Management Of Pain After Cesarean Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Management Of Pain After Cesarean Trial (NCT03929640), a randomized phase 3 study. The primary outcome is Pain Score.

2. Clinical Question

3. Trial Design

The registry identifies NCT03929640 as a randomized, parallel-group Phase 3 trial sponsored by Milton S. Hershey Medical Center. It lists the trial status as terminated, an enrollment of 49, a start date of 2019-08-05, and a primary completion date of 2020-03-14. The registry record does not report why the trial was terminated, and the status alone does not establish the reason or the effect of termination on the results.

The planned comparison was scheduled oral ibuprofen 600 mg plus acetaminophen 650 mg every 6 hours versus scheduled oral ibuprofen 600 mg plus placebo every 6 hours. The registry lists randomization and a parallel model. Its masking field says triple, while the brief summary describes a double-blinded trial. The registry record does not reconcile these descriptions, so the masking arrangement cannot be characterized more precisely from the record.

The primary outcome was pain score on post-operative day 2, with measurement mid-day from 12 PM to 4 PM. The brief summary also describes recording opiate consumption and pain scores during hospitalization, and surveying participants at one and two weeks about opiate consumption and quality of life. The posted secondary outcome list includes opiate consumption in hospital and four WHOQOL-BREF domains. Numerical secondary results are posted for Domain 1, Domain 2 and Domain 3; numerical results for the other listed secondary outcomes are not reported in the registry record.

The record does not report the original sample-size justification, the intended analysis population, an allocation ratio, or a detailed statistical analysis plan. It also does not report interim analyses. These omissions mean that the posted summaries can be described, but their relation to the original planned analysis cannot be fully assessed.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Participants having a post-op day 2 (mid-day) pain score in their charts.

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: Eligible subjects who received study drug

6. Primary Endpoint

The registry lists the primary outcome as Pain Score, measured over Post-operative day 2, corresponding to 2 days after cesarean section surgery (day of surgery is considered post-operative day 0). Measurement taken mid-day (12 PM - 4 PM).

The primary endpoint is a continuous pain score reported by the participant on a scale from 0, indicating no pain, to 10, indicating the most severe pain possible. The score was recorded on post-operative day 2, defined as two days after cesarean section surgery, with the day of surgery considered post-operative day 0. The measurement window was mid-day, from 12 PM to 4 PM. The endpoint population is described as participants having a post-operative day 2 mid-day pain score in their charts.

A participant-reported score captures the pain the participant experiences rather than relying on an observer to infer it. Comparing group means is a way to describe the average score in each randomized arm and the estimated average difference between arms. The scale's endpoints give the values an interpretable direction: higher values indicate worse reported pain. The mean difference is therefore expressed in score points, with a negative estimate indicating a lower average in the ibuprofen-and-acetaminophen arm relative to the ibuprofen-and-placebo arm.

A mean does not describe every participant's experience, and it can conceal variation within each group. The standard deviations are reported alongside the means to describe that spread. The registry record does not report a threshold for a clinically important difference on this scale, so the posted estimate cannot be classified against such a threshold from this record alone.

7. Results Posted in the Registry

• Ibuprofen and Acetaminophen: mean 3.30 versus 3.50 on control; difference -0.20 (95% CI -1.78 to 1.38), standardized effect d = -0.09; z-test p = 0.804.

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.

WHOQOL-BREF Score, Domain 1

• 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:
  • Ibuprofen and Acetaminophen: mean 16.20 versus 15.60 on control; difference 0.60 (95% CI -1.05 to 2.25), standardized effect d = 0.24; z-test p = 0.475.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ibuprofen and Acetaminophen and the control. The interval gives the range of effects that remain compatible with the data.

WHOQOL-BREF Score, Domain 2

• 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:
  • Ibuprofen and Acetaminophen: mean 16.40 versus 15.60 on control; difference 0.80 (95% CI -0.78 to 2.38), standardized effect d = 0.35; z-test p = 0.321.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ibuprofen and Acetaminophen and the control. The interval gives the range of effects that remain compatible with the data.

