This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Study on Efficacy and Safety of Divaza in Patients With Chronic Cerebral Ischemia and Cognitive Disorders (NCT04370028), a registered phase not stated study. The primary outcome is Mean MoCA Score at Week 1 and the End of the 12-week Therapy.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04370028 |
| Phase | Phase not stated |
| Condition | Chronic Cerebral Ischemia |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 2583 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Materia Medica Holding |
| Results posted | Yes |
2. Clinical Question
Population
Adult outpatients with chronic cerebral ischemia and cognitive disorders. The study description identifies participants from 8 federal districts of the Russian Federation, with a reported enrollment of 2583.
Intervention
Divaza, taken orally as 2 tablet 3 times daily. The administration description says to keep the tablets in the mouth until completely dissolved, outside of meal.
Comparator
No like-for-like control comparison is described. The study is observational, and allocation is not stated in the registry record.
Primary question
How did the mean Montreal Cognitive Assessment score compare between week 1 and the end of the 12-week therapy period among participants included in the analysis?
The MoCA is described as a scale from 0 to 30, with higher scores meaning a better outcome. It is used to evaluate the presence of cognitive impairment. The registry lists a mean score at week 1 and at the end of therapy as the primary outcome, but it does not report the actual means, their standard deviations, or a numerical change between those timepoints. Scores were not reported for 21 patients at least at one timepoint, and those patients were excluded from the analysis. The record therefore identifies the clinical question and the analyzed outcome, but does not provide enough numerical outcome information to describe the magnitude or precision of the observed score pattern.
3. Trial Design
This was an open-label, prospective, observational, multicenter study of Divaza in patients with chronic cerebral ischemia and cognitive disorders. The record reports enrollment of 2583 and identifies the participants as adult outpatients from 8 federal districts of the Russian Federation. The study status is completed. The recorded start is 2016-10 and the primary completion is 2017-01.
The registry lists Divaza as the intervention and describes oral administration as 2 tablet 3 times daily, with the tablets kept in the mouth until completely dissolved, outside of meal. These are the recorded administration instructions; adherence and actual exposure by participant are not reported in the registry record.
Observational design means the study record does not describe random assignment to treatment. Allocation is not stated, and no like-for-like control arm is described. Consequently, the primary outcome is a score comparison across time in the study group, rather than a randomized comparison of Divaza with another treatment or with no treatment. Open-label means treatment was not masked in the study description; details about who knew the treatment status and how outcome assessment was conducted are not reported in the registry record.
The primary outcome is the mean MoCA score at week 1 and at the end of the 12-week therapy period. The registry also lists secondary MoCA outcomes, including score thresholds, mean score dynamics by age group, and improvement by age group. Seven outcome measures and 8 analyses are recorded. The protocol’s sample-size justification, a detailed statistical analysis plan, and any interim analysis plan are not reported in the registry record.
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
| Stage | Divaza Treatment Group |
|---|---|
| STARTED | 2583 |
| COMPLETED | 1876 |
| NOT COMPLETED | 707 |
Reasons for not completing this period:
| Reason | Divaza Treatment Group |
|---|---|
| Withdrawal by Subject | 695 |
| Protocol Violation | 9 |
| Adverse Event | 3 |
Analysis population for the primary outcome, as defined in the registry: MoCA scores were not reported in 21 patients at least at one timepoint (excluded from analysis)
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: Safety was assessed using the data of all 2583 patients. Within each efficacy and demographic analysis only complete cases approach was used, therefore the number of patients analyzed in efficacy analysis was fewer than 1876
| Characteristic | Unit | Divaza Treatment Group |
|---|---|---|
| Participants analysed | 1876 | |
| Age, Continuous | years | 65.7 (SD 19.1) |
| Age, Customized: Young (<35 yo) | participants | 25 |
| Age, Customized: Middle aged (35-59 yo) | participants | 501 |
| Age, Customized: Elderly (60-75 yo) | participants | 1062 |
| Age, Customized: Senile (75-90 yo) | participants | 265 |
| Sex: Female, Male: Female | Participants | 1139 |
| Sex: Female, Male: Male | Participants | 708 |
| Baseline MoCA score | units on a scale | 19.4 (SD 5.1) |
6. Primary Endpoint
The registry lists the primary outcome as Mean MoCA Score at Week 1 and the End of the 12-week Therapy, measured over week 1 to 12 week.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the mean Montreal Cognitive Assessment score at week 1 and at the end of the 12-week therapy period. MoCA is a cognitive assessment on a scale from 0 to 30; higher scores mean a better outcome. The registry describes the test as a way to evaluate the presence of cognitive impairment. A mean score provides a group-level description of performance, while the standard deviation describes how spread out individual scores are around that mean.
