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

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

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.

Study Overview

• Status: Completed
• Conditions: Stroke, Acute; Neurological Impairment
• Intervention / Treatment: Drug: EGb761; Drug: Acetylsalicylic acid; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 204
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Hradec Kralove, Czechia, 500 02
    • Faculty of Medicine in Hradec Kralove
  • Prague 2, Czechia, 120 00
    • General Faculty Hospital
• Poland
  • Katowice, Poland, 40 752
    • Department and Clinic of Neurology of the Old Age
  • Krakov, Poland, 31503
    • CMUJ Krakov
  • Warsaw, Poland, 00 416
    • Postgraduate Medical Teaching Center
• Romania
  • Bucharest, Romania, 75622
    • Institul de Boli Cerebro Vascular
  • Bucharest, Romania, Sector 5
    • Spitalul Universitar de Urgenţă
• Russian Federation
  • Moscow, Russian Federation, 117415
    • Russian State Medical University - Neurology and Neurosurgery Clinic
  • Moscow, Russian Federation, 129327
    • Russian State Medical University - Dept Fundamental Neurology & Neurosurgery
  • Yekaterinburg, Russian Federation, 620102
    • Ural State Medical Academy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EGb761®; 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; EGb761 (Tanakan) 40 mg tablets (2 tablets t.i.d. (3 times a day)) 240 mg/day for 6 months.; Other Names: Tanakan; Drug: Acetylsalicylic acid; Acetylsalicylic acid 325 mg/day (1 tablet once daily), for 6 months.
Placebo Comparator: Placebo; 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: Acetylsalicylic acid; Acetylsalicylic acid 325 mg/day (1 tablet once daily), for 6 months.; Drug: Placebo; Placebo 40 mg tablets (2 tablets t.i.d.) 240 mg/day for 6 months.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ipsen

Study record dates

Study Major Dates

• Study Start: February 1, 2003
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: January 12, 2006
• First Submitted That Met QC Criteria: January 12, 2006
• First Posted (Estimate): January 13, 2006

Study Record Updates

• Last Update Posted (Actual): January 8, 2019
• Last Update Submitted That Met QC Criteria: January 4, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: A-38-00240-704

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO