A 12-month, International, Parallel Group, Randomised, Multi-centre, Double-blind, Placebo-controlled Trial to Examine the Effect of Actovegin® Treatment Given First Intravenously and Subsequently Orally Over 6 Months, in Subjects With Post-stroke Cognitive Impairment (PSCI).
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 503
- Locations
- 1
- Primary Endpoint
- Change From Baseline in Alzheimer's Disease Assessment Scale + Cognitive Subscale Extended Version (ADAS-cog+) at Month 6
Study Overview
Brief Summary
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 received IV infusions whilst in hospital, and tablets once discharged. Subjects were followed up for a further six months after their treatment had been stopped to explore if the cognitive symptoms of the subjects treated with Actovegin showed sustained improvement. The trial also explored the possible prevention of dementia with Actovegin in patients who had suffered a recent ischaemic stroke, as well as the effect of Actovegin on other stroke outcomes. Safety information on Actovegin was collected.
Detailed Description
The drug tested in this study is called actovegin. Actovegin was tested to treat people who have post stroke cognitive impairment. This study looked at the improvement of cognitive symptoms in people who take actovegin compared to placebo.
The study enrolled 503 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which remained undisclosed to the patient and study doctor during the study:
- Actovegin-2000 mg intravenous solution; 2- 200 mg tablets 3 times a day
- Placebo intravenous solution; tablets (dummy inactive) - this is a solution or tablet that looks like the study drug but has no active ingredient
All participants received daily intravenous infusions in the hospital (up to a maximum of 20 infusions) followed by 2-200 mg tablets three times a day for the remainder of the 6-month treatment period.
This multi-centre trial was conducted in Belarus, Kazakhstan and Russia. The overall time to participate in this study was 12 months. Participants made multiple visits to the clinic plus a final visit after receiving their last dose of study drug for a follow-up assessment.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 60 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Participant has suffered a recent supra-tentorial ischaemic stroke supported by computed tomography (CT) scan or magnetic resonance imaging (MRI) findings (in accordance with local practice).
- •Participant is male or female, aged 60 years or above.
- •Participant has a score on the National Institute of Health Stroke Scale (NIHSS) between 3 and 18 (inclusive).
- •Participant 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).
Exclusion Criteria
- •Participant has a medical history of dementia.
- •Participant has a known medical history of major depression or psychotic disorder.
- •Participant is indicated for treatment with thrombolytics or carotid surgery as the current standard of care.
- •Randomisation Criteria:
- •Inclusion Criteria.
- •Ability to perform Alzheimer's Disease Assessment Scale + Cognitive Subscale Extended Version (ADAS-cog+).
- •Exclusion Criteria.
- •Clinically there is suspicion of progressive stroke.
Arms & Interventions
Actovegin
Actovegin 2000 mg solution, intravenous (IV) infusion for up to 20 days followed by 2 actovegin 200 mg, tablets, orally, 3 times a day for up to 6 months.
Intervention: Actovegin (Drug)
Placebo
Actovegin placebo-matching solution, intravenous (IV) infusion for up to 20 days followed by 2 actovegin placebo-matching, tablets, orally, 3 times a day for up to 6 months.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Change From Baseline in Alzheimer's Disease Assessment Scale + Cognitive Subscale Extended Version (ADAS-cog+) at Month 6
Time Frame: Baseline and Month 6
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.
Secondary Outcomes
- Percentage of ADAS-cog+ Responders at Time Points 3, 6 and 12 Months(Baseline and Months 3, 6 and 12)
- Barthel Index at Months 3 and 6(Months 3 and 6)
- EuroQol EQ-5D (EQ-5D) General Health at Months 6 and 12(Months 6 and 12)
- Change From Baseline in Montreal Cognitive Assessment Scale (MoCA) at End of Infusion Period, Months 3, 6 and 12(Baseline, End of Infusion and Months 3, 6 and 12)
- Beck Depression Inventory, Version II (BDI-II) at Months 3, 6 and 12(Months 3, 6 and 12)
- Change From Baseline in ADAS-cog+ at Month 3 and Month 12(Baseline and Months 3 and 12)
- Percentage of Participants With a Diagnosis of Dementia(Month 6 and 12)
- Change From Baseline in National Institutes of Health Stroke Scale (NIHSS) at End of Infusion Period, Months 3, 6 and 12(Baseline and End of Infusion and Months 3, 6 and 12)
- EuroQol EQ-5D (EQ-5D) at Month 6(Month 6)
- EuroQol EQ-5D (EQ-5D) at Month 12(Month 12)