Assessing scores at more than one timepoint can describe how the measured outcome changes during follow-up. In this study, the listed comparison begins at week 1, not at a recorded pretreatment timepoint. The meaning of a score pattern therefore depends on the timing and context of measurement; it should not automatically be interpreted as change from before therapy.
The registry specifies the mean and standard deviation as the endpoint summary, but numerical values for either timepoint and a numerical contrast are not reported in the registry record. It also states that MoCA scores were not reported for 21 patients at least at one timepoint and that these patients were excluded from the analysis. Without the outcome values and their uncertainty, the magnitude and precision of the score pattern cannot be described from the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The study addresses a within-group question: the primary endpoint compares mean MoCA scores at week 1 and at the end of 12-week therapy in the Divaza treatment group. It does not describe a randomized comparison against a control group. Because allocation is not stated and the study is observational, a difference in scores over time, if present, would not by itself establish that Divaza caused that difference. Changes could also reflect factors not separated by the study design, including the passage of time, other care, participant characteristics, or measurement conditions. The registry record does not report these factors in enough detail to assess their role.
The endpoint’s scale runs from 0 to 30, and higher scores mean a better outcome. The registry identifies the mean and standard deviation as the summary measures, but does not report their values. It also does not report a numerical change, confidence interval, test statistic, or p-value for the primary endpoint. As a result, the posted record does not support a description of the direction, size, or statistical precision of the primary outcome. The endpoint’s definition alone is not evidence that scores increased or decreased.
The score comparison is specified from week 1 to the end of therapy. It therefore does not represent a comparison to a documented pretreatment baseline as described in the registry record. Any interpretation should stay within the timepoints named in the outcome definition. The record does not explain why week 1 was selected as the first measurement or provide a more detailed schedule of assessments.
For the primary analysis, scores were not reported for 21 patients at least at one timepoint, and those patients were excluded. The record does not describe whether the absence of scores was related to participant characteristics or outcomes. If participants with missing scores differ from those included, a mean based on analyzed participants may not reflect the full enrolled group. This is a general concern about analysis populations, not evidence that such a difference occurred in this study.
The secondary outcomes add other ways to describe MoCA: the number of patients below a score threshold at 12 weeks, the number at or below another threshold at the end of therapy, mean-score dynamics by age group, and score improvement by age group. Numerical findings for these outcomes are not reported in the registry record. The existence of named outcome measures does not establish that a particular result was observed, nor does it show how uncertainty or multiple analyses were handled.
For those reasons, the registry record supports a description of the study question, design, and outcome definitions, but not a conclusion about the magnitude or precision of cognitive-score results. Statistical interpretation requires the actual estimates and their uncertainty, alongside an understanding of missing data and the limitations of an observational, uncontrolled design.
9. Statistical Methods Explained
The primary outcome is a continuous measure summarized by a mean and standard deviation. General statistical interpretation of a mean focuses on the average score in the analyzed group. The standard deviation describes the spread of individual scores around that average; it is not itself a measure of uncertainty in the estimated mean. The registry names these summary measures but does not report their numerical values.
