Efficacy of Aerobic Exercise Added to Alprazolam in Panic Disorder Treatment: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy of Aerobic Exercise Added to Alprazolam in Panic Disorder Treatment (NCT00803400), a randomized phase 4 study. The primary outcome is Participants´Endpoint Change From Baseline in Hamilton Anxiety Rating Scale.

2. Clinical Question

The primary outcome is a continuous measure of anxiety symptom severity, reported as a mean with a standard deviation. The posted arm means are 22.59 for alprazolam and 22.73 for alprazolam plus aerobic exercise. The unadjusted re-calculation gives a mean difference of 0.14, with the exercise-combination arm higher. Its confidence interval includes values on both sides of no difference, and the unadjusted p-value is 0.674. These summary statistics do not, by themselves, establish that the plans differ.

The registry also reports a one-sided t-test with a result value of 1 and p < 0.001. That reported result conflicts with the re-calculation from the posted arm summaries. The record does not explain the discrepancy or give enough detail to reconcile the analyses. The sponsor’s own analysis takes precedence, while the re-calculation should be read as a separate, unadjusted check rather than a replacement for the trial analysis.

3. Trial Design

The registry identifies this as a randomized, parallel-group phase 4 trial, with no masking. It lists an enrollment of 150 and a completed status. The study is sponsored by the University of Buenos Aires. The recorded start date is 2008-10-01, and the primary completion date is 2009-03-01. The registry record does not report the study setting or the method used to generate or conceal the allocation sequence.

The two groups were assigned to alprazolam alone or alprazolam plus aerobic exercise. The posted primary outcome summaries list 75 participants in each arm. Those summaries report a mean and standard deviation for the Hamilton Anxiety Rating Scale outcome at 12 weeks. The primary endpoint is described as endpoint change from baseline, but the registry record does not explain the precise calculation of change, how baseline measurements were handled, or whether the displayed values are change scores or another endpoint representation.

“Randomized” means assignment to the study groups was intended to occur by chance, which can reduce systematic differences between groups at the start of a trial. A parallel-group design means participants were assigned to one plan rather than being described as receiving both plans in sequence. The record does not report the allocation ratio as a protocol feature, although the posted primary outcome summaries have equal arm sizes.

No masking was reported. This means the registry does not indicate that participants, clinicians, or outcome assessors were masked to assigned treatment. The record does not identify which people, if any, knew assignment during data collection or analysis. It also does not report details of follow-up, adherence, withdrawals, or the population included in the primary analysis. The trial’s original sample-size justification and statistical plan are not reported in the registry record.

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: 30 selected patients were not included: 12 did not match the 20 points for the Hamilton Anxiety Scale; 10 had history of medical diseases (5 of hypothyroidism, 4 of hypertension, and 1 of chronic fatigue syndrome); 8 had other associated psychiatric diseases: (5 had major depressive disorder and 3 had social anxiety disorder).

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Participants´Endpoint Change From Baseline in Hamilton Anxiety Rating Scale, measured over 12 weeks.

The primary endpoint is Participants’ Endpoint Change From Baseline in the Hamilton Anxiety Rating Scale at 12 weeks. The scale has 14 items, each rated on a 5-point ordinal scale from 0, “not present,” to 4, “severe.” Its total score ranges from 0 to 56. The registry description says the items cover psychic anxiety, including mental agitation and psychological distress, and somatic anxiety, including physical complaints related to anxiety. It also gives score ranges for mild, mild to moderate, and moderate to severe symptom severity.

A clinician-rated scale that combines mental and physical symptoms can provide a structured way to quantify anxiety severity. Expressing the result as a mean allows a group-level comparison of the continuous scores, while the standard deviation describes how dispersed the scores are within each arm. The endpoint is described as change from baseline, so its intended role is to capture how scores shifted over the trial rather than only the score at one time point.

There is an important reporting limitation: the registry record does not specify the arithmetic convention for change, such as whether a reduction is represented by a negative or positive value, or how baseline values contributed to the analysis. The posted endpoint values therefore need to be interpreted according to the registry’s wording and should not be assigned a direction of clinical improvement without that detail.

7. Results Posted in the Registry

• Alprazolam + Aerobic Exercise: mean 22.73 versus 22.59 on control; difference 0.14 (95% CI -0.51 to 0.79), standardized effect d = 0.07; z-test p = 0.674.

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.

