A Study on the Use of Tanakan® for Recovery of Neurological Impairment Following Ischaemic Stroke

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effectiveness of Tanakan® 240mg in association with Acetylsalicylic acid (325mg/day) in the recovery of neurological impairment following ischemic stroke.

Official Title
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A Phase III, Multicentre, Randomised, Double-blinded, Parallel Group, Placebo Controlled Clinical Study for Evaluating the Efficacy of EGb 761® (Tanakan®) (240mg) in the Recovery of Neurological Impairment Following Ischemic Stroke

Conditions
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Stroke, Acute, Neurological Impairment

Intervention / Treatment
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* Drug: EGb761
* Drug: Placebo
* Drug: Acetylsalicylic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient having had a single infarct in the carotid artery territory 3 to 8 days before inclusion Patient with a moderately severe or severe disability (Modified Rankin Score 4 or 5) Patient having a Quick's Test (for INR) and APPT (activated partial prothrombin time) test in the normal values of the laboratory Exclusion Criteria: Patients having had an ischemic stroke (CT confirmed) less than 3 days and more than 8 days prior Patient with known pre-existent cerebral infarction Infarct damaged area bigger than 1/3 hemisphere Patient having a score below the cut-off point at Frenchay Aphasia Short Test

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EGb761®<br>EGb761® 240 milligrams (mg)/day for 6 months administered orally, in association with acetylsalicylic acid (325 mg/day). The test treatment consists of 6 tablets/day. 2 tablets (each containing 40 mg EGb761®) taken orally with half a glass of water during 3 main meals. 1 tablet/day of acetylsalicylic acid during lunch. | Drug: EGb761<br>* EGb761 (Tanakan) 40 mg tablets (2 tablets t.i.d. (3 times a day)) 240 mg/day for 6 months.<br>* Other names: Tanakan;Drug: Acetylsalicylic acid<br>* Acetylsalicylic acid 325 mg/day (1 tablet once daily), for 6 months.<br>|
| Placebo Comparator: Placebo<br>6 months, administered orally, in association with acetylsalicylic acid (325 mg/day). The placebo consists of 6 tablets/day. 2 tablets taken orally with half a glass of water during 3 main meals. 1 tablet/day of acetylsalicylic acid during lunch. | Drug: Placebo<br>* Placebo 40 mg tablets (2 tablets t.i.d.) 240 mg/day for 6 months.<br>Drug: Acetylsalicylic acid<br>* Acetylsalicylic acid 325 mg/day (1 tablet once daily), for 6 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Modified Rankin Score of Less Than 3 at the End of Study Period. | The degree of disability and dependence in daily activities was assessed using the modified Rankin scale. The modified Rankin scale is a 6-point numerical scale (0=no symptoms at all, 1=no significant disability, 2=slight disability, 3=moderate disability, 4=moderately severe disability, 5=severe disability) which measures the degree of disability or dependence in the daily activities of people who have suffered a stroke. Assessments were made at baseline (Day 0) and at each follow-up visit on Day 28, Day 84 and Day 168. The percentage of subjects having a modified Rankin Score<3 at the end of the study (Day 168) are reported. | Day 168 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Modified Rankin Score of Less Than 3 at Day 28 and Day 84. | The degree of disability and dependence in daily activities was assessed using the modified Rankin scale. The modified Rankin scale is a 6-point numerical scale (0=no symptoms at all, 1=no significant disability, 2=slight disability, 3=moderate disability, 4=moderately severe disability, 5=severe disability) which measures the degree of disability or dependence in the daily activities of people who have suffered a stroke. Assessments were made at baseline (Day 0) and at each follow-up visit on Day 28, Day 84 and Day 168. The percentage of subjects having a modified Rankin Score<3 at each follow-up visit (not including end of study) are reported. | Up to Day 84 | 
| Percentage of Subjects at Each Point on the Modified Rankin Scale at Baseline, Day 28, Day 84 and Day 168. | The degree of disability and dependence in daily activities was assessed using the modified Rankin scale.The modified Rankin scale is a 6-point numerical scale (0=no symptoms at all, 1=no significant disability, 2=slight disability,3=moderate disability, 4=moderately severe disability, 5=severe disability) which measures the degree of disability or dependence in the daily activities of people who have suffered a stroke. Assessments were made at baseline (Day 0) and at each follow-up visit on Day 28, Day 84 and Day 168. The distribution of subjects according to disability severity scores was assessed and the percentage of subjects at each point on the modified Rankin scale are reported for each time point. | Up to Day 168 | 
| Mean Change From Baseline in Sandoz Clinical Assessment-Geriatric (SCAG) Scores at Day 28, Day 84 and Day 168. | The SCAG scale was to be used to evaluate the psychopathological state of the subject. It is composed of 18 symptom areas and an overall global assessment, all rated on a 7-point format from 1=not present to 7=severe. The total score range is from 19 to 133 (best to worst), with a negative mean change from baseline indicating an improvement in symptoms. Assessments were made at baseline (Day 0) and at each follow-up visit on Day 28, Day 84 and Day 168 and the mean change from baseline at each time point is reported. | Up to Day 168 | 
| Mean Change From Baseline in Barthel Index Scores at Day 28, Day 84 and Day 168. | The performance in activities of daily living was assessed by using the Barthel scale. The Barthel scale is an ordinal scale which measures 10 performance items describing activities of daily living. Each item is rated with a given number of points from 0 indicating total dependence up to a maximum of 10 or 15 (depending on performance item) indicating complete independence. The total score range is from 0 to 100 (worst to best), with a positive mean change indicating an improvement in independence. Assessments were made at baseline (Day 0) and at each follow-up visit on Day 28, Day 84 and Day 168 and the mean change from baseline at each time point is reported. | Up to Day 168 | 
| Mean Change From Baseline in the Mini Mental State (MMS) Test Scores at Day 28, Day 84 and Day 168. | The MMS test was used to evaluate the cognitive function of the subject. It includes tests of orientation, attention, memory, language and visual spatial skills, which are rated with a given number of points assigned to each level or ranking. The lower the score, the more important the mental deficit. The total score range is from 0 to 30 (worst to best), with a positive mean change indicating an improvement (i.e. less mental deficit). Assessments were made at baseline (Day 0) and at each follow-up visit on Day 28, Day 84 and Day 168 and the mean change from baseline at each time point is reported. | Up to Day 168 | 
| Mean Change From Baseline in the National Institute of Health Stroke Scale (NIHSS) Subscore for Questions 1a,1b and 1c at Day 28, Day 84 and Day 168. | The NIHSS was to be used to objectively quantify the impairment caused by the stroke.The NIHSS is composed of 11 items, each of which score a specific ability between 0 (normal function) and 4 (high level of impairment).The minimum total score is 0 and maximum is 42. Only 8 of the NIHSS subscores were calculated for this study. Assessments were made at baseline (Day 0) and at each follow-up visit on Day 28, Day 84 and Day 168. Mean NIHSS subscores for questions 1a (level of consciousness),1b (asking patient the month and their age), and 1c (asking to open and close eyes) were analysed using descriptive quantitative statistics at each visit and the mean change from baseline at each time point is reported. The range for the subscore for items 1a is 0 - 3, for 1b is 0 - 2 and for 1c is 0 - 2 (best to worst), with a negative mean change from baseline indicating an improvement. | Up to Day 168 |