What does a mean score describe?
General: a mean condenses the scores in a group into a single average. It can be useful for describing a group’s overall level, but it does not show the full distribution of scores. Participants may have scores clustered near the mean or spread widely around it. A mean should therefore be read with a measure of variability and with the scale’s meaning in mind. Here, the scale is 0 to 30, and higher MoCA scores mean a better outcome. No actual mean or standard deviation is reported in the registry record, so the group’s level and variability cannot be characterized numerically.
A mean change across time can summarize the difference in group averages between assessment points. General: a group mean difference is not necessarily the same as the average of individual participant changes if different participants contribute at different times. The registry states that MoCA scores were not reported for 21 patients at least at one timepoint and that these patients were excluded from analysis, but it does not describe the calculation used for the timepoint comparison. It is therefore not possible to determine from the record how the paired observations were handled or whether any other analysis choices were made.
How should uncertainty be understood?
General: a confidence interval describes a range of values compatible with the data and a specified statistical procedure. A narrower interval indicates greater precision under that procedure; a wider interval indicates less precision. A confidence interval does not resolve potential bias from study design, missing outcomes, or measurement. No confidence interval for the primary MoCA outcome is reported in the registry record. The mean and standard deviation are also not reported, so the precision of the estimate cannot be assessed from those summaries.
General: a hypothesis test can assess how compatible the observed data are with a specified null hypothesis under a model. A p-value does not measure the size or clinical importance of an effect, and it does not establish causation. The registry record does not report a test method or p-value for the primary outcome. The named outcome and the description of mean and standard deviation do not identify which inferential procedure, if any, was used.
What does the study design allow?
General: random assignment can help balance measured and unmeasured factors between treatment groups, while a control group can provide a concurrent comparison. This study is described as observational and open-label, and allocation is not stated. No like-for-like control comparison is described. A before-and-after score pattern in one group can be informative descriptively, but it cannot separate a treatment effect from other explanations without additional design or analysis information. No adjustment strategy for potential confounding is reported in the registry record.
Open-label status also matters for interpretation. General: when treatment status is known, expectations or assessment conditions may influence measured outcomes, depending on how the outcome is collected. This is a possible design consideration, not evidence that measurement was biased in this study. The registry does not describe assessor masking, assessment procedures, or steps taken to limit measurement bias.
What is over-dispersion, and is it relevant?
General: over-dispersion occurs when count data vary more than a statistical model assumes. It can make standard errors too small if a model fails to account for that extra variability. The primary endpoint is a continuous MoCA score summarized by a mean and standard deviation, rather than a count outcome. The registry record does not identify the model used for the primary outcome, so it is not possible to say whether an over-dispersion issue arose in any analysis. The concept is most relevant to count outcomes if their analysis uses a model with a variance assumption.
The secondary outcomes include counts of patients meeting MoCA thresholds and counts of patients with score improvement in age groups, as well as mean-score dynamics by age group. Those definitions indicate different forms of summaries, but the record does not report the numerical findings or the statistical methods used to analyze them. No model, covariate adjustment, handling of repeated measures, or subgroup-analysis procedure is reported in the registry record.
How should planning calculations be read?
General: sample-size calculations are planning tools that estimate the number of participants needed under stated assumptions about the effect to detect, statistical significance level, allocation, and analysis method. They are not evidence that an effect occurred, and they are not observed power. The registry’s sample-size assumptions describe a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event calculations, the assumption describes total events, while other calculations describe participants per arm. These are planning assumptions, not the design of this observational study. The protocol’s own sample-size justification is not reported in the registry record, and the study description does not include a two-arm randomized comparison.
These general concepts help distinguish description, uncertainty, and causal interpretation. For this study, the record identifies the measure and timepoints but does not report the numerical primary results or a detailed analysis plan. Therefore, statistical conclusions about the measured score pattern cannot be reconstructed from the outcome definition alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists seven outcome measures and 8 analyses. It names the primary mean MoCA score at week 1 and at the end of therapy, and lists secondary outcomes concerning MoCA thresholds, age-group mean-score dynamics, and improvement by age group. The methods used for the analyses and any adjustment for multiple comparisons are not reported in the registry record.
