Prostaglandin E1 in Outpatients With Intermittent Claudication: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Prostaglandin E1 in Outpatients With Intermittent Claudication (NCT01263925), a randomized phase 3 study. The primary outcome is Ratio of Pain-free Walking Distance After Period 2 in Comparison With the Findings at Baseline.

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, double-masked, parallel-group trial of intravenous prostaglandin E1 treatment in outpatients with intermittent claudication. The registry lists an enrollment of 561 and a completed trial. The record gives 2001-04 as the start and 2011-04 as the primary completion date. It names UCB Pharma as the sponsor.

The two treatment regimens paired active medication by one route with matching placebo by the other route: alprostadil intravenously with oral placebo, or pentoxifylline orally with intravenous placebo. The study summary describes an investigation of daily treatment for 4 weeks and interval treatment for 4 weeks, with two infusions per week in the interval regimen. The primary outcome timeframe is from baseline to the end of interval treatment, identified as Period 2. The registry also identifies follow-up through Period 3 at 6 months.

For the primary outcome, the arm summaries include 269 participants in the alprostadil group and 272 in the pentoxifylline group. These are the numbers attached to the posted outcome summaries; they should not be read as a full account of participant flow. The record does not give a flow diagram or explain how these outcome counts relate to enrollment.

The registry names a Full Analysis Set for the primary outcome, but its inclusion rules are not reported in the registry record. The original sample-size rationale, allocation procedure, masking procedures, treatment adherence, withdrawals, and protocol deviations are also not reported in the registry record. The randomized design supports a comparison of the assigned regimens, while the available registry summaries do not resolve how these design and analysis details were handled.

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: Participant Flow shows all randomized subjects. Baseline Characteristics refer to the FAS.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS).

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 Ratio of Pain-free Walking Distance After Period 2 in Comparison With the Findings at Baseline, measured over From Baseline to the end of 4 weeks of Interval Treatment (Period 2).

The primary endpoint is a ratio: pain-free walking distance at the end of Period 2 divided by pain-free walking distance at baseline. It is expressed in meter/meter, and the registry reports a mean and standard deviation for each treatment group. A ratio places the follow-up measurement in relation to the participant’s baseline measurement, rather than reporting only the follow-up distance. A mean above 1 represents an average ratio above baseline; the group mean should not be mistaken for the experience of every participant.

The outcome was measured on a treadmill at a 12 % grade and 3 km/h. The registry says that participants unfamiliar with the treadmill had at least two test determinations to become accustomed to it, and that participants could not see the displayed walking distance during treadmill determinations. These procedures address familiarity and visibility of the distance display, but the record does not give additional measurement-reliability results.

Pain-free walking distance is relevant to intermittent claudication because the outcome records walking up to the onset of pain. The ratio format permits comparison with baseline, while the treatment-group contrast asks whether the average ratios differed between regimens. The endpoint alone does not describe all aspects of walking ability, symptoms, daily functioning, or safety.

7. Results Posted in the Registry

• Pentoxifylline: mean 1.98 versus 2.60 on control; difference -0.62 (95% CI -2.14 to 0.90), standardized effect d = -0.07; z-test p = 0.425.

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.

Ratio of Pain-free Walking Distance After Period 2 in Comparison With the Findings After Period 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:
  • Pentoxifylline: mean 1.24 versus 1.25 on control; difference -0.01 (95% CI -0.11 to 0.09), standardized effect d = -0.02; z-test p = 0.840.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Pentoxifylline and the control. The interval gives the range of effects that remain compatible with the data.

Ratio of Pain-free Walking Distance After Period 3 in Comparison With the Findings After Period 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:
  • Pentoxifylline: mean 1.57 versus 1.54 on control; difference 0.03 (95% CI -0.19 to 0.25), standardized effect d = 0.02; z-test p = 0.794.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Pentoxifylline and the control. The interval gives the range of effects that remain compatible with the data.

