Randomized, Placebo-controlled Trial of Lubiprostone as a Preparation for Capsule Endoscopy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Randomized, Placebo-controlled Trial of Lubiprostone as a Preparation for Capsule Endoscopy (NCT00746395), a randomized phase 4 study. The primary outcome is Complete Small Bowel Transit.

2. Clinical Question

3. Trial Design

The registry describes a randomized, double-masked, parallel-group, placebo-controlled Phase 4 trial sponsored by the University of South Alabama. Its stated purpose was to compare lubiprostone and placebo for cleansing and propulsion in preparation for capsule endoscopy. The study is listed as completed. Its start is recorded as 2008-04, and its primary completion as 2008-09.

One arm received lubiprostone 24mcg as a single oral dose before capsule endoscopy. The other received a matched single oral dose of placebo, described as a sugar pill. Random allocation and double masking are recorded, but the method used to generate the allocation sequence, the concealment procedure, and the masking arrangements for participants, clinicians, or assessors are not reported in the registry record. The intended parallel structure indicates separate groups receiving their assigned intervention, rather than a crossover comparison.

The registry lists enrollment as 45. For complete small-bowel transit, the reported arm denominators are 20 for lubiprostone and 20 for placebo. For the secondary transit-time outcome, the denominators are 15 and 19, respectively. Reasons for the differences in these outcome denominators, participant flow after enrollment, and the analysis population definitions are not reported in the registry record. The registry does not report whether all enrolled participants were randomized or included in each outcome analysis.

The primary outcome was the percentage of subjects with capsule passage through the small bowel within 8 hours. Small-bowel transit time in minutes during the 8-hour test was listed as a secondary outcome. The record lists two outcome measures and no reported analyses. The original protocol, planned statistical procedures, sample-size justification, and any interim-analysis plan are not reported in the registry record. These omissions limit how confidently the posted summaries can be connected to the full design and conduct of the trial.

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: 45 participants recruited and screened, 1 excluded, 4 withdrew from study.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Placebo 95%, lubiprostone 75%

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 Complete Small Bowel Transit, measured over 8 hours.

The primary endpoint was complete small-bowel transit, measured as the percentage of subjects whose capsule passed through the small bowel within 8 hours. It is a binary outcome at the participant level: each person either has recorded passage within that window or does not. The registry reports the outcome as a percentage, rather than as a duration or an average transit time.

This kind of endpoint addresses whether passage occurred by a specified time. It is distinct from asking how many minutes transit took among participants for whom a duration was available. The registry lists small-bowel transit time in minutes as a secondary outcome, so the two measures describe related but non-identical aspects of capsule progression. A participant may contribute to a passage proportion even when a transit-time value is unavailable; the registry does not explain how such cases were handled.

The outcome is relevant to the stated study purpose because the trial compares preparations intended to affect cleansing and propulsion before capsule endoscopy. However, the registry record does not provide a detailed endpoint definition beyond percentage of subjects with passage, or describe how passage was assessed, how incomplete tests were classified, or whether the endpoint was assessed by masked reviewers. Those details matter when interpreting a binary result, because the classification procedure determines who is counted as having achieved the event.

7. Results Posted in the Registry

• Sugar Pill: 95.0% (19/20) versus 75.0% (15/20) on control; risk difference 20.0 percentage points (95% CI -1.2 to 41.2), risk ratio 1.27 (0.96–1.66); unadjusted two-proportion z-test p = 0.077.

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.

Small Bowel Transit

• 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 errors.
• Result:
  • Sugar Pill: mean 218.90 versus 188.10 on control; difference 30.80 (95% CI -188.72 to 250.32), standardized effect d = 0.09; z-test p = 0.783.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Sugar Pill and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists one secondary outcome, small-bowel transit time in minutes. It adds information about timing to the primary outcome’s focus on passage by 8 hours, so it is related to the primary result but does not measure the same event. A mean duration and a proportion achieving passage within a fixed window can give different pictures of capsule progression. The registry does not report how the two outcomes were intended to be combined or prioritized beyond identifying one as secondary.

