Safety and Efficacy of Sequential Therapy With Mexidol® in Patients With Chronic Cerebral Ischemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of Sequential Therapy With Mexidol® in Patients With Chronic Cerebral Ischemia (NCT06834490), a randomized phase 3 study. The primary outcome is Mean Score of Montreal Cognitive Assessment (MoCA) at Visit 5 in Comparison With Reference Score at Visit 0.

2. Clinical Question

3. Trial Design

MEMO is described as an international multicentre, randomized, double-blind, placebo-controlled Phase 3 trial with a parallel-group design and an adaptive design. The registry lists Pharmasoft as sponsor and the condition as chronic cerebral ischemia. The study status is completed. Its recorded start date is 2019-11-05, and its primary completion date is 2020-12-08.

Enrollment was 318. Participants were assigned to a main Mexidol group or a placebo control group. The treatment sequence had an intravenous phase followed by an oral phase. The active regimen was intravenous Mexidol once daily for 14 days, followed by oral Mexidol FORTE 250 three times a day for 60 days. The placebo regimen was described as matching both phases of active treatment.

Randomization and double masking are features that can help limit systematic differences in treatment assignment and assessment. A placebo comparator also gives the trial a way to compare outcomes between groups receiving the same sequence of treatment procedures, with active medication in one group and matching placebo in the other. These are general design principles; the registry does not describe the methods used to generate or conceal the randomization sequence, or how masking was maintained.

The official title identifies the trial as adaptive, but the particular adaptive procedures, decision rules, and timing of any adaptations are not reported in the registry record. Nor does the record explain whether the design changed during conduct. Those details should not be inferred from the design label alone. Numerical results for the primary endpoint and analysis estimates are also not reported in the registry record, so the trial design can be described without making a claim about the comparative result.

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: Of 330 screened participants, 318 met inclusion criteria and were randomized to treatment.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The efficacy analysis was performed for ITT-population excluding participant No. 098 whose data after the randomization visit are missing.

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: ITT-population was used for description of baseline measures.

6. Primary Endpoint

The registry lists the primary outcome as Mean Score of Montreal Cognitive Assessment (MoCA) at Visit 5 in Comparison With Reference Score at Visit 0, measured over Day 75+2 (Visit 5) compared with the baseline level (Visit 0, 7 days before treatment).

The primary endpoint is the mean MoCA score at Visit 5 compared with the reference score at Visit 0. Visit 5 is specified as Day 75+2; Visit 0 is described as 7 days before treatment. The MoCA is used to assess the degree of cognitive impairment in patients with CCI. Its scores range from 0 to 30, and a score of 26 or over is considered normal. The registry description states that a higher score than at Visit 0 is expected after treatment.

As a general measurement principle, a cognitive assessment can turn performance on standardized tasks into a score that can be compared across visits and between randomized groups. A mean summarizes the average score in the analysis population, while the standard deviation describes the spread of individual scores around that mean. A change in a mean can describe group-level movement, but it does not show that every participant changed in the same way.

The endpoint is a score on a scale, not a direct count of daily functioning or a diagnosis by itself. The registry record does not report the mean scores, standard deviations, treatment-group contrast, or uncertainty for this endpoint. It therefore does not show how the observed MoCA results compare with the reference score or how precisely any between-group contrast was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean endpoint describe?

The primary outcome is continuous: MoCA is recorded as a numerical score on a scale. A group mean gives a summary of scores across participants in the analysis population. The standard deviation describes how much those individual scores vary around the mean. These answer different questions: the mean describes the average level, while the standard deviation describes dispersion. A difference in group means, if reported, would summarize an average contrast, not the experience of every participant.

As a general statistical point, continuous outcomes are often analyzed with methods that compare group averages, possibly accounting for baseline scores or other prespecified variables. The registry record does not report the specific model, covariate adjustments, or other analytic details used for the primary outcome. No particular model should be assumed. It also does not report a primary treatment estimate or its standard error, confidence interval, or p-value.

Why does variability matter?

General explanation: the standard deviation is relevant because participants can have different baseline scores and different changes over time. If scores vary substantially, an average contrast may be estimated less precisely than when scores are more tightly clustered, all else being equal. The standard deviation is not itself a measure of the treatment effect. For this trial, the registry identifies standard deviation as the measure of dispersion but does not report the endpoint values needed to evaluate the observed variability.