Ratio of Pain-free Walking Distance After Period 3 in Comparison With the Findings After Period 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:
  • Pentoxifylline: mean 1.28 versus 1.26 on control; difference 0.02 (95% CI -0.11 to 0.15), standardized effect d = 0.03; z-test p = 0.770.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Pentoxifylline and the control. The interval gives the range of effects that remain compatible with the data.

The registry identifies secondary outcomes involving pain-free and maximum walking distances across treatment periods and follow-up. The posted comparative summaries for pain-free walking-distance ratios across Period 1, Period 2, and Period 3 have estimates close to zero, and their displayed intervals include zero. Their point estimates do not show a consistent direction of separation between the treatment groups across the reported comparisons. These summaries broadly echo the primary result in the sense that they do not provide a clear separation, but they are not proof that the regimens have equivalent outcomes.

These secondary comparisons concern changes in the timing of measurement: interval treatment relative to daily treatment, follow-up relative to earlier periods, and follow-up relative to interval treatment. They therefore address different questions from the primary baseline-to-Period-2 ratio. Their results should not be collapsed into one conclusion about every aspect of walking distance or the course of outcomes.

Secondary findings generally carry less weight when many outcomes or comparisons are examined. The more comparisons considered, the greater the chance that some result may appear notable by chance. Whether the trial used a prespecified order of testing, a multiplicity adjustment, or another strategy is not reported in the registry record. The available secondary p-values are unadjusted, so they should be read as exploratory rather than as stand-alone confirmatory evidence.

The registry metadata counts 11 secondary outcomes as posted, while the record does not provide a reported analysis for every listed outcome. The pattern in the available summaries should therefore be interpreted with attention to which comparisons have numerical results and which are not represented by a posted comparison. Missing secondary analyses cannot be taken to imply either a favorable or unfavorable result.

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

• Ratio of Pain-free Walking Distance After Period 2 in Comparison With the Findings After Period 1
• Ratio of Pain-free Walking Distance After Period 3 in Comparison With the Findings After Period 1
• Ratio of Pain-free Walking Distance After Period 3 in Comparison With the Findings After Period 2
• Ratio of Maximum Walking Distance After Period 1 in Comparison With the Findings at Baseline
• Ratio of Maximum Walking Distance After Period 2 in Comparison With the Findings at Baseline
• Ratio of Maximum Walking Distance After Period 2 in Comparison With the Findings After Period 1
• Ratio of Maximum Walking Distance After Period 3 in Comparison With the Findings at Baseline
• Ratio of Maximum Walking Distance After Period 3 in Comparison With the Findings After Period 1

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous and summarized by a mean and standard deviation. A mean gives the arithmetic average of the measured ratios within an arm. A standard deviation describes how dispersed individual values are around that average; it is not the uncertainty of the mean itself. The endpoint’s ratio scale is dimensionless in the sense that the same distance unit appears in numerator and denominator, although the registry records the unit as meter/meter.

What does the group contrast represent?

The contrast is the pentoxifylline mean minus the alprostadil mean. The estimate of -0.62 describes the direction and size of the difference between those posted group means on the ratio scale. The estimate does not say that every participant in one group had a lower value, and it does not represent a within-person change by itself. Although each participant’s outcome uses a baseline measurement, the listed contrast compares group averages.

The arm summaries report the alprostadil mean as 2.6 with standard deviation 12.22 and the pentoxifylline mean as 1.98 with standard deviation 3.61. The comparison also gives a pooled standard deviation of 8.989 and a standardized difference of -0.069. A standardized difference expresses a contrast relative to a measure of variation; it can help describe scale-free magnitude, but it does not establish clinical importance. The registry does not report a clinical threshold for interpreting either measure.

How should the interval and p-value be read?

The comparison interval runs from -2.142 to 0.902. In general, an interval estimate describes a range of values compatible with the data and the method used, subject to the method’s assumptions. Here, the displayed interval includes zero, the value corresponding to no mean difference. Its breadth signals uncertainty in the estimated contrast. The confidence level and construction method for this interval are not reported in the registry record, so they should not be inferred from the limits alone.

