Premedication With Melatonin and Alprazolam Combination Versus Alprazolam or Melatonin Alone: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Premedication With Melatonin and Alprazolam Combination Versus Alprazolam or Melatonin Alone (NCT01486615), a randomized phase 4 study. The primary outcome is Change in VAS Anxiety Score Relative to Baseline After Premedication.

2. Clinical Question

The clinical question is therefore about short-term change in a patient-reported anxiety measure, not about anxiety over a longer follow-up period. The registered study also asked questions about sedation, orientation, memory, and propofol consumption. Those outcomes can add context about the preoperative period, but they do not replace the stated primary endpoint. The record does not report a primary comparison of the combination directly against either single-drug group; the posted primary comparisons use placebo as the reference.

3. Trial Design

The registry describes a completed, phase 4, randomized, parallel-group study with triple masking and placebo control. It enrolled 80 patients and lists anxiety as the condition. The sponsor was B.P. Koirala Institute of Health Sciences. The recorded study start was 2011-10, and primary completion was 2012-01.

Participants were assigned to melatonin, the melatonin–alprazolam combination, alprazolam, or a similar-looking placebo. The registry describes oral premedication approximately 1–2 hours before anesthesia; the brief summary describes administration approximately 90 minutes before surgery. These descriptions place the intervention in the preoperative period, but the record does not report further details of the randomization procedure, allocation concealment, or how masking was maintained.

The primary outcome was mean change from baseline in VAS anxiety score at 15 minutes after premedication. The posted group summaries include 20 participants per group for this endpoint. For several secondary outcomes, the posted group counts are lower in some arms, and the counts differ by outcome. The registry record does not explain these changes in available counts or give a participant flow account.

Although the study is marked completed, the record lists no reported analyses. The posted results therefore include group summaries and unadjusted comparisons, but the registry record does not report a full statistical analysis plan or an account of how the study investigators analyzed the outcomes. The record also does not report whether any interim analyses occurred or how the sample size for the original trial was justified beyond the description attached to the primary outcome.

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.

Before assignment: One hundred and ten patients were assessed for eligibility, 98 patients had anxiety VAS ≥3. Among them, 80 patients who met the inclusion criteria, were enrolled and assigned into four groups.

Overall Study

Analysis population for the primary outcome, as defined in the registry: sample size of 16 patients in each group was determined by a power analysis (α, 0.05; β, 0.10) assuming that there will be 50% reduction in anxiety VAS from baseline in the experimental groups and 4% in the placebo group. To compensate for dropout cases and shifting from normality in data distribution, 20 cases were studied in each group.

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 Change in VAS Anxiety Score Relative to Baseline After Premedication, measured over Change from baseline in VAS anxiety score at 15 minutes after premedication.

The primary endpoint is change from baseline in VAS anxiety score at 15 minutes after premedication. The scale is described as a 10 cm visual analogue scale, with a patient-facing color gradient from white to black and a clinician-facing score from 0 to 10. A score of 0 corresponds to no anxiety, while 10 corresponds to anxiety as bad as it can be. The patient indicates the point that reflects their anxiety, and the clinician records the corresponding score.

Change from baseline is used to describe whether anxiety scores moved after premedication, rather than relying only on a single post-treatment score. The registry explains that a greater reduction from baseline represents a better outcome. The posted primary summaries are means with standard deviations, so they describe the average change within each group and the spread of individual changes around that average. They do not show each participant’s response or the distribution of scores.

This endpoint captures a short-term, self-reported measure at a specified time after premedication. It does not, by itself, describe anxiety at other times, sleep quality, recovery, or longer-term outcomes. The record does not report a clinically important difference threshold for the scale, so the clinical importance of a particular numerical change cannot be determined from the registry information alone.

