Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1132-3434 | Registry Identifier | WHO |
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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.
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Actovegin | Active Comparator | 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. |
|
| Placebo | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Actovegin | Drug | Actovegin solution for infusion and Actovegin tablets |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline and Month 6 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Main Inclusion Criteria:
Main Exclusion Criteria:
Randomisation Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nycomed Investigational Site | Grodno | Belarus | ||||
| Nycomed Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28432265 | Derived | 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. |
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Participants who had suffered ischaemic stroke were enrolled equally in 1 of 2 treatment groups, actovegin 2000 mg solution (up to 20 infusions) followed by 200 mg tablets 3 times a day or placebo.
Participants took part in the study at 33 investigative sites in Belarus, Kazakhstan and Russia from 28 June 2012 to 26 November 2014.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Intent-to-treat population, all enrolled participants who received at least one dose of study drug, with data available for analysis. Missing individual item scores (where only some item scores missing) imputed with worst possible score and missing total scores (where all item scores missing) imputed by last observation carried forward. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline and Month 6 |
First dose of study drug to 10 days after last dose of study drug (up to approximately 6.5 months).
Any adverse events and abnormal laboratory findings irrespective of the relation to study treatment were documented. Safety population included all participants who received at least 1 dose of study drug based on treatment received. 2 participants in the placebo arm received actovegin and are included in the actovegin arm for safety analyses.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ischaemic stroke | Nervous system disorders | MedDRA 17.1 | Systematic Assessment | One treatment-emergent death occurred during treatment with actovegin and is not related and two treatment-emergent deaths occurred during treatment with placebo (1 of which also had Brain oedema and Hypostatic pneumonia) and are not related. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | MedDRA 17.1 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director, Clinical Science | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
Not provided
| ID | Term |
|---|---|
| D020521 | Stroke |
| D003072 | Cognition Disorders |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C015646 | Actovegin |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo |
| Drug |
Actovegin placebo-matching solution for infusion and Actovegin placebo-matching tablets |
|
| Baseline and Months 3 and 12 |
| 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. | Baseline, End of Infusion and Months 3, 6 and 12 |
| 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. | Baseline and Months 3, 6 and 12 |
| 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. | Month 6 |
| 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. | Baseline and End of Infusion and Months 3, 6 and 12 |
| 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. | Months 3 and 6 |
| 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. | Month 6 |
| 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. | Month 12 |
| 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). | Months 6 and 12 |
| 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:
| Months 3, 6 and 12 |
| 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]. | Month 6 and 12 |
| Minsk |
| Belarus |
| Nycomed Investigational Site | Vitebsk | Belarus |
| Nycomed Investigational Site | Almaty | Kazakhstan |
| Nycomed Investigational Site | Barnaul | Russia |
| Nycomed Investigational Site | Irkutsk | Russia |
| Nycomed Investigational Site | Kazan' | Russia |
| Nycomed Investigational Site | Krasnoyarsk | Russia |
| Nycomed Investigational Site | Moscow | Russia |
| Nycomed Investigational Site | Novosibirsk | Russia |
| Nycomed Investigational Site | Saint Petersburg | Russia |
| Nycomed Investigational Site | Samara | Russia |
| Nycomed Investigational Site | Tomsk | Russia |
| Nycomed Investigational Site | Yekaterinburg | Russia |
| Withdrawal by Participant |
|
| Lost to Follow-up |
|
| Physician Decision |
|
| Recurrent Stroke |
|
| Disallowed Concomitant Medication |
|
| Carotid or Neurosurgery |
|
| General Anaesthesia |
|
| Other Miscellaneous Reason |
|
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.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Age, Customized | Number | participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Region of Enrollment | Number | participants |
|
| Height | Mean | Standard Deviation | cm |
|
| Weight | Mean | Standard Deviation | kg |
|
| Number of Years of Education | Mean | Standard Deviation | years |
|
| Diabetes | Number | participants |
|
| Ischaemic Heart Disease or Peripheral Artery Disease | Number | participants |
|
| Previous Ischaemic Stroke | Number | participants |
|