The unadjusted p-value is 0.425. In general, a p-value measures how unusual data at least as incompatible with a specified null model would be if that model were true, under the assumptions of the test. It does not give the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. The registry record does not report the test used for a sponsor analysis; the posted p-value is associated with the unadjusted comparison.

Why does variability matter?

When outcome values vary widely, a group mean may be estimated less precisely than it would be with less variability, all else equal. The especially large alprostadil standard deviation relative to its mean signals that the mean alone may not capture the range of participant outcomes. This does not identify why the observations vary, whether the distribution is skewed, or whether particular observations are influential. Those questions require information not reported in the registry record.

Over-dispersion is a general concern when observed variability exceeds what a chosen statistical model expects. A model that understates variability can yield intervals that are too narrow and tests that appear more decisive than warranted. The registry does not report a model-based variance assumption or a diagnostic assessment, so over-dispersion cannot be diagnosed from the summary data alone. The differing standard deviations do, however, make it important not to treat the group means as a complete account of the data.

What is and is not recalculated?

The contrast and its associated interval and p-value are unadjusted recalculations from posted summary statistics. They do not represent a covariate-adjusted result, a repeated-measures model, or a participant-level analysis. The record does not provide the covariance structure between baseline and follow-up measurements, which could matter for analyses of change or repeated measurements. No sponsor analysis is listed in the registry record, and no discrepancy between the recalculation and a sponsor result is identified.

These methods describe the available numerical summaries, not the full analytic conduct of the trial. The original statistical analysis plan, handling of missing measurements, assumptions behind the primary test, and adjustments for secondary comparisons are not reported in the registry record. Those omissions limit how much can be concluded about the prespecified inferential framework.

11. Confidence Intervals and Precision

The primary comparison estimate is -0.62, with an interval from -2.142 to 0.902. The interval includes zero and extends into negative and positive values. Thus the point estimate alone should not be treated as a precise estimate of the direction or magnitude of a population difference. The interval is compatible with a range of contrasts, rather than identifying a narrow effect.

In general, a confidence interval combines an estimate with uncertainty under a stated statistical method. Its interpretation depends on the method and confidence level, neither of which is stated for this comparison in the registry record. The displayed limits can still be read as indicating substantial uncertainty around the unadjusted mean difference, but a confidence level should not be assigned without documentation.

The arm-level summaries show standard deviations of 12.22 for alprostadil and 3.61 for pentoxifylline. These values describe variability among outcome observations, not precision of the group means. The difference in dispersion, particularly the large alprostadil standard deviation, is relevant context for the uncertain contrast. Without individual-level values, the distribution and potential influence of extreme observations cannot be evaluated.

The interval does not demonstrate equivalence or prove that the regimens have the same average outcome. Equivalence requires a prespecified margin and an appropriate analysis; neither is reported in the registry record. Nor does an interval spanning zero show that all clinically relevant effects have been excluded. The record provides no clinical-importance threshold against which to judge the limits.

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 for this continuous outcome are participants per arm, not a total across arms or a count of events. They are planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each row considers detecting 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 80% power column describes the number of participants per arm that the stated planning calculation would require to give an 80% chance of detecting the assumed effect under its model and significance level, if that assumed effect were the true effect. The 90% power column uses the same interpretation with a higher target chance of detection. These are prospective planning quantities, not a guarantee that a study will produce a particular result.

The rows for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect illustrate that smaller assumed effects require more participants per arm to detect, all else equal. The figures become large because the observed standardized difference is small. They should not be interpreted as a recommendation for a future study without a separate design assessment, including a clinically meaningful target effect and appropriate assumptions.

This is not observed power. Observed power would use the effect estimate from the completed study and is not a useful replacement for interpreting the estimate and its uncertainty. The planning calculations instead show how sample-size requirements change under their stated assumptions.