Participants´Endpoint Change From Baseline in Clinical Global Impression Severity Scale (CGI-S)

• 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:
  • Alprazolam + Aerobic Exercise: mean 4.06 versus 4.05 on control; difference 0.01 (95% CI -0.07 to 0.09), standardized effect d = 0.04; z-test p = 0.794.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Alprazolam + Aerobic Exercise and the control. The interval gives the range of effects that remain compatible with the data.

Participants´Endpoint Change From Baseline in Clinical Global Impression Improvement Scale (CGI-I)

• 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:
  • Alprazolam + Aerobic Exercise: mean 1.86 versus 2.70 on control; difference -0.84 (95% CI -1.07 to -0.61), standardized effect d = -1.38; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Alprazolam + Aerobic Exercise than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry lists two secondary outcomes, both based on Clinical Global Impression scales. Across these outcomes, the pattern is not uniform: the posted severity-scale comparison is close to no difference, while the improvement-scale comparison is more separated and its unadjusted interval excludes zero. These outcomes differ from the primary Hamilton Anxiety Rating Scale endpoint, so they offer additional but not interchangeable views of symptoms and clinical status.

The secondary pattern does not settle the primary result. A secondary measure may capture a related aspect of the clinical picture, but it does not automatically confirm or overturn a primary endpoint. The primary comparison itself has a discrepancy between the sponsor’s reported analysis and the unadjusted recalculation. The secondary comparisons are recalculated from their posted summaries and should be interpreted separately from that sponsor analysis.

Unadjusted secondary results carry less weight when several outcomes are examined. Each additional test creates another opportunity for a result to appear unusually strong by chance, particularly if no adjustment or prespecified hierarchy is used. The registry record does not report a multiplicity correction, a hierarchy for testing outcomes, or whether the secondary analyses were prespecified in the statistical plan. This means the displayed unadjusted p-values should be considered exploratory rather than treated as independently confirmatory evidence.

The record also does not provide full details on the scoring direction or analysis population for these measures. Differences in the participants contributing to an outcome can affect how results compare across measures. Accordingly, the overall secondary pattern is useful context, but it should not be collapsed into a single claim about the treatment plans or used to resolve the primary analysis conflict.

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

• Participants´Endpoint Change From Baseline in Clinical Global Impression Severity Scale (CGI-S)
• Participants´Endpoint Change From Baseline in Clinical Global Impression Improvement Scale (CGI-I)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: each participant’s result is represented by a score on the Hamilton Anxiety Rating Scale, and the registry summarizes each arm using a mean and standard deviation. A mean describes the central value of the group scores. A standard deviation describes their spread around that mean. Neither quantity reveals the full distribution of individual scores, so the summaries cannot show whether scores were skewed, clustered, or affected by unusual observations.

What does the unadjusted mean difference represent?

The recalculation subtracts the alprazolam-alone mean from the alprazolam-plus-exercise mean. The resulting estimate is 0.14. This is an unadjusted difference between the posted group summaries: it does not account for baseline values or other participant characteristics. A positive value means the posted numerical mean is higher in the exercise-combination arm. Whether that direction corresponds to more or less improvement depends on the change-score convention, which the registry record does not explain.

The calculation also uses the posted arm sizes and standard deviations. It is useful as a transparent check on the reported summaries, but it does not reproduce the sponsor’s one-sided t-test. In particular, the registry’s reported parameter is labeled as a difference in final values, while the primary outcome title describes change from baseline. The record does not establish that these are identical analysis quantities.

Why does variability matter?

The standard deviations describe variation among participants within each arm. The uncertainty of a difference between means depends both on the spread of scores and on how many observations contribute. Wider dispersion generally makes a group contrast less precise; more observations generally make it more precise, all else being equal. These are general statistical principles, not additional findings about the trial. The posted primary standard deviations are 2.09 and 1.98.

A t-test evaluates a mean contrast relative to its estimated uncertainty under the test’s assumptions. The registry identifies the sponsor’s test as one-sided, meaning that its formal test evaluates a difference in a prespecified direction rather than departures in either direction. The record does not report the directional hypothesis, the rationale for using a one-sided test, or the other details of the test. A one-sided result should not be treated as interchangeable with a two-sided test.

What does the confidence interval add?