The secondary estimate is imprecise, with a broad confidence interval that includes zero, and its unadjusted p value is 0.783. Its denominators differ from those of the primary endpoint. These features mean that it should be interpreted as a limited, exploratory complement to the primary outcome rather than as an independent confirmation of it. The registry does not report why transit-time values are absent for some participants or how those cases were treated.

Secondary results carry less weight when many outcomes or comparisons may be examined without a prespecified strategy for controlling false-positive findings. Testing multiple outcomes increases the chance that at least one appears unusual by chance. The record lists two outcome measures, but does not report a multiplicity adjustment, a hierarchy among secondary comparisons, or a planned interpretation rule. The posted secondary p value is unadjusted, so it does not account for any broader set of comparisons that may have been considered. No additional secondary endpoints or reported analyses are listed in the registry record.

Across the outcomes, the registry does not provide precise evidence that resolves the uncertainty in the primary comparison. The secondary measure is conceptually relevant, but it cannot repair limitations in the primary endpoint’s precision or establish a distinct conclusion on its own. Read together, the outcomes describe observed summaries in this trial; they do not provide a documented, multiplicity-controlled analysis of a prespecified set of endpoints.

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

• Small Bowel Transit

9. Statistical Interpretation

10. Statistical Methods Explained

The primary measure is a binary outcome: passage through the small bowel within 8 hours is counted as an event, and the group result is expressed as a percentage. For each group, the percentage is based on the number with passage divided by the number contributing to that outcome. The registry reports 75% for lubiprostone and 95% for placebo, with 20 participants in each denominator. A percentage gives an accessible description of the observed event frequency, but it does not by itself quantify uncertainty about the difference between groups.

What does a risk difference describe?

A risk difference subtracts one group’s event proportion from the other group’s event proportion, using the specified comparison direction. Here the comparison is placebo relative to lubiprostone, and the reported risk difference is 0.2. A risk difference is expressed on the same absolute-proportion scale as the event rates. Its confidence interval, from -0.013 to 0.412, shows the range of values compatible with the data under the interval method used. Because the interval crosses zero, it includes both no difference and values on either side of no difference. The registry does not report which interval procedure or inferential test was part of the original analysis plan.

How do relative measures differ?

A risk ratio compares event proportions by division, while an odds ratio compares the odds of the event between groups. Both express a relative contrast rather than an absolute difference. They can look numerically quite different from a risk difference, and the odds ratio can be especially difficult to interpret as an event probability. The registry reports a risk ratio of 1.267 with an interval from 0.965 to 1.663, and an odds ratio of 6.333 with an interval from 0.667 to 60.16. These wide intervals signal that the relative effect estimates are uncertain. The confidence intervals for relative measures are interpreted against their no-association value, unlike a risk difference, whose no-difference value is zero.

What does a p value contribute?

The unadjusted p value for the primary comparison is 0.077. A p value describes how unusual data at least as discrepant as those observed would be under a specified null model and its assumptions. It is not a measure of effect size, a probability that the null hypothesis is true, or an assessment of whether a difference matters to patients or procedure quality. Its interpretation depends on the analysis having been selected appropriately and on the assumptions being reasonable. The registry does not report the trial’s planned statistical test, its significance threshold, or an analysis plan, so the posted p value should be read as an unadjusted recalculation rather than as a documented prespecified trial result.

Why does the secondary measure use different methods?

Small-bowel transit time is continuous, reported in minutes as a mean with a standard error. The group means are 188.1 and 218.9, and the posted mean difference for placebo relative to lubiprostone is 30.8. A mean difference describes a contrast in average values, rather than the contrast in the fraction passing by a fixed time. The confidence interval extends from -188.7 to 250.3, and the unadjusted p value is 0.783. The standard error describes uncertainty in an estimated mean; it is not the same as the spread of individual participant times. The record does not describe distributional checks, transformations, or handling of observations that reached the end of the test without a transit-time value.

The number of observations differs between the primary and secondary outcomes: the transit-time outcome has denominators of 15 and 19. Different denominators can arise for a variety of reasons, but the specific reasons and the missing-data procedures are not reported in the registry record. Consequently, the secondary mean comparison should not be treated as if it were based on exactly the same outcome set as the primary percentages.