7. Results Posted in the Registry

• Melatonin: mean 0.35 versus 0.25 on control; difference 0.10 (95% CI -0.40 to 0.60), standardized effect d = 0.12; z-test p = 0.693.
• Melatonin and Alprazolam: mean 0.70 versus 0.25 on control; difference 0.45 (95% CI -0.33 to 1.23), standardized effect d = 0.36; z-test p = 0.261.
• Alprazolam: mean 0.65 versus 0.25 on control; difference 0.40 (95% CI -0.23 to 1.03), standardized effect d = 0.39; z-test p = 0.215.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Number of Patients With Intact Memory

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Melatonin: 65.0% (13/20) versus 77.8% (14/18) on control; risk difference -12.8 percentage points (95% CI -41.2 to 15.6), risk ratio 0.84 (0.56–1.25); unadjusted two-proportion z-test p = 0.386.
  • Melatonin and Alprazolam: 21.1% (4/19) versus 77.8% (14/18) on control; risk difference -56.7 percentage points (95% CI -83.3 to -30.2), risk ratio 0.27 (0.11–0.67); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Melatonin and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Melatonin and Alprazolam than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Amount of Propofol Consumption

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Melatonin: mean 79.20 versus 75.80 on control; difference 3.40 (95% CI -8.28 to 15.08), standardized effect d = 0.20; z-test p = 0.568.
  • Melatonin and Alprazolam: mean 65.50 versus 75.80 on control; difference -10.30 (95% CI -25.22 to 4.62), standardized effect d = -0.45; z-test p = 0.176.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Melatonin and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Melatonin and Alprazolam and the control. The interval gives the range of effects that remain compatible with the data.

Number of Patients With Loss of Memory for Being Transferred to Operating Room.

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Melatonin: 5.0% (1/20) versus 0.0% (0/18) on control; risk difference 5.0 percentage points (95% CI -4.6 to 14.6); unadjusted two-proportion z-test p = 0.336.
  • Melatonin and Alprazolam: 26.3% (5/19) versus 0.0% (0/18) on control; risk difference 26.3 percentage points (95% CI 6.5 to 46.1); unadjusted two-proportion z-test p = 0.019.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Melatonin and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Melatonin and Alprazolam than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes provide a broader but less definitive picture than the primary anxiety endpoint. They cover memory at 24 hour after surgery, loss of memory for transfer to the operating room, and propofol consumption, while the registry’s outcome list also names sedation and orientation measures. The outcome counts and available comparisons vary. The record does not provide reported analyses for all listed secondary outcomes, so the full outcome pattern cannot be reconstructed from the registry information.

Across the posted secondary comparisons, some estimates are more distinct from zero than the primary anxiety estimates, while others remain compatible with no difference. This mixed pattern does not amount to a single consistent finding across all outcomes. Memory, propofol use, and short-term anxiety measure different aspects of the perioperative experience, so an apparent pattern in one outcome does not automatically confirm a pattern in another.

Secondary results generally carry less weight when many outcomes or comparisons are examined without a reported plan for handling multiplicity. The more opportunities there are to observe a low unadjusted p-value, the greater the risk that a nominally notable result arose by chance. The registry record does not say which outcomes were designated as secondary before analysis, whether all planned secondary outcomes were reported, or whether any multiplicity adjustment was used.

These results are best viewed as exploratory context for the primary finding, not as an independent confirmation of it. The record does not report a hierarchy of testing, a prespecified set of key secondary outcomes, or an analysis plan that would establish how secondary results were intended to support the primary question. Differences in available participant counts across outcomes add further uncertainty.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Sedation Score at One Hour After Premedication
• Orientation Score
• Number of Patients With Intact Memory
• Amount of Propofol Consumption
• Number of Patients With Loss of Memory for Being Transferred to Operating Room.

9. Statistical Interpretation

10. Statistical Methods Explained

What does a mean difference describe?

The primary outcome is continuous: each participant has a VAS anxiety score change, and the registry reports a mean and standard deviation for each group. A mean difference compares the average change in an active-treatment group with the average change in the placebo group. A positive mean difference in the posted comparisons means that the active group’s reported mean change is numerically higher than placebo’s, given the comparison’s stated direction. That arithmetic description does not alone establish a meaningful or reliable treatment effect.

The standard deviation describes how dispersed individual observations are around a group mean. It is not the uncertainty of the mean itself and does not indicate the range containing every participant’s result. People may vary considerably even when a group mean appears fairly precise, and a mean may conceal differences in the shape of the outcome distribution.

What do confidence intervals add?