General explanation: over-dispersion occurs when the observed variation is greater than a statistical model expects. When that happens, standard errors and uncertainty estimates from a model that assumes less variability can be too small, making findings appear more precise than warranted. That concept is not evidence that over-dispersion occurred in this trial. The registry record does not report model diagnostics or information that would establish whether it was relevant.

What would an interval or test contribute?

General explanation: a confidence interval accompanies an estimate by showing uncertainty around it under the analysis assumptions. A relatively narrow interval indicates more precise estimation than a wider interval, but interpretation also depends on the values included and on the clinical context. A p-value evaluates how compatible the data are with a null hypothesis under a specified model; it does not give the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. Neither a confidence interval nor a p-value is reported for the primary endpoint in the registry record.

For a randomized comparison, the primary statistical question is usually the contrast between groups, rather than whether a change within one group alone differs from zero. A within-group change can reflect many influences, including time and background care. The registry states that the mean at Visit 5 is compared with the reference score at Visit 0, but it does not report how the comparative analysis was formulated. It is therefore not possible to tell whether the primary analysis used change scores, an endpoint model adjusted for baseline, or another approach.

What does the planning illustration mean?

The trial's sample-size assumptions describe planning illustrations based on the observed effect, with two-sided significance level 0.05, equal allocation, and a normal approximation. They are not described as the original trial design justification. In general, sample-size planning asks how many participants per arm would be needed to detect an effect of a specified size under chosen assumptions. Such numbers are planning illustrations, not observed power and not evidence that an effect was found. The registry record does not report the original sample-size justification or the statistical basis for the trial's enrollment target.

The assumptions describe the effect to detect as a stated fraction of the observed effect. Because the registry record does not report the primary observed effect, it does not permit independent interpretation of the effect scale that underlies such illustrations. The listed assumptions should not be mistaken for the trial's actual analysis plan, and an illustrative sample size cannot repair missing outcome reporting.

What can be inferred from the design labels?

Randomized allocation, double masking, and parallel groups describe the broad structure of the trial. They do not reveal the precise statistical methods. The title also calls the trial adaptive, but the registry record does not report adaptation rules, interim analysis procedures, or how any adaptation would affect error rates or the final analysis. General statistical practice can address those design questions, but trial-specific answers cannot be posted without the relevant methods details.

The number of analyses reported in the registry is 0. This does not mean that no analyses were performed; it means the record does not provide analysis entries. As a result, the statistical interpretation is limited to the design and outcome definitions recorded, along with the adverse-event counts. Numerical estimates, uncertainty measures, and model diagnostics are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes, including cognitive impairment, physical and mental quality of life, fatigue, anxiety, autonomic changes, and motor function. It also identifies multiple visits for some measures. When a study evaluates many outcomes, time points, or contrasts, the chance of at least one apparently notable finding can increase. General approaches to multiplicity include prespecifying a hierarchy, adjusting significance thresholds, or treating secondary comparisons as exploratory. The registry record does not report whether any multiplicity strategy was planned or used, nor does it report secondary outcome results.

The efficacy population is described as ITT-population excluding participant No. 098, whose data after the randomization visit are missing. The record does not explain the missing-data method, whether any other observations were incomplete, or whether sensitivity analyses were conducted. General methods can include likelihood-based models, imputation, or sensitivity analyses under alternative assumptions, but none can be attributed to this trial from the registry record.

The record's use of the ITT label alongside an exclusion should be read precisely: the stated efficacy analysis excluded that participant. It is not possible to assess the effect of that exclusion without knowing the analysis details and outcome data. The registry record also does not report a per-protocol population or other analysis populations. Consequently, the robustness of the primary estimate to missingness, population definitions, or multiple comparisons cannot be judged.

11. 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 1% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events for 0 of 159 participants in the Main (Mexidol) group and 0 of 159 in the Control (Placebo) group. Deaths are reported as 0 in each group. Other adverse events are reported for 19 of 159 participants in the Mexidol group and 32 of 159 in the placebo group. These are the counts recorded for the groups, not estimates adjusted for participant characteristics or exposure.

Counts alone do not show the type, timing, duration, severity, or relatedness of events. The registry record does not list serious adverse-event terms, and it does not provide event-level descriptions for the other adverse events. It also does not report a statistical comparison or uncertainty interval for these safety counts. A zero count in the record is not proof that an event is impossible or that all relevant events were captured. The figures describe reported events during the recorded trial, and should not be treated as a definitive comparative safety conclusion.