General: when several outcomes or analyses are examined, the chance of obtaining at least one apparently unusual result can increase, depending on how the analyses are related and how results are interpreted. Adjustment methods can address some multiplicity concerns, but they do not remove limitations in study design or data quality. Without a reported analysis plan or multiplicity approach, it is not possible to determine how the outcomes were prioritized or how any statistical evidence should be interpreted across them.
The record states that MoCA scores were not reported for 21 patients at least at one timepoint and that these patients were excluded from analysis. The reason for missing scores, the distribution of missingness across assessment times, and any sensitivity analyses are not reported in the registry record. General: excluding participants with incomplete measurements can affect estimates if their outcomes differ systematically from those of participants included in the analysis. This is a potential concern, not a claim that such a difference occurred.
The analysis population is described only to the extent that those 21 patients were excluded. Further details about the analyzed population, adherence, other exclusions, imputation, or handling of incomplete observations are not reported in the registry record. The primary outcome’s actual estimates and uncertainty are also not reported, limiting interpretation of both the results and the effect of missing data.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Divaza Treatment Group | 0 | 2583 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Divaza Treatment Group | 0 of 2583 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Divaza Treatment Group | 17 of 2583 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Divaza Treatment Group |
|---|---|---|
| Nausea | Gastrointestinal disorders | 3 of 2583 |
| Dizziness | Nervous system disorders | 3 of 2583 |
| Headache | Nervous system disorders | 2 of 2583 |
| Pruritus | Skin and subcutaneous tissue disorders | 2 of 2583 |
| Rash | Skin and subcutaneous tissue disorders | 2 of 2583 |
| Somnolence | Nervous system disorders | 1 of 2583 |
| Insomnia | Psychiatric disorders | 1 of 2583 |
| Tinnitus | Ear and labyrinth disorders | 1 of 2583 |
| Dry mouth | Gastrointestinal disorders | 1 of 2583 |
| Rash pruritic | Skin and subcutaneous tissue disorders | 1 of 2583 |
The registry lists 2583 participants at risk for serious adverse events in the Divaza Treatment Group and 0 affected. It lists 2583 at risk for other adverse events and 17 affected. The recorded number of deaths is 0. No top serious adverse event terms are listed.
These figures describe the registry’s reported counts. A count of 0 affected for serious adverse events should be read as no serious events recorded in this outcome entry, not as proof that the risk of serious events is absent. The record does not provide additional detail about event definitions, event ascertainment, follow-up completeness, or whether events were considered related to treatment. The absence of listed serious terms means that no top serious terms are reported in the record; it does not supply further clinical detail about monitoring.
The other-adverse-event count is separate from the serious-event count. The figures do not establish whether the events were caused by Divaza, and they do not describe severity or individual event types. They should be interpreted as recorded counts within this observational study, not as a comparison of safety against another group, because no like-for-like control comparison is described.
12. What the Result Does, and Does Not, Mean
The record establishes that a completed, open-label, prospective, observational, multicenter study examined Divaza in adult outpatients with chronic cerebral ischemia and cognitive disorders. It identifies the primary outcome as mean MoCA score at week 1 and at the end of the 12-week therapy period, and defines the scale’s direction: higher scores mean a better outcome. It also gives the reported enrollment and describes the administration instructions.
Those details explain what was studied, but the registry record does not report the primary MoCA means, standard deviations, or numerical difference between the stated timepoints. It therefore does not show whether the mean score increased, decreased, or remained similar, nor how precisely any estimate was made. Named secondary outcomes likewise do not establish their findings; numerical results for them are not reported in the registry record.
The study’s observational design and lack of a described control comparison also limit causal interpretation. A time-related change, if one were reported, would describe the observed group over follow-up. Without a concurrent comparison and more information about other influences, the record would not establish that the intervention caused the change.
The safety entries report 0 serious adverse events among 2583 at risk, 17 other adverse events among 2583 at risk, and 0 deaths. Those are registry counts, not evidence about comparative risk or treatment causation. Overall, the record supports a clear description of the study question and some design and safety details, but it does not provide the numerical primary outcome results needed to characterize the cognitive-score findings or their precision.
13. Why This Trial Matters Statistically
This study illustrates why the design and the result need to be read together. A mean MoCA score can describe cognitive-assessment performance in the enrolled group, and repeated measurements can describe scores at more than one point in follow-up. But the primary outcome is a comparison of week 1 with the end of 12-week therapy, and the record does not describe a randomized control group. That distinction matters: a change over time is not automatically a treatment effect.
The registry also makes the analysis population relevant. MoCA scores were not reported for 21 patients at least at one timepoint, and those patients were excluded. Even when a missing-data count is stated, readers need information about why measurements are missing and how exclusions affect the analysis to judge the reliability of estimates. Such details are not reported in the registry record.
Finally, outcome definitions are not outcome findings. The record identifies the scale, the primary timepoints, and several secondary MoCA outcomes, but numerical MoCA results and their uncertainty are not reported. Statistical interpretation depends on effect estimates and precision, not only on the name of an endpoint or the number of analyses. The study is therefore useful for examining how an observational registry entry frames a clinical question, while also showing why cautious conclusions require both transparent results and a design that supports the intended inference.
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 design limitation is the absence of a described like-for-like control comparison. The study is observational, and allocation is not stated. As a result, score patterns over time cannot be separated from other possible influences using the design information reported in the registry. The open-label description also leaves the assessment process unclear; assessor masking and procedures for minimizing measurement bias are not reported in the registry record.
The first primary measurement is specified at week 1, with the later measurement at the end of 12-week therapy. A pretreatment MoCA score is not named in the primary outcome definition, and the reason for selecting week 1 as the first timepoint is not reported in the registry record. This limits what can be inferred about change from before therapy.
Missing outcome information is another limitation. Scores were not reported for 21 patients at least at one timepoint, and those patients were excluded from analysis. Reasons for missingness, any imputation, and sensitivity analyses are not reported. The numerical primary results, including means, standard deviations, and uncertainty, are also not reported in the registry record.
The study description identifies adult outpatients with chronic cerebral ischemia from 8 federal districts of the Russian Federation. Further details about participant characteristics and the extent to which the enrolled group reflects other patient settings are not reported. The registry names secondary outcomes and records seven outcome measures and 8 analyses, but does not describe the full analysis plan or handling of multiplicity. These gaps limit assessment of the findings’ robustness and applicability.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study on Efficacy and Safety of Divaza in Patients With Chronic Cerebral Ischemia and Cognitive Disorders — NCT04370028.
- Registry record last updated 2021-03-10; status last verified 2020-04.
- Results first posted 2021-03-10.
- 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.
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18. Record Summary
The registry record describes a completed, open-label, prospective, observational, multicenter study of Divaza in adult outpatients with chronic cerebral ischemia and cognitive disorders. Reported enrollment was 2583, with participants from 8 federal districts of the Russian Federation. The recorded start was 2016-10 and primary completion was 2017-01.
The primary outcome is mean MoCA score at week 1 and at the end of the 12-week therapy period. MoCA ranges from 0 to 30, with higher scores meaning a better outcome. Scores were not reported for 21 patients at least at one timepoint, and those patients were excluded from analysis. Numerical primary outcome results are not reported in the registry record.
Safety entries list 0 serious adverse events among 2583 at risk, 17 other adverse events among 2583 at risk, and 0 deaths. The record does not describe a like-for-like control comparison, and allocation is not stated.