Clinical trial NCT01582854: Efficacy and Safety of Actovegin in Post-stroke Cognitive Impairment (PSCI)
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Post-Stroke Cognitive Impairment (PSCI)
Keywords: Post-Stroke Cognitive Impairment (PSCI)
Stroke
Actovegin
Cognition disorders
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2012-04-23
Enrollment: 503
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change From Baseline in Alzheimer's Disease Assessment Scale + Cognitive Subscale Extended Version (ADAS-cog+) at Month 6
timeFrame: Baseline and Month 6
Secondary outcomes:
measure: Change From Baseline in ADAS-cog+ at Month 3 and Month 12
timeFrame: Baseline and Months 3 and 12
measure: Change From Baseline in Montreal Cognitive Assessment Scale (MoCA) at End of Infusion Period, Months 3, 6 and 12
timeFrame: Baseline, End of Infusion and Months 3, 6 and 12
measure: Percentage of ADAS-cog+ Responders at Time Points 3, 6 and 12 Months
timeFrame: Baseline and Months 3, 6 and 12
measure: Percentage of Participants With a Diagnosis of Dementia
timeFrame: Month 6
measure: Change From Baseline in National Institutes of Health Stroke Scale (NIHSS) at End of Infusion Period, Months 3, 6 and 12
timeFrame: Baseline and End of Infusion and Months 3, 6 and 12
measure: Barthel Index at Months 3 and 6
timeFrame: Months 3 and 6
measure: EuroQol EQ-5D (EQ-5D) at Month 6
timeFrame: Month 6
measure: EuroQol EQ-5D (EQ-5D) at Month 12
timeFrame: Month 12
measure: EuroQol EQ-5D (EQ-5D) General Health at Months 6 and 12
timeFrame: Months 6 and 12
measure: Beck Depression Inventory, Version II (BDI-II) at Months 3, 6 and 12
timeFrame: Months 3, 6 and 12
measure: Percentage of Participants With a Diagnosis of Dementia
timeFrame: Month 6 and 12
Other outcomes:
Locations:
city: Grodno
country: Belarus
facility: Nycomed Investigational Site
city: Minsk
country: Belarus
facility: Nycomed Investigational Site
city: Vitebsk
country: Belarus
facility: Nycomed Investigational Site
city: Almaty
country: Kazakhstan
facility: Nycomed Investigational Site
city: Barnaul
country: Russian Federation
facility: Nycomed Investigational Site
city: Ekaterinburg
country: Russian Federation
facility: Nycomed Investigational Site
city: Irkutsk
country: Russian Federation
facility: Nycomed Investigational Site
city: Kazan
country: Russian Federation
facility: Nycomed Investigational Site
city: Krasnoyarsk
country: Russian Federation
facility: Nycomed Investigational Site
city: Moscow
country: Russian Federation
facility: Nycomed Investigational Site
city: Novosibirsk
country: Russian Federation
facility: Nycomed Investigational Site
city: Samara
country: Russian Federation
facility: Nycomed Investigational Site
city: St. Petersburg
country: Russian Federation
facility: Nycomed Investigational Site
city: Tomsk
country: Russian Federation
facility: Nycomed Investigational Site
Study officials:
References:
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.