The reported inferential quantities are unadjusted recalculations from posted summary statistics. Such calculations can describe the summaries but cannot reconstruct every feature of an original analysis, including covariate adjustment, stratification, or a prespecified model. None of those procedures is reported in the registry record. The discrepancy flag is false, but no sponsor-reported analyses are listed. Accordingly, the calculations do not substitute for a documented trial analysis plan or an analysis using participant-level data.

Over-dispersion is a general statistical concern when observed variability is greater than a model assumes. In a binary outcome, dependence among participants or unaccounted differences between them can make a simple model understate uncertainty. For a continuous outcome, a model that does not reflect the observed distribution can also misstate precision. The registry does not report model diagnostics or evidence of over-dispersion in this trial, so this is a general consideration rather than a trial-specific finding.

11. Confidence Intervals and Precision

Precision concerns how tightly an estimate is located by its uncertainty interval. The primary risk-difference estimate is 0.2, with a confidence interval from -0.013 to 0.412. This interval is broad relative to the point estimate and spans zero. It therefore does not identify a single direction or a narrow range of plausible difference values. The group percentages are useful descriptions of the observed participants, but the interval makes clear that they should not be treated as exact estimates of the underlying group outcomes.

The relative estimates are also imprecise. The risk ratio is 1.267, with an interval from 0.965 to 1.663; the odds ratio is 6.333, with an interval from 0.667 to 60.16. In each case, the interval spans the no-association value for that measure. The especially wide odds-ratio interval indicates that the data allow a broad range of relative effects. Small denominators and the distribution of events can contribute to this type of uncertainty, although the registry does not provide a precision analysis beyond the reported intervals.

For the secondary mean difference, the estimate is 30.8 minutes, and the confidence interval extends from -188.7 to 250.3. This range includes zero and permits a wide span of possible differences. Its width should be considered alongside the secondary denominators of 15 and 19. The registry reports standard errors for the group means but does not provide participant-level observations or further detail about the interval method.

A confidence interval is not a guarantee that the true value lies within its endpoints, nor does it assign equal plausibility to every value in the range. It is a procedure whose long-run coverage depends on its assumptions. The registry does not report the procedures used in an original analysis, so the posted intervals are best read as uncertainty summaries attached to the unadjusted recalculations, not as documented protocol-specified estimates.

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 for 80% power and participants per arm for 90% power. These are not total event counts. The planning illustration assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It considers detecting the stated fraction of the observed effect, with separate planning values for 100%, 75%, and 50% of that effect. The trial’s own original sample-size assumptions are not reported in the registry record.

The 80% power column describes a planning target: under the stated assumptions, the listed participants per arm would give an 80% chance of detecting the effect used in that calculation if that effect were the true one. The 90% column uses a higher chance of detecting that effect, and therefore requires more participants per arm. Power is a design property under assumptions, not a description of what the completed trial achieved.

Smaller effects require more participants to distinguish them from random variation with the same planned power and significance level. Thus, the entries for 75% and 50% of the observed effect are larger than the entries for the full observed effect. This illustrates how planning requirements rise as the target difference becomes less pronounced. The estimates are illustrative because they start from the observed effect, which is itself uncertain and may not represent the effect expected in a future study.

For the primary binary outcome, the planning values are 49 and 65 participants per arm for 100% of the observed effect, 100 and 133 for 75%, and 250 and 335 for 50%, for the 80% and 90% targets respectively. The secondary continuous-outcome illustration uses participants per arm as well, not total events. These figures are planning illustrations, not observed power. The registry states that the illustration is based on the observed effect and is not the trial’s own design justification.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.750; treatment proportion p₁ = 0.950; average p̄ = 0.850.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5050 = 0.9897.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4848 = 0.4080.
4. n = (0.9897 + 0.4080)² / (0.2000)² = 48.8, rounded up to 49 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
p0 <- 0.75                          # control proportion
p1 <- 0.95                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(746395)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 49 (80% power), 65 (90% power)
 75% of observed effect: n per arm = 100 (80% power), 133 (90% power)
 50% of observed effect: n per arm = 250 (80% power), 335 (90% power)
power.prop.test: 48.8 
Simulated power at n = 49 per arm: 0.847 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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 more than one outcome, comparison, subgroup, or analysis is examined. If many tests are conducted, some may produce apparently notable results by chance even when there is no underlying effect. A prespecified hierarchy or adjustment can help define how results should be interpreted. The registry lists two outcome measures, including one primary outcome and one secondary outcome, but does not report a multiplicity strategy, an adjustment procedure, or a hierarchy governing interpretation of the secondary measure.