| Smoking Status | Number | participants |
|
| Alcohol Consumption | Number | participants |
|
| Fertility Status of Female Participants | Female participants with available fertility status data only: 120 and 142 participants in each treatment arm, respectively. | Number | participants |
|
|
|
|
|
| Secondary | 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. | Intent-to-treat population, all enrolled participants who received at least one dose of study drug, with data available for analysis. Missing individual item scores (where only some item scores missing) imputed with worst possible score. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline and Months 3 and 12 |
|
|
|
|
| Secondary | 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. | Participants from the Intent-to-treat population, all enrolled participants who received at least one dose of study drug, with data available for analyses at the given time-point. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline, End of Infusion and Months 3, 6 and 12 |
|
|
|
|
| Secondary | 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. | Participants from the Intent-to-treat population, all enrolled participants who received at least one dose of study drug, with data available for analyses at the given time-point. | Posted | Number | percentage of responders | Baseline and Months 3, 6 and 12 |
|
|
|
|
| Secondary | 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. | Participants from the Intent-to-treat population, all enrolled participants who received at least one dose of study drug, with data available for analyses at the given time-point. | Posted | Number | percentage of participants | Month 6 |
|
|
|
|
| Secondary | 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. | Participants from the Intent-to-treat population, all enrolled participants who received at least one dose of study drug, with data available for analyses at the given time-point. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline and End of Infusion and Months 3, 6 and 12 |
|
|
|
|
| Secondary | 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. | Participants from the Intent-to-treat population, all enrolled participants who received at least one dose of study drug, with data available for analyses at the given time-point. | Posted | Median | Full Range | score on a scale | Months 3 and 6 |
|
|
|
| Secondary | 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. | Participants from the Intent-to-treat population, all enrolled participants who received at least one dose of study drug, with data available for analyses at the given time-point. | Posted | Number | percentage of participants | Month 6 |
|
|
|
| Secondary | 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. | Participants from the Intent-to-treat population, all enrolled participants who received at least one dose of study drug, with data available for analyses at the given time-point. | Posted | Number | percentage of participants | Month 12 |
|
|
|
| Secondary | 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). | Participants from the Intent-to-treat population, all enrolled participants who received at least one dose of study drug, with data available for analyses at the given time-point. | Posted | Mean | Standard Deviation | score on a scale | Months 6 and 12 |
|
|
|
| Secondary | 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:
| Participants from the Intent-to-treat population, all enrolled participants who received at least one dose of study drug, with data available for analyses at the given time-point. | Posted | Mean | Standard Deviation | score on a scale | Months 3, 6 and 12 |
|
|
|
| Secondary | 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]. | Participants from the Intent-to-treat population, all enrolled participants who received at least one dose of study drug, with data available for analyses at the given time-point. | Posted | Number | percentage of participants | Month 6 and 12 |
|
|
|
| 22 |
| 250 |
| 31 |
| 250 |
| EG001 | 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. | 17 | 253 | 31 | 253 |
|
| Brain oedema | Nervous system disorders | MedDRA 17.1 | Systematic Assessment | One treatment-emergent death occurred during treatment with actovegin and is not related and two treatment-emergent deaths occurred during treatment with placebo (1 participant also had Ischaemic stroke and Hypostatic pneumonia) and are not related. |
|
| Cerebral haemorrhage | Nervous system disorders | MedDRA 17.1 | Systematic Assessment | One treatment-emergent death occurred during treatment with actovegin and is not related. |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| VIIth Nerve Paralysis | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Myocardial infarction | Cardiac disorders | MedDRA 17.1 | Systematic Assessment | One treatment-emergent death occurred during treatment with actovegin and is not related. |
|
| Acute myocardial infarction | Cardiac disorders | MedDRA 17.1 | Systematic Assessment |
|
| Angina unstable | Cardiac disorders | MedDRA 17.1 | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA 17.1 | Systematic Assessment |
|
| Cardiopulmonary failure | Cardiac disorders | MedDRA 17.1 | Systematic Assessment | One treatment-emergent death occurred during treatment with actovegin and is not related. |
|
| Coronary artery disease | Cardiac disorders | MedDRA 17.1 | Systematic Assessment |
|