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 = -0.620; pooled standard deviation σ = 8.989.
2. n = 2 × (1.96 + 0.842)² × 8.989² / -0.620² = 3,299.7, rounded up to 3,300 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 <- -0.62                      # observed difference in means
sigma <- 8.98893468400159                     # 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(1263925)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 3,300 (80% power), 4,418 (90% power)
 75% of observed effect: n per arm = 5,867 (80% power), 7,854 (90% power)
 50% of observed effect: n per arm = 13,199 (80% power), 17,670 (90% power)
power.t.test: 3300.6 
Simulated power at n = 3,300 per arm: 0.797 (20000 replicates)

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

14. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and multiple secondary outcomes, including pain-free and maximum walking-distance ratios at different periods. Testing several outcomes or time comparisons creates a multiplicity issue: when many hypotheses are tested, the chance of at least one apparently unusual result can increase. This is a general statistical concern, not evidence that any particular reported result is false.

The registry record reports no analyses in its analysis count and lists no reported analyses. The displayed comparisons are unadjusted recalculations from outcome summaries. Whether the investigators prespecified a hierarchy, controlled a family-wise error rate, used a false-discovery approach, or applied another multiplicity strategy is not reported in the registry record. The unadjusted secondary results should consequently be given less weight than a result from a documented confirmatory testing plan.

The primary outcome population is named as the Full Analysis Set. The registry does not define its membership, describe exclusions, or provide enough information to determine how closely it follows an intention-to-treat principle. The outcome-specific group counts are reported, but participant flow, missing measurement counts, reasons for missingness, and the method used to address missing data are not reported in the registry record.

Missing data can affect estimates if the availability of a measurement is related to outcome or treatment. Complete-case summaries, imputation, and model-based approaches make different assumptions; the record does not identify which approach was used for the posted means. It also does not report sensitivity analyses for missing outcomes. These gaps prevent assessment of how robust the primary and secondary comparisons are to incomplete follow-up.

The registry does not report the original statistical analysis plan, details of interim analyses, or the trial’s sample-size justification. It is therefore not possible to verify from the registry record whether the displayed outcome analyses correspond to the original prespecified plan.

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 0.5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: peripheral arterial occlusive disease (1.4%), coronary artery disease (1.1%), carotid artery stenosis (1.1%), angina pectoris (0.7%), left ventricular failure (0.7%).

For serious adverse events, the registry reports 19 affected among 276 at risk in the alprostadil group and 17 among 285 at risk in the pentoxifylline group. For other adverse events, it reports 60 among 276 at risk and 55 among 285 at risk, respectively. These are group counts and denominators as recorded; they are not comparative risk estimates, and no new rates are calculated.

The registry lists serious-event terms with percentages, including Peripheral Arterial Occlusive Disease at 1.4%, Coronary Artery Disease at 1.1%, Carotid Artery Stenosis at 1.1%, Angina Pectoris at 0.7%, Left Ventricular Failure at 0.7%, and Iron Deficiency Anaemia at 0.4%. The record does not specify these terms by treatment group in the listed summary, so they should not be used to compare groups.

Deaths are not reported in the registry record. The available adverse-event summaries do not establish whether an event was caused by treatment, and the registry does not give event timing, duration, severity grading beyond the serious classification, or details of how events were collected. The counts describe recorded safety outcomes but do not by themselves settle comparative safety.

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

The posted primary result describes average ratios of pain-free walking distance after interval treatment relative to baseline. The alprostadil group mean was 2.6 and the pentoxifylline group mean was 1.98. The unadjusted mean difference was -0.62 for pentoxifylline relative to alprostadil, with an interval that includes zero. This is evidence about the available group summaries, not a definitive answer about every participant’s response or every clinically relevant outcome.

The result does not establish that the treatments are equivalent. A non-significant unadjusted p-value and an interval containing zero do not prove equality; an equivalence or non-inferiority question requires a prespecified margin and a design and analysis tailored to that purpose. Such a margin is not reported in the registry record. The result also does not establish that either regimen is better or worse in practical terms, because clinical importance is not defined by a threshold in the registry.

The primary endpoint is a treadmill-based measure of pain-free walking distance. It should not be interpreted as a direct measure of all daily walking, quality of life, or long-term function. The record describes follow-up through Period 3 and additional walking-distance outcomes, but the available summaries do not replace a full account of participant-level outcomes over time.