A confidence interval gives a range of values compatible with the estimate under the method used to construct it. It communicates uncertainty in the size and direction of the contrast, rather than only whether a test crosses a chosen threshold. The recalculated primary interval includes zero and extends to values on either side. Thus, it does not isolate a single direction for the unadjusted group difference. The registry does not report a confidence interval for the sponsor’s own analysis.

Confidence intervals depend on the analysis method and its assumptions. They do not describe the range of individual participants’ scores, and they are not a guarantee that the true effect lies within the particular interval. The posted interval is attached to the simple recalculation, not the sponsor’s reported result. Because the two results conflict, the interval cannot be used to fill in missing information about the sponsor analysis.

Why might a recalculation differ from a trial analysis?

In general, group summaries and a trial analysis can differ if they use different endpoint definitions, analysis populations, adjustments, or methods. These examples explain why a discrepancy can occur; the registry record does not say which, if any, accounts for this trial’s difference. Baseline adjustment, missing-data handling, and the exact analysis population are not reported. It would be inappropriate to infer a particular explanation from the conflict alone.

The trial’s posted summary statistics support an unadjusted comparison, whereas the sponsor’s report is a separate registered analysis. Since the record flags a discrepancy, the sponsor’s own analysis takes precedence. At the same time, its sparse reporting limits independent evaluation. Reporting the two analyses distinctly preserves what each says without treating the recalculation as a correction to the trial’s analysis.

11. Confidence Intervals and Precision

The unadjusted primary estimate is a mean difference of 0.14. Its recalculated confidence interval spans values below and above zero, and the unadjusted p-value is 0.674. In practical statistical terms, the interval does not precisely settle the direction of the difference: it is compatible with a modest difference favoring either numerical direction, as well as with little or no difference. The registry’s reported analysis has no confidence interval listed.

A confidence interval is more informative than a point estimate alone because it displays the uncertainty associated with the estimate. A narrow interval would indicate greater precision for the estimated group difference, while a wide interval would indicate less precision. The interval does not show the spread of outcomes among individual participants; that is described separately by the arm standard deviations. Nor does inclusion of zero prove there is no effect.

Precision must be considered alongside the discrepancy between the sponsor analysis and the summary-statistic recalculation. The recalculated interval belongs to the unadjusted contrast, not to the sponsor’s one-sided t-test. It cannot be used to infer the uncertainty of the sponsor result. The registry record does not report the sponsor analysis’s confidence interval, its test-statistic details, or enough information to reconcile the contrasting conclusions.

The reported arm means and standard deviations provide a limited view of the data. Details such as individual score distributions, baseline measurements, missing observations, and analysis population are not reported in the registry record. Those omissions limit assessment of whether the recalculated interval is a good representation of uncertainty for the intended change-from-baseline question.

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 primary sample-size figures are planning illustrations based on the observed effect, not the trial’s original design assumptions. For a two-arm continuous outcome, the listed figures are participants per arm, not total participants. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. The original sample-size justification is not reported in the registry record.

The 80% power column gives the planned number of participants per arm under those assumptions for a design with an 80% chance of detecting the specified effect if that effect were the true one. The 90% power column gives the corresponding planning number for a 90% chance. These are design probabilities under assumed conditions, not guarantees about a future study’s result. This is not observed power.

For planning at 100% of the observed primary effect, the illustration lists 3,320 participants per arm for 80% power and 4,444 participants per arm for 90% power. For planning at 75% of the observed effect, it lists 5,901 and 7,900 participants per arm, respectively. For planning at 50% of the observed effect, it lists 13,277 and 17,774 participants per arm, respectively. Smaller effects require more participants to detect under otherwise unchanged assumptions, which is why the listed requirements increase as the target fraction decreases.

These figures should not be read as evidence that the trial had those numbers, or that its original design was based on the observed contrast. They are sensitive to the observed estimate, which is itself small and uncertain, and they inherit the limitations of the recalculation. The reported sponsor analysis differs from that recalculation. The planning illustration therefore helps show how sample requirements depend on an assumed effect size; it does not resolve the discrepancy or establish what effect future researchers should expect.

