Trial Outcomes & Findings for Efficacy and Safety of Actovegin in Post-stroke Cognitive Impairment (PSCI) (NCT NCT01582854)
NCT ID: NCT01582854
Last Updated: 2016-02-22
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
503 participants
Primary outcome timeframe
Baseline and Month 6
Results posted on
2016-02-22
Participant Flow
Participants took part in the study at 33 investigative sites in Belarus, Kazakhstan and Russia from 28 June 2012 to 26 November 2014.
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.
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
248
|
255
|
|
Overall Study
COMPLETED
|
212
|
221
|
|
Overall Study
NOT COMPLETED
|
36
|
34
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
Death
|
8
|
5
|
|
Overall Study
Adverse Event
|
2
|
3
|
|
Overall Study
Withdrawal by Participant
|
8
|
11
|
|
Overall Study
Lost to Follow-up
|
1
|
2
|
|
Overall Study
Physician Decision
|
0
|
1
|
|
Overall Study
Recurrent Stroke
|
13
|
8
|
|
Overall Study
Disallowed Concomitant Medication
|
3
|
2
|
|
Overall Study
Carotid or Neurosurgery
|
0
|
1
|
|
Overall Study
General Anaesthesia
|
0
|
1
|
|
Overall Study
Other Miscellaneous Reason
|
1
|
0
|
Baseline Characteristics
Efficacy and Safety of Actovegin in Post-stroke Cognitive Impairment (PSCI)
Baseline characteristics by cohort
| Measure |
Actovegin
n=248 Participants
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
n=255 Participants
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.
|
Total
n=503 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
70.3 years
STANDARD_DEVIATION 6.65 • n=99 Participants
|
69.6 years
STANDARD_DEVIATION 7.18 • n=107 Participants
|
69.9 years
STANDARD_DEVIATION 6.92 • n=206 Participants
|
|
Age, Customized
≤ 65 years
|
78 participants
n=99 Participants
|
97 participants
n=107 Participants
|
175 participants
n=206 Participants
|
|
Age, Customized
> 65 years
|
170 participants
n=99 Participants
|
158 participants
n=107 Participants
|
328 participants
n=206 Participants
|
|
Sex: Female, Male
Female
|
120 Participants
n=99 Participants
|
142 Participants
n=107 Participants
|
262 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
128 Participants
n=99 Participants
|
113 Participants
n=107 Participants
|
241 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Asian
|
3 participants
n=99 Participants
|
3 participants
n=107 Participants
|
6 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
1 participants
n=99 Participants
|
1 participants
n=107 Participants
|
2 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
White
|
240 participants
n=99 Participants
|
248 participants
n=107 Participants
|
488 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Other
|
4 participants
n=99 Participants
|
3 participants
n=107 Participants
|
7 participants
n=206 Participants
|
|
Region of Enrollment
Russia
|
190 participants
n=99 Participants
|
195 participants
n=107 Participants
|
385 participants
n=206 Participants
|
|
Region of Enrollment
Kazakhstan
|
2 participants
n=99 Participants
|
2 participants
n=107 Participants
|
4 participants
n=206 Participants
|
|
Region of Enrollment
Belarus
|
56 participants
n=99 Participants
|
58 participants
n=107 Participants
|
114 participants
n=206 Participants
|
|
Height
|
167.6 cm
STANDARD_DEVIATION 7.47 • n=99 Participants
|
167.2 cm
STANDARD_DEVIATION 7.89 • n=107 Participants
|
167.4 cm
STANDARD_DEVIATION 7.68 • n=206 Participants
|
|
Weight
|
78.3 kg
STANDARD_DEVIATION 13.76 • n=99 Participants
|
78.0 kg
STANDARD_DEVIATION 13.73 • n=107 Participants
|
78.1 kg
STANDARD_DEVIATION 13.73 • n=206 Participants
|
|
Number of Years of Education
|
12.2 years
STANDARD_DEVIATION 3.41 • n=99 Participants
|
12.3 years
STANDARD_DEVIATION 3.40 • n=107 Participants
