Prospective Randomized Endovascular Therapy in Multiple Sclerosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Prospective Randomized Endovascular Therapy in Multiple Sclerosis (NCT05380362), a randomized na study. The primary outcome is Percentage of Patients With Immediate and Short-term SAE.

2. Clinical Question

The trial asks whether venous angioplasty for venous stenoses in people with multiple sclerosis and CCSVI can be evaluated for short-term safety and preliminary clinical effects against an angiography procedure without angioplasty. CCSVI is the condition named in the registry record; the record describes its assessment using Doppler ultrasound. The study also aimed to examine venous anatomy and changes in clinical, imaging, quality-of-life, fatigue, and functional measures.

These aims should be kept distinct. The primary outcome is a safety measure, whereas relapse rate, disability progression, imaging, and self-reported outcomes appear among the study's broader aims. Their inclusion as aims does not establish that results for them were posted or that they were part of the primary outcome analysis.

3. Trial Design

The registry record describes a randomized, triple-masked, parallel-group trial. Its listed phase is NA, and its status is completed. The listed enrollment is 30. The sponsor is the University at Buffalo. The recorded start is 2010-06, and primary completion is listed as 2013-04.

The intervention arms are venous angioplasty and angiography without angioplasty. The arm descriptions use slightly different wording: one says 20 patients will have venous angioplasty, while the other describes an angiogram with no angioplasty and says the patient will not be aware of the assigned treatment. The posted primary outcome results list 9 participants in the venous angioplasty arm and 10 in the angiography-without-angioplasty arm. These figures do not explain the difference between the listed enrollment and the outcome groups; the participant flow and reasons for the reported group sizes are not reported in the registry record.

Random allocation and masking are features of the recorded design, not proof that every aspect of implementation or follow-up was complete. The registry identifies triple masking but does not specify which roles were masked or how masking was maintained. Details about allocation concealment and the randomization procedure are not reported in the registry record.

The study description lists a broad set of objectives: safety, venous morphology, preliminary clinical and imaging efficacy, quality of life, fatigue, functional measures, attention, and associated brain changes on functional MRI. However, the posted outcome record contains one outcome measure, the serious adverse event measure. Results for the broader objectives are not reported in the registry record. Accordingly, the design description provides context for the study, but the available outcome result answers only a narrow safety question.

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

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 Percentage of Patients With Immediate and Short-term SAE, measured over 1 month post-procedure.

The primary endpoint is titled Percentage of Patients With Immediate and Short-term SAE. SAE refers to severe adverse events in the outcome description. The endpoint is a binary participant-level outcome: whether a participant had a serious adverse event during the specified safety assessment. The record lists the timeframe as 1 month post-procedure and describes the outcome as a percentage, although the posted arm values are counts of participants with an event.

This kind of outcome is used to describe procedural safety. A clear event definition and a specified observation period help establish what is being counted and when it is counted. The registry says that immediate and short-term serious adverse event rates were to be accompanied by 95% confidence intervals using the exact method, and that Fisher's exact test was to be used for comparisons. These statements describe the intended statistical approach; the corresponding confidence intervals and test results are not reported in the registry record.

A zero event count is informative about what was observed in the posted groups, but it does not establish that the underlying risk is zero. With limited observations, uncertainty around an event rate can remain substantial even when no events are recorded. The record does not provide the event definition, adjudication process, or additional detail on how the immediate and short-term assessment periods relate to the listed 1 month timeframe. Those omissions limit interpretation of the endpoint beyond its stated purpose as a short-term safety measure.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary safety outcome is binary at the participant level: a participant either had a serious adverse event during the assessment period or did not. The posted values are event counts, and the record also gives the number at risk in each arm. For a binary endpoint, an event rate is ordinarily expressed as the number of participants with the event relative to the number assessed. The registry outcome is titled as a percentage, but the posted values are counts rather than percentages. No separate percentage estimates are reported in the registry record.

Why use a confidence interval?

General statistical explanation: an observed rate is an estimate of an underlying event probability, not a guarantee of the exact risk in a wider population. A confidence interval describes uncertainty around that estimate under the assumptions of the method. When few events are observed, and especially when the observed count is zero, the data can still be compatible with a range of underlying risks. An interval is therefore important for interpreting a zero count; the count alone does not convey its precision.

The registry specifies the exact method for the 95% confidence intervals for immediate and short-term serious adverse event rates. Exact methods are useful for sparse binary data because they do not rely on the same large-sample approximation used by some simpler interval methods. The confidence intervals themselves are not posted, so the precision of the arm-specific rates cannot be read directly from the registry result. The record also does not explain whether the listed 1 month timeframe represents the short-term assessment alone or how it relates to the immediate assessment named in the outcome description.

What does Fisher's exact test assess?