Interpretation is limited by variability in the primary outcome, uncertainty around the comparison, and the absence of details on missing data, analysis methods, and multiplicity. The registry also does not provide the original sample-size rationale or a complete report of trial conduct. These limitations mean that the posted numerical result should be read as a cautious summary, not as a treatment recommendation or a comprehensive assessment of benefits and harms.

17. Why This Trial Matters Statistically

This trial illustrates how a randomized, double-masked design can frame a comparison of treatment regimens while still leaving important statistical questions unanswered in a registry record. The outcome is a ratio of follow-up to baseline walking distance, but the between-group estimate is a difference between mean ratios. Keeping the scale and contrast clear helps avoid interpreting the result as a raw distance difference or as an individual-level treatment effect.

The primary point estimate is accompanied by a broad interval that includes zero, and the group standard deviations differ substantially. This makes the distinction between the observed estimate and the precision of that estimate central to interpretation. A single p-value cannot communicate the range of effects compatible with the data, the outcome variability, or the clinical relevance of possible differences.

The record also provides a useful example of why planning calculations should be separated from claims about a completed trial. The sample-size illustrations use an observed effect and explicit planning assumptions; they do not show the trial’s original design rationale, and they are not observed power. Likewise, an unadjusted secondary comparison does not carry the same evidential weight as a prespecified primary analysis with a documented multiplicity plan.

Finally, registry summaries can make group counts and outcome summaries accessible without documenting all analysis choices. Clear boundaries between posted descriptive data, recalculated contrasts, and unreported design or analysis details are essential for responsible interpretation.

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 primary outcome is based on treadmill testing, and the registry describes familiarization for participants unfamiliar with the treadmill and concealment of the distance display. It does not report the reliability of the measurements, the distribution of treadmill performance, or whether measurement conditions were consistent across visits. The endpoint captures pain-free walking under the stated treadmill conditions, which may not represent walking in all settings.

The primary outcome’s alprostadil standard deviation is 12.22, compared with a mean of 2.6, while the pentoxifylline standard deviation is 3.61 and its mean is 1.98. These summaries indicate substantial variability, but the record does not provide participant-level data to examine skew, influential values, or heterogeneity of response. The reported group means therefore give an incomplete picture of the outcome distributions.

The registry identifies the Full Analysis Set but does not define it. It does not report the number or reasons for missing endpoint measurements, treatment adherence, withdrawals, protocol deviations, or the method used to handle missing data. The outcome analysis counts should not be assumed to describe all enrolled participants or all randomized participants.

The registry does not report the original sample-size justification, the confidence level or construction method for the comparison interval, a detailed statistical analysis plan, or any multiplicity adjustment. No sponsor analysis is listed. Thus the unadjusted recalculation cannot be checked against a documented primary inferential method. The available safety summaries also omit deaths and details of event timing, attribution, and collection. These are limitations of what the registry record reports, not proof that the trial did not collect such information.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Prostaglandin E1 in Outpatients With Intermittent Claudication — NCT01263925.
• Registry record last updated 2014-10-27; status last verified 2012-05.
• Results first posted 2012-06-29.
• 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

NCT01263925 is a completed Phase 3, randomized, double-masked, parallel-group trial sponsored by UCB Pharma. It enrolled 561 participants with Stage II peripheral arterial occlusive disease or intermittent claudication and compared intravenous alprostadil with oral pentoxifylline, using matching placebos by the alternate route.

The primary outcome was the mean ratio of pain-free walking distance after 4 weeks of interval treatment to baseline. The posted group means were 2.6 for alprostadil and 1.98 for pentoxifylline; the unadjusted recalculated mean difference was -0.62, with an interval from -2.142 to 0.902 and p = 0.425. The interval includes zero, and the registry does not report a sponsor analysis or the original statistical analysis plan.

The registry includes additional walking-distance outcomes and adverse-event summaries. Missing-data methods, multiplicity procedures, detailed participant flow, and the trial’s original sample-size justification are not reported in the registry record.