Low-Dose Galantamine to Potentiate the Attention-Enhancing Effects of Low-Dose Nicotine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Low-Dose Galantamine to Potentiate the Attention-Enhancing Effects of Low-Dose Nicotine (NCT02420327), a randomized na study. The primary outcome is Spatial Attentional Resource Allocation Task Predictive Trials Reaction Time.

2. Clinical Question

3. Trial Design

The registry record describes NCT02420327 as a completed, randomized, triple-masked study sponsored by the University of Maryland, Baltimore. Its model is listed as single group, and its enrollment is 43. The record gives the study period as 2014-09 to 2017-03 for start and primary completion. Phase is listed as NA. These registry labels describe the recorded design but do not explain the allocation sequence or the masking procedures in detail.

The listed conditions are placebo patch with placebo capsule, placebo patch with galantamine capsule, nicotine patch with placebo capsule, and nicotine patch with galantamine capsule. The summary describes two single exposures to a nicotine patch at 7 mg/24 hrs and two single exposures to 4 mg galantamine. It does not report the order of test conditions, the interval between exposures, or how randomization was implemented. Those details are not reported in the registry record.

The primary outcome population is stated as 27 healthy adult non-smokers, and each of the four posted condition summaries has n = 27. That is not the same as the overall enrollment of 43. The registry record does not explain the difference or specify whether the primary-outcome summaries include all randomized participants, only participants with complete measurements, or another analysis population. The number randomized and the number completing each condition are not reported in the registry record.

The posted comparison estimates are unadjusted mean differences against the double-placebo condition. No registry-reported analyses are listed. There is no posted estimate for the direct nicotine-plus-galantamine versus nicotine-alone contrast or for a treatment interaction. The registry record does not report the original statistical analysis plan, a sample-size justification, or details on interim analyses.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 27 healthy adult non-smokers

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.

Population: This includes 27 study completers and 16 study non-completers.

6. Primary Endpoint

The registry lists the primary outcome as Spatial Attentional Resource Allocation Task Predictive Trials Reaction Time, measured over 45 min.

The primary endpoint is the mean reaction time, in ms, on predictive trials of the Spatial Attentional Resource Allocation Task. On these trials, a central cue predicts where a brief target will appear among four screen locations. The posted measurement timeframe is 45 min. The registry describes the primary outcome as a continuous measure reported as a mean with standard deviation.

Reaction time captures how quickly participants respond to the target, making it a performance measure relevant to a study of attention. As a general statistical interpretation, a lower reaction-time mean represents faster responses, while a higher mean represents slower responses. That interpretation does not on its own establish why reaction times differ, or whether any difference is meaningful in practical terms.

The task's predictive cue is part of the endpoint definition: the measure concerns responses when the location is signaled in advance, not every kind of attention or cognitive performance. The registry description does not provide task reliability information, a threshold for a meaningful change, or details about how individual trial responses were combined into each participant's value. Those details are not reported in the registry record.

For the posted primary comparisons, the double-placebo condition is the reference. The study's stated hypothesis concerns whether galantamine potentiates nicotine, which is a question about the difference between treatment effects across conditions. Comparisons of each condition with double placebo are informative about those individual contrasts, but they do not directly supply the interaction estimate needed to answer the potentiation question.

7. Results Posted in the Registry

• Nicotine Patch and Placebo Capsule: mean 408.00 versus 420.00 on control; difference -12.00 (95% CI -44.65 to 20.65), standardized effect d = -0.20; z-test p = 0.471.
• Placebo Patch and Galantamine Capsule: mean 416.00 versus 420.00 on control; difference -4.00 (95% CI -37.90 to 29.90), standardized effect d = -0.06; z-test p = 0.817.
• Nicotine Patch and Galantamine Capsule: mean 413.00 versus 420.00 on control; difference -7.00 (95% CI -41.42 to 27.42), standardized effect d = -0.11; z-test p = 0.690.

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.