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 = 0.140; pooled standard deviation σ = 2.036.
2. n = 2 × (1.96 + 0.842)² × 2.036² / 0.140² = 3,319.2, rounded up to 3,320 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 <- 0.140000000000001                      # observed difference in means
sigma <- 2.03574310756539                     # 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(803400)
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 = 3,320 (80% power), 4,444 (90% power)
 75% of observed effect: n per arm = 5,901 (80% power), 7,900 (90% power)
 50% of observed effect: n per arm = 13,277 (80% power), 17,774 (90% power)
power.t.test: 3320.1 
Simulated power at n = 3,320 per arm: 0.805 (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. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary analysis as a one-sided t-test of mean difference in final values, with a result value of 1 and p < 0.001. It does not list a confidence interval for that result. The separate unadjusted recalculation from posted arm summaries gives a mean difference of 0.14 and p = 0.674, with a confidence interval that crosses zero. These results are discrepant, and the record does not explain why.

The analyses may not be estimating exactly the same quantity: the primary outcome is titled as change from baseline, whereas the sponsor analysis is labeled as a difference in final values. That wording raises an interpretive question but does not establish the reason for the conflicting results. The record does not report enough information about endpoint coding, baseline adjustment, participant inclusion, missing data, or test direction to reproduce or reconcile the sponsor analysis.

Because the discrepancy flag is true, the sponsor’s own analysis takes precedence over the recalculation. This does not remove the reporting limitation: the sparse description makes it difficult to assess the sponsor result independently. The recalculated contrast is best treated as a check on the posted means and dispersions, not as a substitute for the trial analysis or as proof that the sponsor analysis is incorrect.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when statistical tests are conducted for more than one outcome, comparison, or analysis. The more tests considered, the greater the chance that at least one result appears notable even when the underlying effects are small or absent. The registry lists a primary outcome and two secondary outcomes, but it does not report a testing hierarchy, multiplicity adjustment, or strategy for interpreting secondary analyses. Consequently, the secondary p-values are unadjusted and should not be read as though they were the only tests conducted.

The registry record reports one primary analysis as a one-sided t-test. It does not state whether this was prespecified in a protocol or statistical analysis plan, how the direction was chosen, or whether other primary analyses were considered. The original statistical plan, including any handling of multiple looks or outcomes, is not reported in the registry record. Interim analyses are also not reported in the registry record; their absence from the record cannot establish whether they occurred.

Missing-data handling and analysis populations are likewise not described. The record does not state whether the primary analysis included all randomized participants, only participants with outcome measurements, or another defined group. It does not report how missing baseline or endpoint values were handled, or whether any imputation or sensitivity analyses were used. These details matter because exclusions and missingness can affect both the estimated contrast and its uncertainty.

There is also an outcome-definition issue: the primary title describes change from baseline, but the sponsor result is labeled as a difference in final values. The registry does not clarify the relationship between those descriptions. Along with the discrepancy between the reported sponsor result and the simple recalculation, these omissions constrain independent interpretation. They do not establish that the analyses were inappropriate; they show that the registry record does not contain enough detail to evaluate key choices.

16. 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 lists zero serious adverse events among the 75 participants at risk in the alprazolam arm and zero among the 75 at risk in the alprazolam-plus-aerobic-exercise arm. No serious adverse-event terms are listed. These are the serious-event figures recorded for the trial; they do not establish that no adverse experiences of any kind occurred.

The registry separately lists other adverse events, but those are not serious adverse events and should not be combined with the serious-event figures. The record does not report deaths for either group. That information is not reported in the registry record, so no conclusion about deaths can be drawn from the blank entries.

Safety counts need context, including how events were defined, collected, and attributed, and how long participants were followed. Those details are not reported in the registry record. Zero recorded serious events in these groups should therefore be read narrowly as the posted count, not as proof that serious harms are impossible or that the plans have equivalent safety.

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

The primary posted summaries describe similar group means for the Hamilton Anxiety Rating Scale change-from-baseline endpoint at 12 weeks. The unadjusted recalculation estimates a mean difference of 0.14, with a confidence interval that crosses zero and an unadjusted p-value of 0.674. Taken on its own, that calculation does not provide clear evidence of a difference between the group means. It also does not prove that the treatment plans are equivalent.

The registry’s own analysis reports a one-sided t-test with p < 0.001 and a result value of 1. This conflicts with the simple recalculation, and the registry record does not supply enough methodological detail to explain the contrast. The sponsor’s analysis takes precedence, but the lack of a confidence interval and the ambiguity between the endpoint’s change-from-baseline wording and the analysis’s final-values wording limit independent assessment.