A confidence interval gives a range of values compatible with the observed data under the method used to calculate it. For these comparisons, the interval helps show how precisely the mean difference is estimated. When an interval includes zero, the data are compatible with no average difference as well as with differences in either direction represented by the interval. An interval that excludes zero indicates a statistically distinguishable difference under the calculation used, but it does not by itself establish clinical importance or remove concerns about bias and multiple testing.

The posted primary comparisons are unadjusted calculations from the group summary statistics. The registry record lists no reported analyses, so it does not provide an investigator-reported model or adjusted primary estimate to compare with these calculations. The record does not report adjustments for baseline covariates, stratification factors, or any other variables.

How should p-values be read?

A p-value measures how surprising data at least as incompatible with a specified null hypothesis would be if that null hypothesis and the assumptions of the test were true. It is not the probability that the null hypothesis is true, nor the probability that chance alone caused the observed result. The primary p-values are unadjusted, so they do not account for the several treatment comparisons or the other outcomes listed in the registry.

A p-value should be interpreted alongside the effect estimate and confidence interval. A result with a comparatively small p-value can still have uncertainty about its size, and a larger p-value does not demonstrate that groups are equivalent. Equivalence or non-inferiority would require a defined margin and an analysis suited to that question; such details are not reported in the registry record.

What are the binary-outcome measures?

Memory outcomes are reported as participant counts, and the comparison calculations include risk differences. A risk difference expresses the difference between the observed proportions in two groups. Its confidence interval communicates uncertainty in that difference. The interval’s direction depends on which group’s proportion is subtracted from which; the posted comparisons use placebo as the reference. The record also contains relative risk and odds ratio summaries for one memory comparison, but does not report an investigator analysis using these measures.

For binary outcomes, the number of events and the number of participants with outcome data both matter. Small counts can make estimates imprecise, and a zero count in one group can complicate relative measures. The registry’s posted summary calculations should therefore be read with attention to the underlying group counts and interval width, rather than treating a point estimate as exact.

What can and cannot be inferred from the posted calculations?

The comparison statistics are unadjusted and based on the posted group summaries. They are not evidence that a prespecified analysis was conducted in the same way by the study investigators. The registry record does not report the statistical test, model, missing-data method, analysis population, or any adjustment for multiple comparisons. It also does not report diagnostic checks or distributional information for the continuous outcomes. These omissions limit the ability to assess whether the calculations match the investigators’ intended analysis.

In general, randomization is intended to make treatment groups comparable on average, while masking can reduce some risks of biased treatment delivery or outcome assessment. Those design features do not guarantee that all sources of bias are absent. The registry does not report enough procedural detail to assess the randomization implementation, concealment, masking success, or possible departures from assigned treatment. Statistical results must be considered alongside these design and reporting uncertainties.

11. Confidence Intervals and Precision

The primary mean-difference estimates are 0.1 cm for melatonin versus placebo, 0.45 cm for the combination versus placebo, and 0.4 cm for alprazolam versus placebo. Their respective confidence intervals are -0.396 to 0.596, -0.334 to 1.234, and -0.232 to 1.032. Each interval includes zero, so each comparison remains compatible with no average difference as well as with differences on either side of zero. The interval for the combination is wider than the interval for melatonin, reflecting less precision in that comparison’s posted estimate.

Confidence-interval width is important because the same point estimate can be compatible with substantially different underlying effects depending on the amount of information and variability. Here, the primary confidence intervals are broad relative to the point estimates. That means the study’s estimates do not sharply distinguish among possible magnitudes of the mean difference. The p-values likewise do not provide a measure of the likely size or practical importance of an effect.

The posted group standard deviations also vary: 0.8 cm for melatonin, 1.6 cm for the combination, 1.2 cm for alprazolam, and 0.8 cm for placebo. A standard deviation describes spread among observations, whereas a confidence interval describes uncertainty about a comparison estimate. Neither identifies the individual response pattern or whether changes are clinically meaningful.

Precision is also affected by which participants have outcome data. The primary summaries list 20 participants in each group, while some secondary summaries have lower counts. The registry record does not explain missing observations or report whether their absence could have influenced estimates. Consequently, even a confidence interval calculated from the posted summaries cannot address uncertainty introduced by unreported missing-data processes or analysis choices.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, rather than total participants across arms or total events. The comparisons in this study are not time-to-event outcomes, so the event-total convention does not apply. The planning illustration assumes a two-sided significance level of 0.05, equal allocation between the two arms being compared, and a normal approximation. It considers effects equal to the stated fraction of the observed effect: 100%, 75%, or 50%.

