary outcome. The record does not report an analysis of that secondary outcome.

Are there reported inferential analyses?

The registry record reports no analyses. It does not identify a test, model, covariate adjustment strategy, confidence interval method, or prespecified contrast for the primary outcome. Therefore, no p-value or adjusted effect estimate can be interpreted from the record. General statistical guidance can explain what such methods would mean if reported, but cannot supply missing results or establish which methods were actually used.

Overall, the available methodological description identifies the endpoint, study design, dose arms, and planning assumptions, but does not provide the outcome data or inferential methods needed to estimate a dose-group difference. The primary result and its uncertainty are not reported in the registry record.

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("Dexmedetomidine 0.05 mcg/kg", "Dexmedetomidine 0.1 mcg/kg", "Dexmedetomidine 0.2 mcg/kg")
n      <- c(14, 14, 8)
events <- c(1, 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  Dexmedetomidine 0.05 mcg/kg  14  1  7.1  0.2  33.9  1.3  31.5  1.7  31.9
ARM  Dexmedetomidine 0.1 mcg/kg  14  1  7.1  0.2  33.9  1.3  31.5  1.7  31.9
ARM  Dexmedetomidine 0.2 mcg/kg  8  2  25.0  3.2  65.1  7.1  59.1  7.5  60.0

11. Multiplicity, Missing Data and Analysis Populations

The primary outcome is rescue midazolam use for sedation. The registry record also lists secondary outcomes covering rescue medication for analgesia, total and weight-adjusted rescue medication amounts, and time to successful extubation. Looking at multiple outcomes can increase the chance of finding an apparently notable result by chance if each is tested separately. In general, multiplicity procedures may control that risk or distinguish a primary confirmatory outcome from exploratory outcomes. A multiplicity strategy is not reported in the registry record.

The record reports no analyses, so it does not provide a hierarchy of tested outcomes, p-values, or adjusted inferences. It is not possible to determine whether secondary outcomes were analyzed as confirmatory or exploratory, or whether any adjustment was used. A list of planned or registered outcomes alone does not establish which analyses were conducted or how their results should be interpreted.

Missing-data rules are also not reported in the registry record. The primary population is described as subjects who received dexmedetomidine for at least 6 hours, but the record does not state how missing rescue-medication information, early discontinuation, or incomplete observation was handled. It does not report whether subjects were excluded for missing outcomes, whether any imputation was performed, or how missingness was assessed. These omissions matter because the available observation period and analysis population can affect a percentage.

The analysis-population description contains a wording conflict: it refers to “randomized Dexmedetomidine,” while allocation is recorded as non-randomized. The registry record does not clarify this inconsistency. It also does not report the analyzed population size for the primary endpoint. Readers should not assume that enrollment, the efficacy-evaluable population, and the denominator for each secondary outcome are the same.

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 2.8% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: bradycardia (7.1%), cardio-respiratory arrest (7.1%), oxygen saturation decreased (7.1%).

The serious adverse-event summaries give at-risk and affected counts by dexmedetomidine dose group. For 0.05 mcg/kg, 0 serious adverse events are listed among 14 at risk; for 0.1 mcg/kg, 1 is listed among 14 at risk; and for 0.2 mcg/kg, 0 are listed among 8 at risk. Death counts are not reported in the registry record. These are descriptive counts, not evidence by themselves that a dose caused or prevented an event.

The separately tabulated other-adverse-event counts are 7 among 14 at risk for 0.05 mcg/kg, 9 among 14 at risk for 0.1 mcg/kg, and 6 among 8 at risk for 0.2 mcg/kg. No comparative statistical analysis is reported. The record also lists bradycardia, cardio-respiratory arrest, and decreased oxygen saturation among serious-event terms, each at 7.1%. It does not identify the dose group for each listed term in the summary.

In general, an at-risk count gives context for the number affected, but these small group summaries are descriptive and may be imprecise. They do not establish that event frequencies differ between doses. The registry record does not provide event-level timing, duration, severity details beyond the serious-event classification, or causal attribution. Safety counts should be read separately from the unreported primary efficacy result.

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

The registry record establishes that a completed study examined dexmedetomidine safety, efficacy, and pharmacokinetics at three dose levels in neonates from 28 to 44 weeks gestational age. It identifies rescue midazolam use for sedation during infusion as the primary endpoint and describes the eligible efficacy population. It also gives selected serious and other adverse-event counts by dose group. These elements describe the study’s question and some safety reporting, but they do not provide the numerical primary outcome result.

Accordingly, the posted registry information does not show what percentage of the efficacy-evaluable population received rescue midazolam, how that percentage varied by dose, or how precisely any difference was estimated. It cannot support a statement that one dose led to more or less rescue use than another. Nor does the absence of primary results mean that no events occurred; it means the primary numerical results are not reported in the registry record.