The findings do not establish that adding aerobic exercise does or does not improve panic disorder symptoms. A registered outcome comparison is not, by itself, a complete assessment of clinical benefit, safety, or suitability for an individual. The record does not report the exercise regimen, alprazolam dosing, detailed eligibility criteria, adherence, or participant-level outcome distributions. Nor does it provide the information needed to evaluate how missing outcomes were handled.

The secondary outcomes add context but are subject to the same reporting limitations and to the interpretive problem of multiple unadjusted comparisons. They should not be treated as a substitute for a clearly specified and fully reported primary analysis. The narrow safety entry of zero recorded serious events likewise cannot establish an absence of risk.

The most defensible reading is therefore cautious: the posted primary group summaries are close, while the sponsor’s reported statistical test reaches a different conclusion. The registry does not reconcile them. The numerical record supports describing this conflict and the limits of the available precision, rather than making a categorical claim about treatment effect.

18. Why This Trial Matters Statistically

This trial illustrates why registry results need to be read at more than one level. The arm means and standard deviations permit a simple, transparent comparison, but the sponsor’s reported test reaches a markedly different conclusion. Without a clear account of the endpoint, analysis population, and statistical method, readers cannot determine from the registry record why those results diverge.

It also demonstrates that a p-value alone is not a measure of effect size or precision. The unadjusted recalculation reports an estimate and an interval that spans both directions, whereas the sponsor result is presented without a confidence interval. Those forms of reporting answer different parts of the interpretive question: the point estimate describes the observed contrast, the interval conveys uncertainty, and the p-value evaluates compatibility with a specified null under a test’s assumptions.

The distinction between change from baseline and final values is not merely wording. It can affect what quantity a comparison represents. Clear endpoint definitions and analysis descriptions are essential for readers to understand whether two reported results are comparable. In this record, that distinction remains unresolved.

Finally, the sample-size illustrations show how planning requirements depend on the effect assumed for a future study. They are not evidence about the original design or a measure of how well this trial was powered. Read alongside the missing multiplicity, missing-data, and analysis-population details, they underscore the importance of prespecified methods and transparent reporting for reliable interpretation.

19. 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 information recorded for this trial. The most consequential is the conflict between the sponsor’s reported one-sided t-test and the unadjusted recalculation from the arm summaries. The record does not explain whether the analyses used different endpoint definitions, populations, or methods. It also does not report a confidence interval for the sponsor result.

The primary outcome title refers to change from baseline, while the sponsor analysis is labeled as a difference in final values. The exact change-score definition and treatment of baseline are not reported. Without this information, it is difficult to determine whether the posted arm summaries and the sponsor analysis address the same estimand. The reported lack of masking is another design feature that may be relevant when interpreting subjective symptom ratings; the record does not say whether outcome assessors were masked separately.

Further trial details are absent from the registry record, including eligibility criteria, participant characteristics, intervention duration and schedule, alprazolam dosing, adherence, withdrawals, and follow-up completeness. The analysis population, missing-data methods, and sensitivity analyses are not reported. The original sample-size justification, prespecified statistical plan, interim analyses, and multiplicity approach are also not reported.

Safety reporting is limited to the posted counts. The registry does not provide death counts, serious-event descriptions, event definitions, or sufficient follow-up detail to interpret the absence of recorded serious events. The secondary analyses are unadjusted, and the record does not explain their role in an outcome-testing hierarchy. These limitations do not demonstrate that the trial was conducted improperly; they constrain what can be concluded from its registry record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Efficacy of Aerobic Exercise Added to Alprazolam in Panic Disorder Treatment — NCT00803400.
• Registry record last updated 2021-08-19; status last verified 2021-07.
• Results first posted 2008-12-05.
• 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.

23. Record Summary

NCT00803400 is a completed, randomized, parallel-group phase 4 trial sponsored by the University of Buenos Aires. It compared alprazolam alone with alprazolam plus aerobic exercise in patients with panic disorder. The primary outcome was change from baseline in Hamilton Anxiety Rating Scale scores at 12 weeks.

The posted primary means are 22.59 and 22.73, respectively. An unadjusted recalculation gives a mean difference of 0.14 and p = 0.674, while the registry reports a one-sided t-test with p < 0.001. The record does not explain this discrepancy, so the sponsor’s own analysis takes precedence, with substantial limits on independent interpretation. The primary confidence interval from the recalculation crosses zero. Two secondary outcomes are listed, and the registry records zero serious adverse events in each arm. Key information on endpoint definition, missing data, analysis populations, and the original statistical plan is not reported in the registry record.