The 80% power column gives the planned number of participants per arm under those assumptions for a design intended to have an 80% probability of detecting the stated effect if that effect is real and the assumptions hold. The 90% column gives the corresponding per-arm planning figure for a higher target probability of detecting it. These are design calculations, not observed results from the trial. Smaller target effects require more participants because they are harder to distinguish from random variation.

These illustrations are based on the observed effect estimates, so they should not be treated as a definitive design recommendation. Observed effects can be unstable, especially when estimated from small groups, and the calculation uses simplified assumptions. The registry’s description of the original primary-outcome planning states 16 patients in each group and refers to alpha, beta, and assumed reductions in anxiety, but it does not provide a complete account of the original design rationale. The planning illustration and the trial’s own original design assumptions are separate matters. This is not observed power.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.100; pooled standard deviation σ = 0.800.
2. n = 2 × (1.96 + 0.842)² × 0.800² / 0.100² = 1,004.7, rounded up to 1,005 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.1                      # observed difference in means
sigma <- 0.8                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1486615)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 1,005 (80% power), 1,345 (90% power)
 75% of observed effect: n per arm = 1,787 (80% power), 2,392 (90% power)
 50% of observed effect: n per arm = 4,019 (80% power), 5,380 (90% power)
power.t.test: 1005.6 
Simulated power at n = 1,005 per arm: 0.797 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The study has several treatment groups and multiple outcomes, creating a multiplicity issue: repeated testing can increase the chance of at least one apparently notable result even when there is no underlying effect. The posted p-values are unadjusted. The registry record does not report a prespecified testing hierarchy, a family of comparisons, or a multiplicity adjustment, so secondary p-values should not be interpreted as though they were protected against this issue. The record does not clarify whether the primary comparisons were part of a defined testing sequence.

Missing-data reporting is limited. The primary summaries list 20 participants per group, while secondary summaries list fewer participants in some groups. The registry record does not explain why the available counts differ, whether outcomes were missing, whether participants withdrew, or how missing observations were handled. It also does not report whether the analyses followed an intention-to-treat, per-protocol, or other population definition.

Without a participant flow account and outcome-specific missingness information, it is difficult to assess whether the observed summaries represent all randomized participants or whether the available cases could differ systematically from those without data. No imputation method, sensitivity analysis, or missing-at-random assumption is reported in the registry record. The effect of missingness on the estimates therefore cannot be evaluated from these results.

The registry record lists no reported analyses and does not specify the statistical model or test used by the investigators. It does not report whether baseline adjustment, covariate adjustment, or other model features were used. Nor does it report an interim-analysis plan, stopping rules, or prespecified subgroup analyses. These are unreported details, not evidence that such procedures did or did not occur. They limit independent assessment of how the study’s results were generated and selected for reporting.

15. 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 zero serious adverse events among the participants listed at risk in each group: 20 for melatonin, 19 for the combination, 18 for alprazolam, and 18 for placebo. This means no serious adverse event was recorded in those group summaries. The counts do not establish that the risk of a serious event is absent; uncommon events may not appear in a study of this size, and the registry record does not provide event descriptions or a detailed safety analysis.

Death counts are not reported in the registry record. The record also lists other adverse events affecting 13 participants in the melatonin group, 12 in the combination group, 14 in the alprazolam group, and 16 in the placebo group. Those figures do not identify the events, their severity, timing, or relationship to study treatment. They should not be treated as evidence of causation or as a complete account of safety.

Safety comparisons require context about how events were defined, collected, and assessed. Those details are not reported in the registry record. The available figures are descriptive counts rather than a comprehensive comparison of safety risks.

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

The primary outcome is a short-term measure of change in reported anxiety after premedication. The posted estimates show modest differences in group means relative to placebo, but their confidence intervals include zero and the unadjusted p-values do not provide clear statistical evidence of a difference. This means the registry results leave substantial uncertainty about the direction and size of any primary-outcome differences.