WHOQOL-BREF Score, Domain 3

• 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:
  • Ibuprofen and Acetaminophen: mean 17.10 versus 15.40 on control; difference 1.70 (95% CI -0.07 to 3.47), standardized effect d = 0.65; z-test p = 0.060.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ibuprofen and Acetaminophen and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists five secondary outcomes, including opiate consumption in hospital and the four WHOQOL-BREF domains. Numerical results are posted for Domains 1, 2 and 3 at post-operative day 14. Numerical results for in-hospital opiate consumption and Domain 4 are not reported in the registry record. The secondary results therefore give a partial account of the outcomes named in the record.

Across the three posted domains, the estimated mean differences favor higher scores in the ibuprofen-and-acetaminophen arm, while their intervals include zero. This is a directional pattern in the posted estimates, not a definitive finding that the groups differ. The primary pain-score estimate is close to zero and also has an interval spanning zero. The outcome measures concern different constructs and times, so their estimates should not be treated as interchangeable or as direct confirmation of one another.

Secondary comparisons are usually less decisive when multiple outcomes are examined, especially if the analysis plan and multiplicity handling are unknown. When many outcomes or comparisons are considered, the chance of observing an apparently notable result by chance can increase. Adjustment methods and a prespecified hierarchy can address this issue, but such methods are not reported in the registry record. The secondary p-values are unadjusted, and no reported analyses are listed for the secondary outcomes.

Accordingly, the secondary data are best treated as exploratory descriptions of the posted results. Their direction may help frame questions for further study, but the record does not establish a prespecified confirmatory interpretation, complete outcome reporting, or adjustment across outcomes. The absence of numerical results for some listed outcomes also means that the pattern cannot be assessed across the full secondary outcome set.

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

• Opiate Consumption in Hospital
• WHOQOL-BREF Score, Domain 1
• WHOQOL-BREF Score, Domain 2
• WHOQOL-BREF Score, Domain 3
• WHOQOL-BREF Score, Domain 4

9. Statistical Interpretation

10. Statistical Methods Explained

The primary comparison concerns a continuous outcome: a pain score on a bounded scale. For a continuous measure, a group mean describes the average observed value, while the standard deviation describes how much individual observations vary around that average. The posted means are 3.5 for ibuprofen and placebo and 3.3 for ibuprofen and acetaminophen; the standard deviations are 2.3 and 2.4, respectively. These summaries do not imply that each participant had a score close to the group mean. Individual scores may differ, and the registry record does not provide their distribution.

What does a mean difference express?

The mean difference is the average in the combination arm minus the average in the comparator arm. The posted estimate is -0.2. Under this direction convention, a negative value means the observed average was lower in the combination arm. Because lower scores on this scale indicate less reported pain, the point estimate points toward a lower average score in that arm. An estimate is not a guarantee of the true difference: it is calculated from the observed participants and is subject to sampling variation and possible limitations in the data.

The interval from -1.78 to 1.38 describes a range of differences compatible with the data under the method used to construct the interval. Its exact confidence level and construction details are not reported in the registry record. The interval extends below and above zero, so the posted data do not clearly distinguish a difference in one direction from a difference in the other. An interval should be read together with the point estimate: the estimate gives a central summary, while the interval conveys uncertainty around it.

What does the p-value tell the reader?

The unadjusted p-value is 0.804. In general, a p-value measures how unusual data at least as extreme as those observed would be under a stated null model and its assumptions. It is not the probability that the null model is true, nor does it measure the clinical importance of a difference. A large p-value does not establish equivalence. Equivalence requires a defined range of differences considered acceptably small and an analysis designed to assess that question; neither is reported in the registry record.

The comparison is described as unadjusted. In general, an unadjusted comparison uses the posted group summaries without adjustment for other participant characteristics or covariates. That may be a reasonable descriptive comparison, but it does not establish that an adjusted analysis would give the same result. The registry record does not report covariate-adjusted analyses, model diagnostics, or a detailed account of the test used. The unadjusted result should therefore not be presented as a fully specified analysis plan.

Why do the standard deviations matter?