General statistical explanation: Fisher's exact test evaluates whether the observed distribution of a binary outcome across two groups is compatible with a null hypothesis of no association between group and outcome, under the test's assumptions. It is often considered for small samples or sparse event counts. A test result does not measure the size or clinical importance of a difference, and a non-significant result would not establish equivalence. Interpretation requires an effect estimate and its uncertainty as well as the test result.

The registry states that Fisher's exact test was to be used for the immediate and short-term comparisons. However, no comparative test result or confidence interval is reported. The posted counts can be described, but a claim about a statistically significant difference, or the absence of one, cannot be supported from a test result that is not reported in the registry record.

Why can sparse data be difficult to interpret?

General statistical explanation: when event counts are sparse, estimates may be imprecise and conventional approximations may perform poorly. This is one reason exact procedures may be selected. Sparse data also make it difficult to distinguish a genuinely low event probability from a low observed count arising by chance. A zero count should therefore be interpreted as no event observed in the recorded group, rather than as proof of no possible risk.

Over-dispersion is a general concern when event variability exceeds what a simple model expects. It can make model-based standard errors too small if it is ignored. The posted primary endpoint is a binary participant outcome, and the record specifies exact confidence intervals and Fisher's exact test rather than describing an over-dispersion model. No additional modeling approach is reported in the registry record.

What do planning calculations mean?

General statistical explanation: a sample-size calculation uses assumptions about the effect to be detected, the significance level, allocation, and statistical method to illustrate the amount of information a future study might need. The planning assumptions recorded for this trial describe a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Those are planning assumptions, not evidence that the trial had a particular probability of detecting an effect.

Any planning illustration based on an observed effect is distinct from observed power. Observed power is not a substitute for interpreting the estimate and its uncertainty after data have been collected. The registry record does not report the trial's own sample-size justification, and the listed planning assumptions should not be treated as proof of the design rationale. No planning value should be read as an observed trial outcome.

What can be concluded from the posted analysis?

The registry posts arm-specific counts for the primary safety outcome but no analysis results. The record lists zero posted analyses. No adjusted or unadjusted comparative effect estimate, confidence interval, or p-value is reported in the registry record. Consequently, statistical interpretation is limited to describing the observed counts and identifying the methods named in the outcome description. The results do not support reconstructing an unreported analysis or substituting a new calculation for the sponsor's analysis.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Venous Angioplasty", "Angio With no Plasty")
n      <- c(9, 10)
events <- c(0, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Venous Angioplasty  9  0  0.0  0.0  33.6  -0.0  29.9  0.3  30.8
ARM  Angio With no Plasty  10  0  0.0  0.0  30.8  0.0  27.8  0.2  28.5

11. Multiplicity, Missing Data and Analysis Populations

The study description contains several objectives beyond the primary serious adverse event outcome, including clinical, ultrasound, MRI/MRV, quality-of-life, fatigue, functional, attention, and functional MRI measures. The registry outcome record posts one outcome measure and lists no secondary outcomes. Results for the broader objectives are not reported in the registry record.

When a study tests multiple outcomes or multiple comparisons, the chance of at least one apparently positive finding can increase. General statistical approaches may address this through a prespecified hierarchy or adjustment, but the choice depends on the study's aims and analysis plan. The registry record does not report a multiplicity strategy, a testing hierarchy, or whether any adjustment was planned. Because comparative analyses are not posted, there is no basis for assessing how multiplicity was handled in results.

Missing-data methods and analysis populations are also not reported in the registry record. The record does not state whether the primary outcome analysis was intention-to-treat, per-protocol, or based on another population, and it does not describe imputation, exclusions, or participant-level missingness. The listed enrollment is 30, while the outcome groups report 9 and 10 participants at risk. The record does not explain this difference, so it cannot establish how participants not represented in those outcome groups were handled.

These gaps matter because outcome availability, analysis population, and multiplicity can affect interpretation even when the event counts themselves are clear. They should be treated as unreported information, not as evidence that a particular method was or was not used.

12. 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% reporting threshold.

Most frequent non-serious adverse event terms

The primary safety outcome reports zero serious adverse events among 9 participants at risk in the venous angioplasty group and zero among 10 participants at risk in the angiography-without-angioplasty group. The endpoint timeframe is listed as 1 month post-procedure. The result means that no serious adverse events were recorded in the posted groups for this outcome; it does not establish a zero underlying risk.

The adverse event listing also records three other adverse events in each group. The types of these events are not reported in the registry record, so their clinical importance, severity, timing, and relationship to treatment cannot be evaluated from the posted information. Equal counts do not imply that the events were identical or equally consequential.

The record says exact 95% confidence intervals and Fisher's exact tests were to be used for immediate and short-term serious adverse event rates. Those numerical results are not reported in the registry record. Without confidence intervals, the precision of the observed rates is not shown; without comparative test results, the record does not establish a statistical difference or equivalence between the groups.

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

The result supports a narrow descriptive statement: the registry reports no serious adverse events in the two posted outcome groups during the specified short-term assessment. The event counts and numbers at risk make clear what was observed in those groups. They do not determine the probability of an event in other participants, settings, or follow-up periods.

