Back to resultsEfficacy and Safety of Actovegin in Post-stroke Cognitive Impairment (PSCI) (ARTEMIDA)
Primary Purpose
Post-Stroke Cognitive Impairment (PSCI)
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Actovegin
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Post-Stroke Cognitive Impairment (PSCI) focused on measuring Post-Stroke Cognitive Impairment (PSCI), Stroke, Actovegin, Cognition disorders
Eligibility Criteria
Main 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).
Main 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.
Sites / Locations
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Actovegin
Placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Change From Baseline in Alzheimer's Disease Assessment Scale + Cognitive Subscale Extended Version (ADAS-cog+) at 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 Outcome Measures
Change From Baseline in ADAS-cog+ at Month 3 and Month 12
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.
Change From Baseline in Montreal Cognitive Assessment Scale (MoCA) at End of Infusion Period, Months 3, 6 and 12
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.
Percentage of ADAS-cog+ Responders at Time Points 3, 6 and 12 Months
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.
Percentage of Participants With a Diagnosis of Dementia
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.
Change From Baseline in National Institutes of Health Stroke Scale (NIHSS) at End of Infusion Period, Months 3, 6 and 12
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.
Barthel Index at Months 3 and 6
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.
EuroQol EQ-5D (EQ-5D) at Month 6
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.
EuroQol EQ-5D (EQ-5D) at Month 12
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.
EuroQol EQ-5D (EQ-5D) General Health at Months 6 and 12
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).
Beck Depression Inventory, Version II (BDI-II) at Months 3, 6 and 12
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
Percentage of Participants With a Diagnosis of Dementia
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].
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01582854
Brief Title
Efficacy and Safety of Actovegin in Post-stroke Cognitive Impairment (PSCI)
Acronym
ARTEMIDA
Official Title
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).
Study Type
Interventional
2. Study Status
Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
June 2012 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
November 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post-Stroke Cognitive Impairment (PSCI)
Keywords
Post-Stroke Cognitive Impairment (PSCI), Stroke, Actovegin, Cognition disorders
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
503 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Actovegin
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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 Type
Drug
Intervention Name(s)
Actovegin
Intervention Description
Actovegin solution for infusion and Actovegin tablets
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Actovegin placebo-matching solution for infusion and Actovegin placebo-matching tablets
Primary Outcome Measure Information:
Title
Change From Baseline in Alzheimer's Disease Assessment Scale + Cognitive Subscale Extended Version (ADAS-cog+) at Month 6
Description
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
Secondary Outcome Measure Information:
Title
Change From Baseline in ADAS-cog+ at Month 3 and Month 12
Description
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
Title
Change From Baseline in Montreal Cognitive Assessment Scale (MoCA) at End of Infusion Period, Months 3, 6 and 12
Description
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
Title
Percentage of ADAS-cog+ Responders at Time Points 3, 6 and 12 Months
Description
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
Title
Percentage of Participants With a Diagnosis of Dementia
Description
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
Title
Change From Baseline in National Institutes of Health Stroke Scale (NIHSS) at End of Infusion Period, Months 3, 6 and 12
Description
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
Title
Barthel Index at Months 3 and 6
Description
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
Title
EuroQol EQ-5D (EQ-5D) at Month 6
Description
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
Title
EuroQol EQ-5D (EQ-5D) at Month 12
Description
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
Title
EuroQol EQ-5D (EQ-5D) General Health at Months 6 and 12
Description
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
Title
Beck Depression Inventory, Version II (BDI-II) at Months 3, 6 and 12
Description
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
Title
Percentage of Participants With a Diagnosis of Dementia
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Main 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).
Main 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.
Facility Information:
Facility Name
Nycomed Investigational Site
City
Grodno
Country
Belarus
Facility Name
Nycomed Investigational Site
City
Minsk
Country
Belarus
Facility Name
Nycomed Investigational Site
City
Vitebsk
Country
Belarus
Facility Name
Nycomed Investigational Site
City
Almaty
Country
Kazakhstan
Facility Name
Nycomed Investigational Site
City
Barnaul
Country
Russian Federation
Facility Name
Nycomed Investigational Site
City
Ekaterinburg
Country
Russian Federation
Facility Name
Nycomed Investigational Site
City
Irkutsk
Country
Russian Federation
Facility Name
Nycomed Investigational Site
City
Kazan
Country
Russian Federation
Facility Name
Nycomed Investigational Site
City
Krasnoyarsk
Country
Russian Federation
Facility Name
Nycomed Investigational Site
City
Moscow
Country
Russian Federation
Facility Name
Nycomed Investigational Site
City
Novosibirsk
Country
Russian Federation
Facility Name
Nycomed Investigational Site
City
Samara
Country
Russian Federation
Facility Name
Nycomed Investigational Site
City
St. Petersburg
Country
Russian Federation
Facility Name
Nycomed Investigational Site
City
Tomsk
Country
Russian Federation
12. IPD Sharing Statement
Citations:
PubMed Identifier
28432265
Citation
Guekht A, Skoog I, Edmundson S, Zakharov V, Korczyn AD. ARTEMIDA Trial (A Randomized Trial of Efficacy, 12 Months International Double-Blind Actovegin): A Randomized Controlled Trial to Assess the Efficacy of Actovegin in Poststroke Cognitive Impairment. Stroke. 2017 May;48(5):1262-1270. doi: 10.1161/STROKEAHA.116.014321.
Results Reference
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Efficacy and Safety of Actovegin in Post-stroke Cognitive Impairment (PSCI)
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