Standard deviations describe variability among observed scores, not uncertainty in the mean difference itself. When scores vary considerably within groups relative to the difference in group means, it is harder to estimate a precise contrast from a limited set of observations. The posted standard deviations, 2.3 and 2.4, are large in relation to the absolute mean difference of 0.2. This helps explain why the interval is broad, while not replacing the interval as the direct expression of uncertainty.

General statistical methods often rely on assumptions about the observations and the way participants enter the analysis. Randomization supports a comparison of assigned groups, but it does not by itself resolve missing outcome data, protocol deviations, or problems in measurement. The registry record does not provide participant-level data or details sufficient to assess these matters. The outcome population is specifically described as those with a charted pain score at the stated time, so the posted endpoint summary should be understood in that context.

How should the randomized comparison be framed?

The arms share scheduled ibuprofen, and differ in the additional tablet: acetaminophen in one arm and placebo in the other. The comparison therefore addresses the contrast between those assigned regimens, as recorded, rather than a contrast between ibuprofen and no ibuprofen. Assignment is randomized according to the registry record. However, the record does not report adherence, crossovers, or the analysis population used, so it is not possible to determine whether the posted summaries reflect assignment regardless of actual use or another approach.

The registry labels the trial triple-masked, while its brief summary calls it double-blinded. Masking can reduce the influence of expectations on treatment delivery, reporting, and outcome assessment, but these labels do not identify who was masked or how masking was maintained. The registry record does not resolve the difference between its descriptions. It is therefore appropriate to note the reported masking information without assuming further operational details.

The comparison's p-value and interval are not accompanied by a listed sponsor-reported analysis. The trial record does not report an analysis plan, a prespecified primary contrast procedure, or a missing-data method. The simple interpretation is consequently limited to the posted means, standard deviations, contrast, interval, and p-value. These describe the available registry results but cannot answer all questions about the conduct or planned analysis of the trial.

11. Confidence Intervals and Precision

The primary mean difference is -0.2, with an interval from -1.78 to 1.38. The point estimate is close to zero, but the interval is wide enough to include zero as well as differences on either side. Thus, the estimate is not precise enough to establish the direction of the underlying average difference. The interval's exact confidence level is not reported in the registry record, so it should not be assigned a specific confidence percentage.

Precision is distinct from whether a result crosses a chosen statistical threshold. The interval communicates the range of estimates compatible with the data and method; the p-value is another summary of the comparison under a null model. Neither tells whether a difference matters clinically. The registry record does not report a clinically important difference threshold for the pain scale, preventing a direct assessment of whether the interval rules out effects that would matter in practice.

The endpoint summaries include 17 participants in each arm, and the observed standard deviations are 2.3 and 2.4. With variability in participant scores and a limited number contributing to the endpoint, uncertainty in the mean difference is expected. The registry does not explain why the primary endpoint counts are smaller than the overall enrollment or report how missing scores were handled. Those omissions constrain assessment of both precision and potential bias.

The interval should not be read as proof that all values within it are equally plausible, nor as a guarantee that the true difference lies within it. It is a method-based uncertainty summary. The posted result supports a cautious description: the observed group means were close, but appreciable uncertainty remains about the size and direction of the difference.

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 estimates express the number of participants per arm, not a total across the trial. They are based on a planning illustration using the observed effect, rather than the trial's original design assumptions. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. For each planning scenario, the effect to detect is the stated fraction of the observed effect.

The 80% power column describes a hypothetical design that would have an 80% chance of detecting the specified effect under the stated assumptions, if that effect were the true one and the model assumptions held. The 90% power column uses a higher target chance of detecting that effect and consequently requires a larger planned sample. These are prospective planning quantities, not a measure of what this completed trial achieved. This is not observed power.

The rows illustrate planning for 100%, 75%, and 50% of the observed effect. Smaller effects are harder to distinguish from random variation, so planning for a smaller effect requires more participants per arm. The primary-outcome illustrations are particularly large because the observed contrast is small relative to the variability in scores. That does not show that the trial was designed with these targets; the original sample-size justification is not reported in the registry record.

The estimates are illustrations, not a retrospective judgment that a trial has or lacks sufficient power. They depend on the observed effect, which can be unstable in a small study, and on the stated assumptions. The registry record does not report any further design assumptions, such as allowance for missing outcomes or a different target effect. The estimates should therefore be read as conditional planning aids rather than as evidence about the trial's original design or its results.