|
12.3 years
STANDARD_DEVIATION 3.40 • n=206 Participants
|
|
Diabetes
Yes
|
40 participants
n=99 Participants
|
57 participants
n=107 Participants
|
97 participants
n=206 Participants
|
|
Diabetes
No
|
208 participants
n=99 Participants
|
198 participants
n=107 Participants
|
406 participants
n=206 Participants
|
|
Ischaemic Heart Disease or Peripheral Artery Disease
Yes
|
245 participants
n=99 Participants
|
253 participants
n=107 Participants
|
498 participants
n=206 Participants
|
|
Ischaemic Heart Disease or Peripheral Artery Disease
No
|
3 participants
n=99 Participants
|
2 participants
n=107 Participants
|
5 participants
n=206 Participants
|
|
Previous Ischaemic Stroke
Yes
|
40 participants
n=99 Participants
|
38 participants
n=107 Participants
|
78 participants
n=206 Participants
|
|
Previous Ischaemic Stroke
No
|
208 participants
n=99 Participants
|
217 participants
n=107 Participants
|
425 participants
n=206 Participants
|
|
Smoking Status
Never smoked
|
172 participants
n=99 Participants
|
195 participants
n=107 Participants
|
367 participants
n=206 Participants
|
|
Smoking Status
Current smoker
|
53 participants
n=99 Participants
|
37 participants
n=107 Participants
|
90 participants
n=206 Participants
|
|
Smoking Status
Ex-smoker
|
23 participants
n=99 Participants
|
23 participants
n=107 Participants
|
46 participants
n=206 Participants
|
|
Alcohol Consumption
Never drank
|
117 participants
n=99 Participants
|
126 participants
n=107 Participants
|
243 participants
n=206 Participants
|
|
Alcohol Consumption
Occasional drinker
|
131 participants
n=99 Participants
|
128 participants
n=107 Participants
|
259 participants
n=206 Participants
|
|
Alcohol Consumption
Daily drinker
|
0 participants
n=99 Participants
|
1 participants
n=107 Participants
|
1 participants
n=206 Participants
|
|
Fertility Status of Female Participants
Surgically Sterile/Hysterectomized
|
3 participants
n=99 Participants
|
5 participants
n=107 Participants
|
8 participants
n=206 Participants
|
|
Fertility Status of Female Participants
Post-menopausal
|
117 participants
n=99 Participants
|
137 participants
n=107 Participants
|
254 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline and Month 6Population: 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.
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.
Outcome measures
| Measure |
Actovegin
n=224 Participants
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
n=234 Participants
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.
|
|---|---|---|
|
Change From Baseline in Alzheimer's Disease Assessment Scale + Cognitive Subscale Extended Version (ADAS-cog+) at Month 6
|
-6.8 score on a scale
Standard Error 0.58
|
-4.6 score on a scale
Standard Error 0.58
|
SECONDARY outcome
Timeframe: Baseline and Months 3 and 12Population: 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.
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.
Outcome measures
| Measure |
Actovegin
n=248 Participants
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
n=255 Participants
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.
|
|---|---|---|
|
Change From Baseline in ADAS-cog+ at Month 3 and Month 12
Change from Baseline at Month 3 (n=224, 234)
|
-5.4 score on a scale
Standard Error 0.53
|
-4.3 score on a scale
Standard Error 0.52
|
|
Change From Baseline in ADAS-cog+ at Month 3 and Month 12
Change from Baseline at Month 12 (n=211, 219)
|
-8.2 score on a scale
Standard Error 0.66
|
-4.5 score on a scale
Standard Error 0.66
|
SECONDARY outcome
Timeframe: Baseline, End of Infusion and Months 3, 6 and 12Population: 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.
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.
