Efficacy and Safety of Actovegin in Post-stroke Cognitive Impairment (PSCI)

The ADAS-cog measures cognitive performance by combining the ratings of 11 items. The cognitive domains mainly addressed by ADAS-cog are: memory (short term), language, ability to orientate (reflects memory), construction/planning of simple designs and performance. The extended version of the ADAS-cog (ADAS-cog+) includes 3 additional items: a 2-number cancellation task to test for attention, a delayed recall task to test for memory consolidation and a maze test for executive performance. Each item is scored and then the item scores are totaled. Total scores range from 0 (best) to 90 (worst). Higher scores indicate greater cognitive impairment. A negative change from Baseline indicates improvement. Analysis of Covariance (ANCOVA) model was used for analyses that included treatment, pooled centre, and their interaction as factors and Baseline ADAS-cog+ score as a covariate.

Time frame: Baseline and Month 6

Population: Intent-to-treat population, all enrolled participants who received at least one dose of study drug, with data available for analysis. Missing individual item scores (where only some item scores missing) imputed with worst possible score and missing total scores (where all item scores missing) imputed by last observation carried forward.

The Barthel Index consists of 10 items that measure a person's daily functioning, specifically the activities of daily living and mobility. The items include: feeding, transfers (bed to chair and back), grooming, toilet use, bathing, mobility (walking on level surface), going up and down stairs, dressing, continence of bowels and bladder. Each performance item is rated, with a given number of points assigned to each level or ranking. Individual scores are summed for a total possible scores ranging from 0 (worst) to 100 (best) with higher scores indicating more independent daily living.

Time frame: Months 3 and 6

Population: Participants from the Intent-to-treat population, all enrolled participants who received at least one dose of study drug, with data available for analyses at the given time-point.

The BDI-II is a 21-question multiple-choice self-report inventory for measuring the severity of depression. is composed of items relating to symptoms of depression such as hopelessness and irritability, cognitions such as guilt or feelings of being punished, as well as physical symptoms such as fatigue, weight loss, and lack of interest in sex. Each answer is scored on a scale 0 (best) to 3 (worst). Total scores range from 0 to 63 with higher scores indicating more severe depression. BDI II scale: * 0-13 minimal depression * 14-19 mild depression * 20-28 moderate depression * 29-63 severe depression

Time frame: Months 3, 6 and 12

Population: Participants from the Intent-to-treat population, all enrolled participants who received at least one dose of study drug, with data available for analyses at the given time-point.

The ADAS-cog measures cognitive performance by combining the ratings of 11 items. The cognitive domains mainly addressed by ADAS-cog are: memory (short term), language, ability to orientate (reflects memory), construction/planning of simple designs and performance. The extended version of the ADAS-cog (ADAS-cog+) includes 3 additional items: a 2-number cancellation task to test for attention, a delayed recall task to test for memory consolidation and a maze test for executive performance. Each item is scored and then the item scores are totaled. Total scores range from 0 (best) to 90 (worst). Higher scores indicate greater cognitive impairment. A negative change from Baseline indicates improvement. ANCOVA model was used for analyses that included treatment, pooled centre, and their interaction as factors and Baseline ADAS-cog+ score as a covariate.

Time frame: Baseline and Months 3 and 12

Population: Intent-to-treat population, all enrolled participants who received at least one dose of study drug, with data available for analysis. Missing individual item scores (where only some item scores missing) imputed with worst possible score.

The MoCA is a rapid screening test to assess mild cognitive impairment. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Time to administer the MoCA is approximately 10 minutes. The total possible score is 0 to 30 points; a score of 26 or above is considered normal. A positive change from Baseline (BL) indicates improvement. ANCOVA model was used for analyses that included treatment and pooled centres as factors, plus years of education and baseline MoCA score as covariates.

Time frame: Baseline, End of Infusion and Months 3, 6 and 12

Population: Participants from the Intent-to-treat population, all enrolled participants who received at least one dose of study drug, with data available for analyses at the given time-point.

The NIHSS is a tool to objectively quantify the impairment caused by a stroke. The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 (normal) to 4 (some level of impairment). The individual scores from each item are summed in order to calculate total possible NIHSS score from 0 (best) to 42 (worst). A negative change from Baseline indicates improvement. ANCOVA model was used for analyses that included treatment and pooled centre as factors and Baseline NIHSS score as a covariate.

Time frame: Baseline and End of Infusion and Months 3, 6 and 12

Population: Participants from the Intent-to-treat population, all enrolled participants who received at least one dose of study drug, with data available for analyses at the given time-point.

EQ-5D is a standardized measure of health status consisting of 5 dimensions: mobility, self -care, usual activities, pain/discomfort and anxiety/depression. The participant rates their level of function in each area using a 5 point scale where 1=no problems (best) to 5=extreme problems (worst). The percentage of participants in each category is reported.

Time frame: Month 12

Population: Participants from the Intent-to-treat population, all enrolled participants who received at least one dose of study drug, with data available for analyses at the given time-point.

EQ-5D is a standardized measure of health status consisting of 5 dimensions: mobility, self -care, usual activities, pain/discomfort and anxiety/depression. The participant rates their level of function in each area using a 5 point scale where 1=no problems (best) to 5=extreme problems (worst). The percentage of participants in each category is reported.

Time frame: Month 6

Population: Participants from the Intent-to-treat population, all enrolled participants who received at least one dose of study drug, with data available for analyses at the given time-point.

The EuroQoL included a visual analogue scale where the subject marks how they feel at that moment on a scale from 0 (the worst health that can be imagined) to 100 (the best health that can be imagined).

Time frame: Months 6 and 12

Population: Participants from the Intent-to-treat population, all enrolled participants who received at least one dose of study drug, with data available for analyses at the given time-point.

Responder was defined as an improvement of 4 or more from baseline on the ADAS-cog+ scale using observed data. The proportion of responders was compared between treatments using a chi-square test.

Time frame: Baseline and Months 3, 6 and 12

Population: Participants from the Intent-to-treat population, all enrolled participants who received at least one dose of study drug, with data available for analyses at the given time-point.

Diagnosis of dementia will be evaluated after 6 and 12 months classified according to International Statistical Classification of Diseases and related Health Problems 10th Revision (ICD-10) \[Classification of Mental and Behavioural Disorders, Diagnostic Criteria for Research\]. The proportion of participants with dementia was compared between treatments using a Fisher's exact test.

Time frame: Month 6

Population: Participants from the Intent-to-treat population, all enrolled participants who received at least one dose of study drug, with data available for analyses at the given time-point.

Diagnosis of dementia will be evaluated after 6 and 12 months classified according to International Statistical Classification of Diseases and related Health Problems 10th Revision (ICD-10) \[Classification of Mental and Behavioural Disorders, Diagnostic Criteria for Research\].

Time frame: Month 6 and 12

Population: Participants from the Intent-to-treat population, all enrolled participants who received at least one dose of study drug, with data available for analyses at the given time-point.