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 = -0.200; pooled standard deviation σ = 2.351.
2. n = 2 × (1.96 + 0.842)² × 2.351² / -0.200² = 2,168.3, rounded up to 2,169 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 <- -0.2                      # observed difference in means
sigma <- 2.35053185470863                     # 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(3929640)
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 = 2,169 (80% power), 2,903 (90% power)
 75% of observed effect: n per arm = 3,855 (80% power), 5,161 (90% power)
 50% of observed effect: n per arm = 8,674 (80% power), 11,611 (90% power)
power.t.test: 2169.2 
Simulated power at n = 2,169 per arm: 0.798 (20000 replicates)

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

14. Multiplicity, Missing Data and Analysis Populations

The registry names several secondary outcomes in addition to the primary pain score. Examining multiple outcomes creates a multiplicity concern: even when there is no underlying difference, a collection of tests can produce a seemingly notable result by chance. General approaches include prespecifying a primary outcome, adjusting for the number or structure of comparisons, or treating secondary analyses as exploratory. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a detailed statistical analysis plan. The posted secondary p-values should therefore be interpreted as unadjusted rather than as confirmatory evidence across the outcome set.

The registry record lists five secondary outcomes, but numerical results are posted for only three of the WHOQOL-BREF domains. Results for in-hospital opiate consumption and Domain 4 are not reported in the registry record. It is not possible to infer whether these results were collected, analyzed, omitted, or unavailable for another reason. Their absence limits the ability to assess selective outcome reporting or the overall pattern across the planned secondary outcomes.

The primary outcome population is defined by having a charted post-operative day 2 mid-day pain score. The primary group summaries each include 17 participants, whereas enrollment is listed as 49. The registry record does not describe the flow of participants from enrollment to outcome assessment, explain missing scores, or state how missing data were handled. It also does not identify whether the analysis followed randomized assignment for all participants or used another analysis population. These details matter because missingness and exclusions can affect how representative the analyzed participants are of the randomized groups.

The trial is reported as randomized, but the record does not provide allocation concealment details, protocol deviations, adherence data, or a full analysis plan. These omissions do not establish that any particular bias occurred; they limit assessment of whether it could have influenced the results. The registry record also does not report interim analyses or the original sample-size justification. Without those details, the posted outcome summaries cannot be checked against the trial's intended analytic 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.

For serious adverse events, the registry reports zero affected participants in the ibuprofen-and-placebo group, with 20 at risk, and zero affected participants in the ibuprofen-and-acetaminophen group, with 21 at risk. For other adverse events, it likewise reports zero affected participants in each group, with 20 and 21 at risk, respectively. Deaths are reported as zero in both groups.

These figures describe the adverse-event counts entered in the registry for the stated groups. They do not establish that no adverse events of any kind occurred outside the reported categories, nor do they show that the regimens have identical safety profiles. A zero count in a limited study can coexist with uncertainty about uncommon events. The registry record does not provide event descriptions, severity details beyond the serious/other categories, exposure duration, or a fuller account of safety ascertainment. Safety interpretation should therefore remain limited to the posted counts and at-risk figures.

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

The primary result describes the observed average pain scores for the participants represented in the endpoint summaries. The mean was 3.5 with ibuprofen and placebo and 3.3 with ibuprofen and acetaminophen. The estimated mean difference was -0.2, with an interval from -1.78 to 1.38. The interval includes no difference and estimates in both directions, so the result does not precisely determine the direction or size of a difference in the underlying population.

This does not demonstrate that the regimens are equivalent. Equivalence is a specific research claim that depends on a prespecified acceptable range and an analysis designed to test whether the difference lies within that range. The registry record does not report such a range or an equivalence analysis. Nor does the posted result establish that either regimen does or does not improve pain. It reports a comparison between two assigned schedules that both included ibuprofen.

The result also cannot establish that a particular difference would be meaningful to patients. No clinically important threshold for the pain scale is reported in the registry record. The group means summarize averages and do not convey every participant's response or the distribution of scores. The registry record does not provide individual-level results that would allow a more detailed view of variation in response.

