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

• ADAS-cog+ at 3 and 12 months (change from baseline) [ Time Frame: 3 and 12 months ] [ Designated as safety issue: No ]
• MoCA at end of infusion period, 3, 6 and 12 months (change from baseline) [ Time Frame: 3, 6 and 12 months ] [ Designated as safety issue: No ]

  Montreal Cognitive Assessment Scale (MoCA) measures a score of ≤ 25 points:

  • 4-9 school years ≤ 23 points,
  • 10-12 years ≤ 24 points
  • >12 years ≤ 25 points
• ADAS-cog+ responders at time points 3, 6 and 12 months [ Time Frame: 3, 6 and 12 months ] [ Designated as safety issue: No ]
• Diagnosis of dementia [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
  Diagnosis of dementia will be evaluated after 6 and 12 months classified according to International Statistical Classification of Diseases and related Health Problems (ICD-10) (Classification of Mental and Behavioural Disorders, Diagnostic Criteria for Research)
• NIHSS at end of infusion period, 3, 6 and 12 months (relative change from baseline) [ Time Frame: 3, 6 and 12 months ] [ Designated as safety issue: No ]
  National Institutes of Health Stroke Scale (NIHSS) measures a score between 3 and 18.
• Barthel Index at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  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, moving from wheelchair to bed and return, grooming, transferring to and from a toilet, bathing, walking on level surface, going up and down stairs, dressing, continence of bowels and bladder.
• EuroQol EQ-5D (EQ-5D) at 6 and 12 months [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]

  The measurement of states of health is crucial in determining the outcomes of health care. The EuroQoL EQ-5D questionnaire was developed as a generic state of health measure and describes states of health in five dimensions: mobility, self care, usual activities, pain or discomfort, and anxiety or depression.

  EQ-5D is a standardised measure of health status. 5 dimensions: mobility, self care, usual activities, pain/discomfort, anxiety/depression.

  each dimension now has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems

• Beck Depression Inventory, version II (BDI-II) at 3, 6 and 12 months [ Time Frame: 3, 6 and 12 months ] [ Designated as safety issue: No ]

  BDI II scale:

  • 0-13 minimal depression
  • 14-19 mild depression
  • 20-28 moderate depression
  • 29-63 severe depression

The aim of this trial is to provide evidence that Actovegin has a symptomatic effect in subjects with post stroke cognitive impairment (PSCI) during a six month treatment period compared to subjects administered placebo. Subjects will receive IV infusions whilst in hospital, and tablets once discharged. Subjects will be followed up for a further six months after their treatment is stopped to explore if the cognitive symptoms of the subjects treated with Actovegin show sustained improvement. The trial will also explore the possible prevention of dementia with Actovegin in patients who have suffered a recent ischaemic stroke, as well as the effect of Actovegin on other stroke outcomes. Safety information on Actovegin will be collected.

• Drug: Actovegin
  • Actovegin 8mg/mL Solution for Infusion (0.9% NaCl) (250mL / 2000 mg / intravenously (IV) / day) up to 20 days
  • Actovegin 200 mg tablets as 2 tablets 3 times daily from the day after the end of infusions and for the remainder of the 6-month treatment period.
• Drug: Placebo
  • Actovegin placebo Solution for Infusion (0,9% NaCl) (250 mL / IV / day) up to 20 days
  • Actovegin placebo tablets as 2 tablets 3 times daily from the day after the end of infusions and for the remainder of the 6-month treatment period.

• Active Comparator: Actovegin
  Intervention: Drug: Actovegin
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

Main Inclusion Criteria:

• Subject has suffered a recent supra-tentorial ischaemic stroke supported by CT scan or MRI findings (in accordance with local practice).
• Subject is male or female, aged 60 years or above.
• Subject has a score on the National Institute of Health Stroke Scale (NIHSS) between 3 and 18 (inclusive)
• Subject is capable of completing the Montreal Cognitive Assessment (MoCA) and has a score of ≤ 25 points with adjustment for level of education (4-9 school years ≤ 23 points, 10-12 years ≤ 24 points, >12 years ≤ 25 points)

Main Exclusion Criteria:

• Subject has a medical history of dementia
• Subject has a known medical history of major depression or psychotic disorder
• Subject is indicated for treatment with thrombolytics or carotid surgery as the current standard of care

Randomisation Criteria

• Inclusion Criteria
• Ability to perform ADAS-cog+
• Exclusion Criteria
• Clinically there is suspicion of progressive stroke