In general, an observed difference between groups is not automatically a causal treatment effect. This distinction is especially important in a non-randomized study, where group assignment may be related to characteristics that also influence outcomes. Lack of masking can also matter when the endpoint depends on a clinical decision. The registry record does not report adjustment methods or procedures that would resolve these concerns.

The serious-event summaries provide counts, but do not establish comparative safety or causation. The record does not report death counts, and the listed serious-event terms are not mapped to specific dose groups in the summary. Without complete outcome detail, uncertainty estimates, and analytic methods, safety and efficacy conclusions should remain limited to the descriptive information actually reported.

In short, the record documents a dose-level study and names its primary endpoint, but does not report the primary endpoint findings. The trial’s stated objectives and design should not be mistaken for evidence of a particular outcome. The numerical rescue-medication result, its denominator, and its uncertainty are not reported in the registry record.

14. Why This Trial Matters Statistically

This study raises several statistical issues that commonly arise in early clinical research: dose-group comparisons, binary outcomes based on care decisions, and interpretation when allocation is not randomized. The primary endpoint is straightforward to state—whether rescue midazolam was received during infusion—but its meaning depends on consistent criteria for giving rescue medication and a clearly defined analysis population. The registry record identifies the outcome and population definition, while leaving the operational criteria and numerical results unreported.

Non-randomized allocation makes the comparison a useful example of the distinction between association and causation. In general, comparing groups can reveal patterns, but differences in baseline characteristics or clinical care may influence observed outcomes. Statistical adjustment can sometimes address measured differences, but it cannot guarantee removal of unmeasured confounding. The registry record does not report whether adjustment was performed.

The record also illustrates why results need more than an endpoint label. A percentage requires a numerator and denominator, and interpretation benefits from an uncertainty interval and a clear description of analysis methods. Without those elements for the primary outcome, readers cannot assess the magnitude or precision of a dose-group pattern. The adverse-event counts are informative as descriptive summaries, but they are not substitutes for an unreported efficacy endpoint or for a formal comparative safety analysis.

Finally, the wording conflict between non-randomized allocation and a population description referring to randomized dexmedetomidine highlights the importance of consistent registry documentation. Clarifying that terminology would help readers understand which participants were included and how assignment occurred. The statistical value of the record is therefore partly methodological: it shows what was intended to be measured while also making clear where reporting gaps constrain interpretation.

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 outcome’s numerical results are not reported in the registry record. No event count, denominator, percentage, confidence interval, or group-specific estimate is available. This prevents assessment of the observed rescue-midazolam frequency, the size of any dose-group contrast, or its precision. The registry record also reports no analyses, leaving the statistical test or model, planned contrasts, and adjustment methods unspecified.

The study is marked non-randomized and unmasked. Those design features constrain causal interpretation because groups may differ in relevant characteristics and treatment knowledge may influence decisions about rescue medication. The registry record does not explain the assignment process, provide baseline comparisons, or describe methods to address possible confounding. It also does not state rescue-medication criteria, making it difficult to assess how consistently the endpoint was applied.

The efficacy-evaluable population is described as participants who received dexmedetomidine for at least 6 hours, but the analyzed number and missing-data handling are not reported. The description’s reference to “randomized Dexmedetomidine” conflicts with the non-randomized allocation designation. The registry record does not resolve the discrepancy or clarify whether the population wording reflects the actual analysis.

Safety reporting is also limited in the registry summary. Death counts are not reported, and the listed serious-event terms are not assigned to dose groups there. The adverse-event counts are descriptive, with no comparative analysis or uncertainty estimates reported. The record does not report detailed event timing or causal attribution. These limitations do not imply that unreported information was absent from study files; they mean it is not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety, Efficacy and Pharmacokinetic Study of Dexmedetomidine in Pediatrics Ages ≥28 Weeks to ≤44 Weeks Gestational Age — NCT01159262.
• Registry record last updated 2015-08-13; status last verified 2015-07.
• Results first posted 2014-12-12.
• 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

NCT01159262 is a completed Phase II/III, open-label, multicenter, non-randomized parallel study of dexmedetomidine in neonates from 28 to 44 weeks gestational age. Enrollment is listed as 36. The three dose arms used loading and maintenance doses of 0.05 mcg/kg and 0.05 mcg/kg/hr, 0.1 mcg/kg and 0.1 mcg/kg/hr, or 0.2 mcg/kg and 0.2 mcg/kg/hr.

The primary endpoint was the percentage receiving rescue midazolam for sedation during dexmedetomidine infusion, among the stated efficacy-evaluable population. Numerical primary outcome results and analyses are not reported in the registry record. Serious and other adverse-event counts are listed by dose group, but remain descriptive; death counts are not reported. The allocation designation and efficacy-population wording conflict regarding randomization, and the registry record does not resolve that inconsistency.