The secondary quality-of-life estimates are limited by uncertainty, unadjusted comparisons, and incomplete numerical reporting across the listed outcomes. They should not be used to make stronger claims than the primary result supports. Similarly, the adverse-event figures report no affected participants in the listed categories, but do not rule out uncommon events or establish a complete safety comparison.

The trial's terminated status and enrollment information are part of the record, but the reason for termination and its implications are not reported. The findings should therefore be understood as registry-posted summaries with important gaps in analysis and outcome-flow details. They do not replace a complete account of trial conduct, nor do they provide medical advice or a basis for choosing a regimen.

17. Why This Trial Matters Statistically

This trial illustrates a central challenge in clinical research: a small observed difference does not necessarily translate into a precise estimate. The two primary group means are close, but the interval around their difference is broad enough to include effects in either direction. Reporting the estimate together with its uncertainty avoids turning a single point estimate or p-value into an overconfident conclusion.

The comparison is also a useful example of defining the treatment contrast carefully. Both arms received scheduled ibuprofen; the randomized difference was the accompanying acetaminophen or placebo. Clear framing prevents the result from being misread as a comparison of ibuprofen against no ibuprofen. The registry's masking descriptions also demonstrate why operational details matter: the masking field and brief summary use different labels, and the record does not resolve the distinction.

Finally, the record highlights the importance of linking enrollment, endpoint populations, missing data, and analysis plans. The enrollment figure is not the same as the count contributing to the primary endpoint, and the reason is not reported. Several secondary outcomes are listed without numerical results, while posted secondary comparisons are unadjusted. These details affect the strength and completeness of interpretation, even when the numerical summaries themselves are straightforward.

18. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations specific to this record constrain interpretation. The trial is marked terminated, but the reason is not reported. The registry gives an enrollment of 49, while the primary outcome summaries include 17 participants per arm; participant flow and the reasons for the different counts are not described. The endpoint population is limited to those with a charted post-operative day 2 mid-day pain score, and missing-data handling is not reported.

The registry does not provide the original sample-size justification or a detailed statistical analysis plan. It does not report an analysis population, adjusted analyses, or whether the posted primary comparison follows a prespecified procedure. The primary outcome interval's confidence level and construction are also not specified. These gaps make it harder to evaluate how closely the posted summaries reflect the intended analysis.

Only numerical results for three of the listed secondary outcomes are posted. The record does not report numerical results for in-hospital opiate consumption or WHOQOL-BREF Domain 4, and does not explain their absence. Multiplicity handling is not reported, so the secondary comparisons should be viewed cautiously. The trial's masking field says triple, while its brief summary says double blinded; details that would clarify masking are absent.

The record does not report adherence, medication exposure, participant-level outcome distributions, or a clinically important difference threshold for pain. These omissions limit assessment of treatment delivery, score variability, and clinical relevance. The adverse-event summaries are counts for the listed categories and do not provide detailed event descriptions or broader safety context. These are limitations of the available registry record, not evidence that a particular problem occurred.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Management Of Pain After Cesarean Trial — NCT03929640.
• Registry record last updated 2024-09-04; status last verified 2024-08.
• Results first posted 2024-09-04.
• 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

NCT03929640 is a randomized, parallel-group Phase 3 trial sponsored by Milton S. Hershey Medical Center and listed as terminated. It compared scheduled ibuprofen 600 mg plus acetaminophen 650 mg with scheduled ibuprofen 600 mg plus placebo after cesarean delivery. The primary outcome was participant-reported pain on post-operative day 2, measured mid-day on a scale from 0 to 10.

The posted primary means were 3.3 in the combination group and 3.5 in the placebo group. The unadjusted mean difference was -0.2, with an interval from -1.78 to 1.38 and p = 0.804. The interval includes zero and values in either direction, indicating uncertainty about the size and direction of the difference. The record also posts results for three quality-of-life domains, but not for all listed secondary outcomes. Reasons for termination, the original sample-size rationale, missing-data handling, and a full statistical analysis plan are not reported in the registry record.