| Ischaemic cardiomyopathy | Cardiac disorders | MedDRA 17.1 | Systematic Assessment |
|
| Ventricular fibrillation | Cardiac disorders | MedDRA 17.1 | Systematic Assessment |
|
| Diverticulum intestinal | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Gastritis erosive | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Proctitis | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Astrocytoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 17.1 | Systematic Assessment |
|
| Metastases to liver | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 17.1 | Systematic Assessment |
|
| Pancreatic carcinoma metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 17.1 | Systematic Assessment |
|
| Endocarditis bacterial | Infections and infestations | MedDRA 17.1 | Systematic Assessment | One treatment-emergent death occurred during treatment with placebo and is not related. |
|
| Pneumonia | Infections and infestations | MedDRA 17.1 | Systematic Assessment | One treatment-emergent death occurred during treatment with actovegin and is not related. |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment | Two treatment-emergent deaths occurred during treatment with actovegin and are not related. |
|
| Arteriosclerosis | Vascular disorders | MedDRA 17.1 | Systematic Assessment | One treatment-emergent death occurred during treatment with placebo and is not related. |
|
| Hypertensive crisis | Vascular disorders | MedDRA 17.1 | Systematic Assessment |
|
| Death | General disorders | MedDRA 17.1 | Systematic Assessment | One treatment-emergent death occurred during treatment with placebo and is not related. No specific cause of death was identified or reported by the investigator. |
|
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Calculus urinary | Renal and urinary disorders | MedDRA 17.1 | Systematic Assessment |
|
| Respiratory tract infection viral | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Dyslipidaemia | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Amnesia | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Dementia | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 17.1 | Systematic Assessment |
|
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| <0.001 |
| LS Mean Difference |
| -3.7 |
| Standard Error of the Mean |
| 0.93 |
| 2-Sided |
| 95 |
| -5.5 |
| -1.9 |
| No |
| Superiority or Other |
| Change from Baseline at Month 6 (n=217, 228) |
|
| Change from Baseline at Month 12 (n=211, 220) |
|
| 0.016 |
| LS Mean Difference |
| 0.7 |
| Standard Error of the Mean |
| 0.27 |
| 2-Sided |
| 95 |
| 0.1 |
| 1.2 |
| No |
| Superiority or Other |
| Month 6 | ANCOVA | 0.013 | LS Mean Difference | 0.7 | Standard Error of the Mean | 0.29 | 2-Sided | 95 | 0.2 | 1.3 | No | Superiority or Other |
| Month 12 | ANCOVA | 0.003 | LS Mean Difference | 1.0 | Standard Error of the Mean | 0.34 | 2-Sided | 95 | 0.3 | 1.7 | No | Superiority or Other |
| Month 12 (n=200, 207) |
|
| 0.034 |
| Percent Difference |
| 10.2 |
| 2-Sided |
| 95 |
| 0.8 |
| 19.5 |
| No |
| Superiority or Other |
| Month 12 | Chi-squared | 0.035 | Percent Difference | 10.1 | 2-Sided | 95 | 0.8 | 19.3 | No | Superiority or Other |
| 0.221 |
| Percent Difference |
| -4.0 |
| 2-Sided |
| 95 |
| -9.7 |
| 1.7 |
| No |
| Superiority or Other |
| Change from Baseline at Month 6 (n=219, 228) |
|
| Change from Baseline at Month 12 (n=211, 220) |
|
| 0.136 |
| LS Mean Difference |
| -0.2 |
| Standard Error of the Mean |
| 0.14 |
| 2-Sided |
| 95 |
| -0.5 |
| 0.1 |
| No |
| Superiority or Other |
| Month 6 | ANCOVA | 0.890 | LS Mean Difference | 0.0 | Standard Error of the Mean | 0.14 | 2-Sided | 95 | -0.3 | 0.2 | No | Superiority or Other |
| Month 12 | ANCOVA | 0.455 | LS Mean Difference | -0.1 | Standard Error of the Mean | 0.14 | 2-Sided | 95 | -0.4 | 0.2 | No | Superiority or Other |
| Mobility_Moderate problem |
|
| Mobility_Severe problem |
|
| Mobility_Unable |
|
| Self-care_No problem |
|
| Self-care_Slight problem |
|
| Self-care_Moderate problem |
|
| Self-care_Severe problem |
|
| Self-care_Unable |
|
| Usual activities_No problem |
|
| Usual activities_Slight problem |
|
| Usual activities_Moderate problem |
|
| Usual activities_Severe problem |
|
| Usual activities_Unable |
|
| Pain or discomfort_No pain |
|
| Pain or discomfort_Slight pain |
|
| Pain or discomfort_Moderate pain |
|
| Pain or discomfort_Severe pain |
|
| Pain or discomfort_Extreme pain |
|
| Anxiety or depression_Not anxious |
|
| Anxiety or depression_Slightly anxious |
|
| Anxiety or depression_Moderately anxious |
|
| Anxiety or depression_Severely anxious |
|
| Anxiety or depression_Extremely anxious |
|
| Mobility_Moderate problem |
|
| Mobility_Severe problem |
|
| Mobility_Unable |
|
| Self-care_No problem |
|
| Self-care_Slight problem |
|
| Self-care_Moderate problem |
|
| Self-care_Severe problem |
|
| Self-care_Unable |
|
| Usual activities_No problem |
|
| Usual activities_Slight problem |
|
| Usual activities_Moderate problem |
|
| Usual activities_Severe problem |
|
| Usual activities_Unable |
|
| Pain or discomfort_No pain |
|
| Pain or discomfort_Slight pain |
|
| Pain or discomfort_Moderate pain |
|
| Pain or discomfort_Severe pain |
|
| Pain or discomfort_Extreme pain |
|
| Anxiety or depression_Not anxious |
|
| Anxiety or depression_Slightly anxious |
|
| Anxiety or depression_Moderately anxious |
|
| Anxiety or depression_Severely anxious |
|
| Anxiety or depression_Extremely anxious |
|
| Month 12 (n=212, 220) |
|