The registry lists no reported analyses. The posted p values and intervals are unadjusted recalculations from summary statistics, rather than a documented set of sponsor-reported model results. The original statistical analysis plan, choice of tests, any covariate adjustment, and any interim-analysis plan are not reported in the registry record. It is therefore not possible to determine whether the posted outcomes and calculations fully reflect the analyses planned before results were known.

Missing-data handling is also not described. The primary endpoint denominators are 20 in each arm, while the secondary denominators are 15 and 19. The record does not state why the available denominators differ, whether missing outcomes were related to participant characteristics or capsule passage, or what assumptions were used when observations were unavailable. It also does not state whether any imputation or sensitivity analysis was performed. These omissions matter because analyses based only on observed outcomes can be affected if the likelihood of an outcome being missing is related to the outcome itself.

The analysis populations are not defined. The registry does not say whether the reported results use an intention-to-treat population, a per-protocol population, or another set of participants. It also does not provide a participant flow account that would explain enrollment, randomization, exclusions, or completion for each endpoint. Without those details, the denominators can be reported as stated, but the reasons for inclusion and exclusion cannot be reconstructed.

Randomization and double masking are recorded, but allocation generation, concealment, and masking procedures are not described. These design features can reduce bias when implemented and maintained, but the registry does not provide enough detail to assess their operation. The lack of these methods and analysis details limits assessment of risk of bias; it does not by itself show that bias occurred.

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 serious adverse events for 20 participants at risk in each group, with 0 serious adverse events in the lubiprostone group and 0 in the placebo group. The record lists no serious adverse-event terms. These figures describe what was recorded for the reported groups; they do not establish that no serious events occurred outside the reporting period or that the risks are identical.

Other adverse events are listed for 20 participants at risk in each arm, with 1 affected participant in each group. The record does not provide event terms or further detail about severity, timing, or relationship to treatment. Death counts are not reported in the registry record.

With these denominators, event counts are limited, and the absence of recorded serious events in either group cannot rule out uncommon harms. The registry does not report a detailed safety analysis, follow-up duration for adverse events, or how adverse events were collected. The figures should therefore be read as a brief registry account, not as a comprehensive comparison of safety.

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

The posted primary summaries show complete small-bowel transit within 8 hours in 75% of the lubiprostone group and 95% of the placebo group. The estimated risk difference is 0.2 for placebo relative to lubiprostone, but its confidence interval ranges from -0.013 to 0.412. The interval includes zero and covers a broad range, so the observed percentages do not determine the size or direction of the underlying difference with precision.

The secondary mean transit-time comparison is similarly uncertain. Its estimate is 30.8 minutes for placebo relative to lubiprostone, with a confidence interval from -188.7 to 250.3. That interval includes zero and spans a wide range. The secondary denominators differ from the primary denominators, and the registry does not report reasons for the difference.

These data do not establish that either intervention improves or worsens capsule endoscopy preparation. Nor do they establish equivalence or prove that there is no difference. An imprecise estimate can be compatible with several possibilities, including no difference and effects in either direction. A p value does not replace consideration of effect size, interval width, design, and data completeness.

The trial record is useful for identifying the comparison, outcomes, observed group summaries, and limited adverse-event counts. It does not report a complete statistical plan, analysis population, missing-data approach, endpoint assessment details, or sponsor-reported analyses. Those omissions prevent a full assessment of how the posted results fit the trial’s intended analysis. The findings should be understood as the reported results for this trial, not as definitive evidence applicable to all capsule endoscopy preparations or populations.

17. Why This Trial Matters Statistically

This trial illustrates the distinction between observing different group percentages and estimating a difference precisely. The primary outcome percentages differ descriptively, but the risk-difference interval is wide and crosses zero. Reading the point estimate without the interval would conceal how much uncertainty remains. The same issue appears in the relative estimates, whose intervals span broad ranges.

The comparison also shows why absolute and relative measures answer different questions. A risk difference describes a contrast on the event-proportion scale, while risk ratios and odds ratios describe relative contrasts. Their numerical scales and no-effect values differ, so they should not be read interchangeably. Presenting more than one measure can aid interpretation, but does not create additional independent information from the same participants.

The primary and secondary endpoints capture distinct features of capsule progression: passage by a set time and mean transit time. Their denominators also differ. This makes the registry’s reporting of outcome-specific denominators important for understanding what data contribute to each summary, while the absence of an explanation for the differing denominators limits further interpretation.

Finally, the record distinguishes registry outcome summaries from a complete trial analysis. No analyses are reported, and the original analysis plan and sample-size rationale are not reported. The unadjusted recalculations can help readers understand the posted summaries and their precision, but cannot replace prespecified methods or participant-level analyses. These are general lessons in reading small clinical trials: effect estimates, uncertainty, outcome definitions, denominators, and analysis transparency all matter alongside the randomized design.

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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The primary endpoint is reported as a percentage of subjects with capsule passage, but detailed operational definitions are not reported in the registry record. The record does not explain assessment procedures, classification of incomplete passage, or whether endpoint assessors were masked. These details can affect how consistently the binary outcome is measured.

The registry lists enrollment of 45, while the primary outcome denominators are 20 in each arm. The secondary denominators are 15 and 19. No participant flow or explanation for these denominators is reported. Consequently, it is not possible to determine from the registry record why outcome data were unavailable for some participants or whether exclusions differed in meaningful ways between groups.

The record does not describe eligibility criteria beyond the condition and preparation context, nor does it report baseline characteristics. This limits assessment of how similar the trial participants were to other populations in whom capsule endoscopy preparation may be considered. It also does not report adherence to the assigned single dose, protocol deviations, or co-interventions.

Although randomization and double masking are recorded, the procedures for sequence generation, concealment, and maintaining masking are not reported. The original statistical analysis plan, population definitions, missing-data methods, multiplicity handling, and sample-size justification are also not reported. No interim-analysis plan is reported. The registry lists no reported analyses, which limits comparison between the posted summary statistics and a prespecified sponsor analysis.

The study is listed as completed, but the registry record does not provide a detailed account of the timing and duration of safety follow-up. Serious adverse events are reported as zero in each arm, while deaths are not reported. The small denominators and limited adverse-event detail mean the safety information is descriptive and incomplete. These are limitations in what the registry record documents; they do not demonstrate that the trial was conducted improperly.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Randomized, Placebo-controlled Trial of Lubiprostone as a Preparation for Capsule Endoscopy — NCT00746395.
• Registry record last updated 2020-10-08; status last verified 2020-09.
• Results first posted 2017-01-04.
• 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, double-masked, parallel, placebo-controlled Phase 4 trial sponsored by the University of South Alabama. It lists enrollment of 45 and a study period beginning in 2008-04, with primary completion in 2008-09. The stated purpose was to compare lubiprostone and placebo for cleansing and propulsion before capsule endoscopy.

The primary outcome was complete small-bowel transit within 8 hours. The registry reports 75% for lubiprostone and 95% for placebo, with 20 participants in each arm. The unadjusted risk difference is 0.2, with a confidence interval from -0.013 to 0.412. Small-bowel transit time was listed as a secondary outcome, with outcome denominators of 15 and 19. No analyses are reported in the registry record.

Serious adverse events were recorded for 0 participants in each group, with 20 at risk in each. Other adverse events affected 1 participant in each group. Death counts are not reported in the registry record. The posted estimates are imprecise, and key details of the trial’s analysis plan, missing-data handling, and participant flow are not reported.