Profile of Mood Scale - Total Mood Disturbance

• 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:
  • Nicotine Patch and Placebo Capsule: mean -0.48 versus -0.32 on control; difference -0.16 (95% CI -0.66 to 0.34), standardized effect d = -0.17; z-test p = 0.534.
  • Placebo Patch and Galantamine Capsule: mean -0.60 versus -0.32 on control; difference -0.28 (95% CI -0.79 to 0.23), standardized effect d = -0.29; z-test p = 0.279.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Nicotine Patch and Placebo Capsule 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 Placebo Patch and Galantamine Capsule and the control. The interval gives the range of effects that remain compatible with the data.

The registry identifies Profile of Mood Scale - Total Mood Disturbance as a secondary outcome. The posted means are -0.32 in double placebo, -0.48 with nicotine and placebo capsule, -0.6 with placebo patch and galantamine, and -0.43 with nicotine plus galantamine. The two posted unadjusted contrasts are against double placebo: the nicotine-only estimate is -0.16, with a 95% confidence interval from -0.664 to 0.344 and p = 0.534; the galantamine-only estimate is -0.28, with a 95% confidence interval from -0.787 to 0.227 and p = 0.279. Both intervals include zero.

Those estimates do not form a consistent basis for a claim about the primary reaction-time outcome. Mood disturbance and reaction time are different measures, with different scales and timeframes: the secondary measure is recorded at 5 min, while the primary task outcome is recorded at 45 min. The registry record does not report a direct analysis linking the two outcomes. The secondary findings therefore provide a separate description, not confirmation of the primary result or a test of the potentiation hypothesis.

The registry lists seven outcome measures, but the record posts one secondary outcome and no reported analyses. The unadjusted secondary comparisons carry less weight because multiple outcomes and comparisons create more opportunities for chance findings, and no multiplicity adjustment is reported. This is a general statistical concern; the registry record does not state what multiplicity strategy, if any, was planned.

The secondary results should be interpreted as exploratory descriptive evidence rather than as a basis for a firm conclusion. Their intervals are broad enough to include zero and differences in either direction. No direct combination-versus-nicotine-only comparison is posted for this secondary measure. The record also does not report how missing secondary measurements were handled or whether the posted set represents all prespecified secondary outcomes.

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

• Profile of Mood Scale - Total Mood Disturbance

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous, and the registry reports condition means and standard deviations. A mean gives the average reaction time in a condition; a standard deviation describes how spread out participant measurements are around that mean. These summaries are useful for describing the observed data, but they do not capture every detail of the underlying participant-level distribution.

What does a mean difference describe?

A mean difference compares the average in one condition with the average in a reference condition. The posted contrasts use double placebo as the reference. A negative estimate means the condition mean is numerically lower than the reference mean; for reaction time, that corresponds to a shorter average response time. The estimate does not by itself indicate whether the observed difference is precise or whether it can be attributed to a specific component of the condition.

The posted estimates are unadjusted comparisons derived from summary statistics. They do not account for covariates or other design features in a reported model. The registry record does not report an analysis model, adjustment variables, participant-level data, or a sponsor-reported statistical analysis for this outcome. The posted p-values are explicitly unadjusted, so they should not be read as accounting for multiple comparisons.

What does the confidence interval add?

A confidence interval describes uncertainty around an estimated effect under the assumptions of its statistical method. It gives a range of values that are reasonably compatible with the data and method; it is not a guarantee that the true effect lies in that particular interval. An interval spanning zero indicates that a zero mean difference is among the values compatible with the estimate. A wide interval indicates less precision than a narrow one. General statistical interpretation does not convert an interval into a probability that a treatment works or does not work.

Each primary confidence interval includes zero, and each extends to values on both sides of zero. Thus, the posted contrasts leave uncertainty about both the direction and size of the difference. The p-values likewise do not provide an effect size: they describe how unusual the data would be under a specified null model and assumptions. The registry record does not report enough about the analysis method to reconstruct a full model-based interpretation of those tests.

Why is the stated hypothesis a different contrast?

Potentiation is a claim that the effect of nicotine changes in the presence of galantamine. In a factorial framing, that question is represented by an interaction: whether the nicotine-versus-placebo contrast differs between galantamine and placebo conditions. Comparisons of each of the three active combinations with double placebo answer separate questions. They do not, on their own, estimate the interaction. The registry record does not report that direct interaction analysis or a direct nicotine-plus-galantamine versus nicotine-alone estimate.