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

The registry record establishes that MEMO was designed as a randomized, double-blind, placebo-controlled, parallel-group Phase 3 trial of sequential Mexidol treatment in CCI. It specifies the treatment schedule, the MoCA endpoint, and the general timing of the primary assessment. It also records adverse-event counts. These registry entries describe what was planned and what was entered in the record; they do not provide the numerical efficacy result.

The primary endpoint description identifies an expected higher MoCA score after treatment, but an expectation is not an observed finding. Because group means and a treatment contrast are not reported in the registry record, the record does not show whether scores changed, how the groups compared, or how precise that comparison was. It does not support a conclusion that the treatment did or did not improve cognition.

Likewise, the posted adverse-event counts are descriptive. They do not provide enough detail to infer the comparative likelihood or nature of harm. General statistical interpretation requires attention to event definitions, observation time, completeness of reporting, and uncertainty; trial-specific information on these matters is not reported in the registry record.

These limits are about what can be concluded from the registry record, not a claim that analyses were never performed. The record reports 0 analyses, but does not establish why outcome estimates are absent. The statistical distinction is important: a completed trial record can document design and conduct details while leaving the central effect estimate unavailable. Conclusions about the comparative outcome require the numerical results and analysis methods, which are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of why design descriptions and outcome reporting serve different purposes. Randomization, masking, a placebo comparator, and a parallel-group structure describe safeguards and the intended comparison. They do not indicate the direction, magnitude, or precision of the outcome. For interpretation, the primary group contrast and its uncertainty are essential, but those results are not reported in the registry record.

The endpoint also illustrates why the measurement plan matters. MoCA is a continuous cognitive score with a stated scale range and a reference assessment before treatment. A mean can summarize group performance, but the analysis must clarify how baseline and follow-up scores were compared, how missing observations were handled, and what uncertainty accompanies the estimate. The registry does not report those analytic details.

The trial title identifies an adaptive design, which makes the absence of design-specific methods particularly relevant for statistical interpretation. Adaptation can involve different procedures, and the label alone does not reveal what decisions were planned or how the final analysis accounted for them. The registry record does not report those details, so no particular adaptive method can be evaluated.

Finally, the record demonstrates the limits of descriptive safety counts. Event counts are useful context, but counts without definitions, event descriptions, and comparative uncertainty do not settle a safety comparison. The broader lesson is that transparent reporting of estimates, uncertainty, analysis populations, missing-data methods, and decision rules is needed to assess how much a trial's results support its research question.

14. Limitations

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

The main trial-specific limitation for interpretation is the absence of numerical results for the primary MoCA endpoint. The registry record does not report group means, standard deviations, a treatment contrast, a confidence interval, or a p-value. It also does not report numerical results for the listed secondary outcomes. As a result, neither the magnitude nor precision of the intended efficacy comparison can be assessed from this record.

The efficacy population is described as ITT-population excluding participant No. 098 because post-randomization visit data were missing. The record does not explain the exclusion rationale beyond the missing data, the handling of missing observations, or whether sensitivity analyses were used. It also does not provide the analysis model or details of baseline adjustment. These omissions limit assessment of potential bias and robustness.

Although the official title identifies an adaptive design, the adaptation rules, interim procedures, and statistical consequences are not reported in the registry record. The original sample-size justification and detailed statistical plan are also not reported. The existence of a planning illustration does not disclose the original design rationale or substitute for outcome estimates.

Safety information is limited to group counts. The record does not list serious adverse-event terms or provide event-level detail for other adverse events. It does not report comparative safety estimates or their uncertainty. These reporting limitations constrain interpretation of both benefit and harm and should not be replaced by assumptions about methods or outcomes.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Efficacy of Sequential Therapy With Mexidol® in Patients With Chronic Cerebral Ischemia — NCT06834490.
• Registry record last updated 2025-10-06; status last verified 2025-09.
• Results first posted 2025-10-06.
• 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.

18. Record Summary

MEMO is a completed randomized, double-blind, placebo-controlled, parallel-group Phase 3 trial of sequential Mexidol therapy for chronic cerebral ischemia. Enrollment was 318. The active regimen included intravenous Mexidol for 14 days followed by oral Mexidol FORTE 250 for 60 days; the control group received matching placebo in both phases.

The primary endpoint was mean MoCA score at Visit 5 compared with the reference score at Visit 0. Numerical primary and secondary outcome results are not reported in the registry record. The efficacy analysis population is described as ITT-population excluding participant No. 098 because data after randomization were missing. Serious adverse events and deaths were reported as 0 in each group; other adverse events were reported for 19 participants in the Mexidol group and 32 in the placebo group, with 159 at risk in each group.