That uncertainty should not be translated into a claim that the groups are identical. A study may fail to distinguish a difference from zero even when the true difference is not zero, particularly when estimates are imprecise. Conversely, a numerical difference in group means is not enough to establish that treatment caused a meaningful change. The record does not report a threshold for clinical importance on the VAS, and it does not provide an analysis that directly compares the combination with either single treatment.

Secondary outcomes add observations about memory and propofol consumption, but their unadjusted nature and the number of outcomes make isolated results less conclusive. The registry’s limited reporting of analysis methods, outcome availability, and missing-data handling further restricts what can be inferred. The findings describe the posted summaries for this trial; they do not establish how the treatments would perform in other populations or settings.

The serious adverse event summaries contain no recorded serious events in the listed at-risk groups, while death counts are not reported. These data are too limited to establish the absence of risk. The registry information is best understood as a record of observed group summaries with uncertainty, not as a definitive assessment of efficacy, equivalence, or safety.

17. Why This Trial Matters Statistically

This trial illustrates why interpretation should begin with the endpoint and comparison rather than with a single p-value. The primary question concerns change from baseline on a patient-reported anxiety scale at a specific time. The group means, mean differences, standard deviations, confidence intervals, and p-values each describe a different part of the evidence: average change, contrast between groups, variability, precision, and compatibility with a null hypothesis under stated assumptions.

It also demonstrates the distinction between a randomized design and complete reporting. Randomization and masking are important design features, but the registry record does not provide enough detail to assess implementation or the analysis population. Secondary outcomes may offer useful context, yet multiple unadjusted comparisons make isolated findings less secure. Counts that differ across outcomes also show why participant availability and missing-data handling matter.

Finally, the posted planning illustrations emphasize that sample-size calculations depend on the effect a future study is designed to detect. A design aimed at detecting a smaller effect requires more participants under the stated assumptions. Those planning figures are not evidence about the power actually achieved in this completed study. The key statistical lesson is to treat estimates as uncertain, distinguish descriptive summaries from reported investigator analyses, and avoid turning a non-significant result into a claim of no effect.

18. 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.

Several limitations are specific to the available record. The primary endpoint is a self-reported anxiety measure, and the registry does not report whether the scale was administered consistently or whether assessors and participants remained successfully masked. The outcome is recorded at a short time after premedication, so it does not describe anxiety at other stages or longer-term outcomes.

The registry’s brief summary describes eligibility and intended treatment timing, but the record does not provide detailed participant flow, reasons for any outcome-specific differences in available counts, or information about adherence to assigned premedication. It does not explain the randomization sequence, allocation concealment, or masking procedures. These omissions limit assessment of possible selection, performance, or assessment biases.

The statistical reporting is also incomplete. No investigator analyses are listed, and the registry record does not report the analysis method, analysis population, missing-data approach, or multiplicity strategy. The posted unadjusted comparisons therefore cannot be checked against a stated prespecified analysis plan. The record does not report a clinically important difference for the anxiety scale, which limits interpretation of the magnitude of the estimated changes.

Several secondary outcomes are listed, but not all have posted comparison calculations. Some available secondary counts are smaller than the primary endpoint counts, with no explanation in the registry record. These factors, along with the broad primary confidence intervals, mean that the findings are uncertain and that the posted results alone do not support strong conclusions.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Premedication With Melatonin and Alprazolam Combination Versus Alprazolam or Melatonin Alone — NCT01486615.
• Registry record last updated 2012-10-05; status last verified 2012-09.
• Results first posted 2012-10-05.
• 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.

22. Record Summary

The registry describes a completed, randomized, parallel-group, triple-masked, placebo-controlled phase 4 study of preoperative melatonin, alprazolam, their combination, and placebo in patients with anxiety scheduled for general anesthesia. Registered enrollment was 80. The primary endpoint was mean change from baseline in VAS anxiety score at 15 minutes after premedication.

Primary mean differences versus placebo had confidence intervals that included zero. Secondary results were mixed, and the posted comparisons are unadjusted. Serious adverse event counts were zero in the listed groups; death counts are not reported in the registry record. The registry does not report investigator analyses, a complete analysis plan, or explanations for outcome-specific differences in available counts. The results are therefore best read as uncertain summaries rather than definitive treatment comparisons.