The model is listed as single group, with randomized and triple-masked allocation labels. The registry summary also describes repeated single exposures to nicotine and galantamine. However, the order, sequence, period handling, and within-participant correlation structure are not reported in the registry record. Those details matter because repeated measurements on the same person are not generally independent. Without the analysis plan and participant-level data, the posted summary-based comparisons cannot account for any unreported dependence structure.

What role do sample-size illustrations play?

General power calculations ask how often a specified analysis would detect an effect of a stated size if the assumptions held. The planning illustrations use the observed contrasts as starting points and consider smaller fractions of those effects. They are not evidence about the probability that the original study detected an effect, and they do not establish what the trial was designed to detect. The original design assumptions are not reported in the registry record. The illustrations also rely on stated assumptions, so their figures should be interpreted as planning scenarios rather than forecasts for a different design.

Finally, an absence of reported analyses is not the same as evidence that no analysis was conducted. It means the registry record does not make those results available for interpretation. The posted summaries can describe condition means and simple contrasts, but they cannot replace a prespecified analysis plan, a complete account of the randomized population, or an analysis that directly addresses the study's potentiation hypothesis.

11. Confidence Intervals and Precision

Precision is most directly conveyed by the confidence intervals around the mean differences. For nicotine patch with placebo capsule versus double placebo, the estimate is -12.0 ms and the interval runs from -44.65 to 20.65. For placebo patch with galantamine capsule versus double placebo, the estimate is -4.0 ms and the interval runs from -37.9 to 29.9. For nicotine patch with galantamine capsule versus double placebo, the estimate is -7.0 ms and the interval runs from -41.42 to 27.42.

All three intervals include zero and include both negative and positive differences. They therefore leave substantial uncertainty about the direction of the underlying mean differences. For the nicotine-only contrast, for example, the data are compatible with a lower mean reaction time as well as a higher one. The same general interpretation applies to the other two contrasts. The point estimates are single best estimates from the posted summaries; the intervals show that the estimates should not be read as exact effects.

These intervals do not establish that the conditions are equivalent. Equivalence requires a prespecified margin defining differences small enough to count as practically similar, along with an appropriate analysis. No equivalence margin is reported in the registry record. The record also does not give a threshold for a clinically or practically meaningful change in reaction time. Consequently, it is not possible to determine from these intervals alone whether the range of compatible values is meaningful for performance.

The summary record gives n = 27 in each primary condition, while the overall enrollment is 43. It does not explain the analysis population or the difference between those counts. That uncertainty, together with the lack of a reported analysis model, limits interpretation of precision beyond the intervals attached to the posted contrasts. The intervals characterize uncertainty under the calculations used for those contrasts, not uncertainty from every possible source of bias or missing data.

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 sample-size illustrations translate selected effect sizes into planning counts. For this continuous outcome, the figures are participants per arm, not total events. Each row is framed around detecting a stated fraction of the observed effect: the full observed effect, 75% of the observed effect, or 50% of the observed effect. These are planning scenarios, not counts from the trial.

The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. The original trial's own sample-size assumptions and justification are not reported in the registry record. The power columns describe the number of participants per arm associated with an 80% or 90% chance of detecting the selected effect under those assumptions, if the assumed effect and analysis conditions hold. The higher power target requires more participants than the lower target for a given effect.

Smaller effects are harder to distinguish from random variation, so the illustrations require more participants per arm when planning for a smaller fraction of the observed effect. This is a general feature of statistical planning, not evidence that a larger study would necessarily reproduce the same effect. The observed estimates are themselves uncertain, as reflected by their confidence intervals.

These figures are not observed power. Observed power is not a useful substitute for reading the estimated effects and their uncertainty; the illustrations are prospective planning calculations based on specified assumptions. The plotted curve expresses the same planning relationship across effect sizes and should be read with those assumptions in mind, not as a prediction of outcomes in a future trial.

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 = -12.000; pooled standard deviation σ = 61.205.
2. n = 2 × (1.96 + 0.842)² × 61.205² / -12.000² = 408.4, rounded up to 409 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 <- -12                      # observed difference in means
sigma <- 61.2045749923974                     # 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(2420327)
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 = 409 (80% power), 547 (90% power)
 75% of observed effect: n per arm = 726 (80% power), 972 (90% power)
 50% of observed effect: n per arm = 1,634 (80% power), 2,187 (90% power)
power.t.test: 409.3 
Simulated power at n = 409 per arm: 0.801 (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

Multiplicity arises when several outcomes, treatment contrasts, or analyses are considered. Testing many hypotheses without an adjustment or a prespecified hierarchy can increase the chance of at least one seemingly notable result arising by chance. The registry lists seven outcome measures and posts one secondary outcome. The primary outcome includes three posted comparisons against double placebo, and the secondary outcome includes two posted comparisons. The p-values are unadjusted.

The registry record does not report a multiplicity plan, such as a primary contrast hierarchy, adjustment procedure, or designation of which secondary analyses are confirmatory. It also lists no reported analyses. Therefore, the posted p-values should be treated as unadjusted descriptive evidence, not as results known to control error across all outcomes and comparisons. No inference about a broader family-wise error rate can be made from the record.

Information about missing data is also limited. The overall enrollment is 43, whereas the primary and secondary summaries list n = 27 in each condition. The record does not explain why these counts differ, report the number with missing measurements, describe exclusions, or state whether any imputation was used. It does not report an intention-to-treat or per-protocol analysis population. The extent and handling of missing data are therefore not reported in the registry record.

The listed model is single group, and the record also describes randomized, triple-masked allocation and multiple single exposures. It does not provide enough detail to establish how repeated measurements were analyzed, whether participants contributed to each condition in the same way, or how within-person dependence was handled. These design and analysis details affect interpretation of standard errors and confidence intervals. Their absence does not show that the analysis was inappropriate; it limits what can be verified from the registry record.

Likewise, the original sample-size justification, statistical analysis plan, and interim-analysis information are not reported in the registry record. It is not possible to determine whether the posted contrasts match the trial's prespecified primary analysis or whether other analyses were planned. These omissions are reasons for caution in interpreting the available results, rather than proof that the underlying study lacked prespecified procedures.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events by condition using the number at risk and the number affected. For double placebo, 32 were at risk and 0 were affected by a serious adverse event. For nicotine patch with placebo capsule, 34 were at risk and 0 were affected. For placebo patch with galantamine capsule, 30 were at risk and 0 were affected. For nicotine patch with galantamine capsule, 32 were at risk and 0 were affected. Deaths are recorded as 0 in each condition.

These entries mean that the registry record reports no serious adverse events in the listed groups. They do not establish that the risk is zero, nor do they rule out events that were not captured or reported. The number at risk varies across conditions, and the record does not explain the group counts or how exposure-level reporting relates to the overall enrollment. No serious adverse-event terms are listed.

Serious adverse events are distinct from other adverse events. The registry also records other adverse events in the groups, but those counts should not be conflated with the serious-event figures. Safety counts are descriptive and do not provide a comparative risk analysis. Further details about event definitions, monitoring, attribution, or follow-up are not reported in the registry record.

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

The posted primary data describe average reaction times in four test conditions among healthy adult non-smokers. Relative to double placebo, the three estimated mean differences are all negative, meaning that each active condition's observed mean is numerically shorter. Each confidence interval, however, includes zero and extends to values on both sides. The estimates therefore do not precisely establish the direction or size of a difference.

These results do not demonstrate that nicotine, galantamine, or their combination does or does not affect attention. A confidence interval that includes zero is not proof of no effect, and an unadjusted p-value is not a measure of the probability that a hypothesis is true. The posted summaries leave uncertainty about effects that could be relevant in either direction. No threshold for a meaningful reaction-time difference is reported.

The study's stated hypothesis is specifically about potentiation: whether galantamine enhances the attention-related effect of nicotine. That requires assessing whether the nicotine effect changes when galantamine is present. The registry record does not report that interaction or a direct nicotine-plus-galantamine versus nicotine-alone analysis. The separate contrasts against double placebo cannot answer that question on their own.

The population and setting also define the scope of the posted evidence. The primary outcome is described for healthy adult non-smokers and concerns predictive trials in a particular attention task. The registry does not provide results that establish what would happen in other populations, with different doses, or on outcomes beyond those measured. The study summary describes the work as proof of principle; that description does not remove the uncertainty in the posted estimates.