A zero count is not the same as proof of no risk. The relatively limited group sizes reported for the endpoint mean that the observed counts alone cannot provide a highly precise estimate of an uncommon event rate. The registry states that confidence intervals were intended, but does not report them. The planned comparison test is also not reported as a result. For that reason, the posted data do not establish whether the groups differ statistically or whether their safety is equivalent.

The study was designed to address more than safety. Its description names clinical outcomes, venous imaging, quality of life, fatigue, functional measures, attention, and brain changes. Yet the registry posts no results for those aims. The safety outcome cannot be used as a proxy for relapse, disability progression, quality of life, or imaging changes, and it does not answer whether angioplasty altered those outcomes.

The registry lists enrollment of 30 but reports outcome groups of 9 and 10 participants at risk. Without an explanation of participant flow or outcome availability, readers cannot determine why those figures differ or how the unrepresented participants were handled. The endpoint result is therefore best read as a limited report of observed serious adverse event counts, with important uncertainty about precision, analysis populations, and the broader trial findings.

It is appropriate to distinguish the observed result from a conclusion about treatment. The record documents counts and a planned statistical approach; it does not post the comparative estimates needed for a fuller assessment. No medical recommendation follows from these figures alone.

14. Why This Trial Matters Statistically

This trial is statistically notable because its primary endpoint concerns a safety outcome that can be uncommon and is recorded as a binary participant event. In that setting, an absence of observed events can look definitive while still leaving uncertainty about the underlying event rate. Reporting confidence intervals alongside counts is important for showing that uncertainty. The registry names an exact interval method, but does not post the intervals.

The design also illustrates why a randomized comparison and a descriptive result are not interchangeable. Randomization is recorded, but the posted data consist of event counts without the planned comparative test result or a comparative effect estimate. The counts describe the groups; they do not by themselves establish equivalence or a treatment-related difference.

Another important issue is alignment between study aims and posted outcomes. The trial description names a wide range of clinical and imaging questions, while the outcome record contains only the serious adverse event measure. Statistical interpretation must follow the outcomes actually reported rather than treating the listed aims as completed analyses. This distinction is central when registry information is used to understand the available evidence.

Finally, the listed enrollment and the reported outcome group sizes are not reconciled in the record. Transparent participant flow and analysis-population descriptions would help readers understand who contributed to the outcome and how missing observations were handled. These reporting details are not peripheral: they shape the denominator, the precision of estimates, and the scope of conclusions that can be drawn.

15. 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 registry result is limited to a single posted primary safety measure. Although the study description names efficacy, imaging, and patient-reported objectives, results for those outcomes are not reported in the registry record. The available figures therefore do not provide a broad assessment of the trial's stated aims.

The primary outcome description refers to immediate and short-term serious adverse event rates, while the listed timeframe is 1 month post-procedure. The relationship between these timing descriptions is not explained. The registry also does not provide a detailed operational definition of a serious adverse event, describe event adjudication, or identify the specific other adverse events recorded.

Although the record names an exact confidence-interval method and Fisher's exact test, it does not post the resulting intervals or comparative test. Without them, precision and comparative uncertainty cannot be assessed from the registry results. No effect estimate or analysis details are reported.

The listed enrollment is 30, whereas the primary outcome groups report 9 and 10 participants at risk. Participant flow, reasons for this difference, missing-data handling, and the analysis population are not reported in the registry record. The arm description that says 20 patients will have angioplasty also does not reconcile these figures. These inconsistencies limit assessment of how the reported groups relate to the trial as a whole.

Finally, the record does not report the randomization procedure, allocation concealment, masking roles, multiplicity strategy, or the trial's own sample-size justification. These absences do not establish that procedures were inadequate; they mean that the details cannot be evaluated from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Prospective Randomized Endovascular Therapy in Multiple Sclerosis — NCT05380362.
• Registry record last updated 2025-08-22; status last verified 2025-08.
• Results first posted 2025-08-22.
• 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.

19. Record Summary

The registry describes a completed randomized, triple-masked, parallel-group study of venous angioplasty versus angiography without angioplasty in people with multiple sclerosis and CCSVI. Enrollment is listed as 30, with the study beginning in 2010-06 and primary completion in 2013-04.

The posted primary outcome is the serious adverse event measure at 1 month post-procedure. It reports zero serious adverse events in the venous angioplasty group, with 9 participants at risk, and zero in the angiography-without-angioplasty group, with 10 at risk. Three other adverse events are reported in each group, without event details.

The registry describes exact confidence intervals and Fisher's exact testing as planned methods but does not report their results. Comparative analyses, secondary outcome results, participant flow, missing-data methods, and analysis populations are not reported in the registry record. The posted figures therefore support a limited description of observed safety events, not a complete statistical assessment of the trial's broader aims.