The record's missing details on analysis populations, missing data, and the original statistical plan add limits to interpretation. The results are best read as descriptive condition summaries and uncertain unadjusted contrasts, not as a definitive test of the study's central hypothesis or as a clinical recommendation.

17. Why This Trial Matters Statistically

This trial is statistically interesting because its stated hypothesis concerns potentiation, while the posted primary comparisons are each against double placebo. The distinction matters: evidence that a combination differs from placebo is not, by itself, evidence that the combination has a greater effect than nicotine alone. A direct interaction contrast is needed to address whether the presence of galantamine changes nicotine's effect. The registry record does not report such an estimate.

The case also illustrates why estimates and intervals are more informative than a binary reading of p-values. The primary estimates point toward shorter mean reaction times, but the confidence intervals are wide enough to include zero and differences in the opposite direction. That pattern conveys uncertainty, not proof of absence and not proof of benefit. The p-values are unadjusted and do not replace the effect estimates or their intervals.

The difference between overall enrollment and the n = 27 condition summaries highlights the importance of knowing who contributed data to an analysis. Without an explanation of those counts, the reader cannot determine how the posted summaries relate to all enrolled participants. Likewise, the absence of a reported model leaves uncertainty about how the randomized, repeated-exposure design was reflected in the analysis.

Finally, the sample-size illustrations show how planning depends on the target effect and assumptions, but they do not reveal the original design rationale. Taken together, the record is a useful example of separating a stated scientific question from the contrasts that are actually posted, and of distinguishing descriptive evidence from a direct test of a hypothesis.

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.

The main limitation specific to interpretation of this trial is the mismatch between the stated potentiation hypothesis and the posted primary contrasts. The estimates compare each active condition with double placebo, but no direct combination-versus-nicotine-only estimate or interaction analysis is reported. This leaves the central comparative question unresolved by the registry results.

The primary outcome summaries report n = 27 for each condition, while overall enrollment is 43. The reason for the difference is not reported in the registry record. Without a participant flow account or a definition of the analysis population, it is not possible to assess how complete the posted summaries are or how exclusions and missing measurements may have affected them.

The registry labels the study randomized and triple-masked and lists a single-group model, while the study summary describes multiple single exposures. The order of conditions, sequence allocation, timing between exposures, and approach to repeated measurements are not reported. These are important for judging whether condition comparisons account for within-participant dependence, period effects, or other design features.

There is no reported statistical analysis plan, analysis model, multiplicity strategy, or original sample-size justification. The primary and secondary p-values are unadjusted, and the record lists seven outcome measures but posts one secondary outcome. The absence of these details makes it difficult to distinguish confirmatory analyses from exploratory ones.

The population is limited in the record to healthy adult non-smokers, and the primary outcome is a task-specific reaction-time measure. The registry does not report a threshold for meaningful change or establish how the task outcome relates to broader functioning. These limitations constrain interpretation of the results and the range of conclusions that can be drawn from them.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Low-Dose Galantamine to Potentiate the Attention-Enhancing Effects of Low-Dose Nicotine — NCT02420327.
• Registry record last updated 2019-11-04; status last verified 2019-10.
• Results first posted 2018-08-17.
• 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

NCT02420327 is a completed randomized, triple-masked study sponsored by the University of Maryland, Baltimore. The registry lists a single-group model and enrollment of 43. Its stated aim was to test whether 4 mg galantamine could potentiate attention-related effects of a 7 mg/24 hrs nicotine patch in healthy non-smokers.

The primary posted outcome is reaction time on predictive trials of a spatial attention task, measured at 45 min. The condition summaries list n = 27 each. Three unadjusted mean differences versus double placebo are posted; all three confidence intervals include zero. The record does not report a direct test of potentiation or a registry-reported analysis.

One secondary outcome, Profile of Mood Scale - Total Mood Disturbance, is posted. The record lists seven outcome measures overall and no reported analyses. It reports no serious adverse events or deaths in the listed conditions. Details about the analysis population, missing data, multiplicity, and the original sample-size plan are not reported in the registry record.