Outcome measures
| Measure |
Actovegin
n=248 Participants
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
n=255 Participants
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.
|
|---|---|---|
|
Change From Baseline in Montreal Cognitive Assessment Scale (MoCA) at End of Infusion Period, Months 3, 6 and 12
Change from BL at End of Infusion (n=242, 247)
|
2.1 score on a scale
Standard Error 0.15
|
1.8 score on a scale
Standard Error 0.15
|
|
Change From Baseline in Montreal Cognitive Assessment Scale (MoCA) at End of Infusion Period, Months 3, 6 and 12
Change from Baseline at Month 3 (n=224, 234)
|
3.4 score on a scale
Standard Error 0.20
|
2.7 score on a scale
Standard Error 0.20
|
|
Change From Baseline in Montreal Cognitive Assessment Scale (MoCA) at End of Infusion Period, Months 3, 6 and 12
Change from Baseline at Month 6 (n=217, 228)
|
3.8 score on a scale
Standard Error 0.21
|
3.1 score on a scale
Standard Error 0.21
|
|
Change From Baseline in Montreal Cognitive Assessment Scale (MoCA) at End of Infusion Period, Months 3, 6 and 12
Change from Baseline at Month 12 (n=211, 220)
|
3.9 score on a scale
Standard Error 0.25
|
2.9 score on a scale
Standard Error 0.24
|
SECONDARY outcome
Timeframe: Baseline and Months 3, 6 and 12Population: 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.
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.
Outcome measures
| Measure |
Actovegin
n=248 Participants
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
n=255 Participants
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.
|
|---|---|---|
|
Percentage of ADAS-cog+ Responders at Time Points 3, 6 and 12 Months
Month 3 (n=215, 223)
|
59.1 percentage of responders
|
48.9 percentage of responders
|
|
Percentage of ADAS-cog+ Responders at Time Points 3, 6 and 12 Months
Month 6 (n=208, 216)
|
62.5 percentage of responders
|
52.3 percentage of responders
|
|
Percentage of ADAS-cog+ Responders at Time Points 3, 6 and 12 Months
Month 12 (n=200, 207)
|
69.0 percentage of responders
|
58.9 percentage of responders
|
SECONDARY outcome
Timeframe: Month 6Population: 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.
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.
Outcome measures
| Measure |
Actovegin
n=218 Participants
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
n=228 Participants
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.
|
|---|---|---|
|
Percentage of Participants With a Diagnosis of Dementia
Month 6
|
7.3 percentage of participants
|
10.5 percentage of participants
|
|
Percentage of Participants With a Diagnosis of Dementia
Month 12
|
8.7 percentage of participants
|
12.7 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline and End of Infusion and Months 3, 6 and 12Population: 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.
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.
Outcome measures
| Measure |
Actovegin
n=248 Participants
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
n=255 Participants
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.
|
|---|---|---|
|
Change From Baseline in National Institutes of Health Stroke Scale (NIHSS) at End of Infusion Period, Months 3, 6 and 12
Change from BL at End of Infusion (n=243, 248)
|
-1.8 score on a scale
Standard Error 0.10
|
-1.7 score on a scale
Standard Error 0.10
|
|
Change From Baseline in National Institutes of Health Stroke Scale (NIHSS) at End of Infusion Period, Months 3, 6 and 12
Change from Baseline at Month 3 (n=224, 235)
|
-2.9 score on a scale
Standard Error 0.10
|
-2.7 score on a scale
Standard Error 0.10
|
|
Change From Baseline in National Institutes of Health Stroke Scale (NIHSS) at End of Infusion Period, Months 3, 6 and 12
Change from Baseline at Month 6 (n=219, 228)
|
-3.2 score on a scale
Standard Error 0.10
|
-3.2 score on a scale
Standard Error 0.10
|
|
Change From Baseline in National Institutes of Health Stroke Scale (NIHSS) at End of Infusion Period, Months 3, 6 and 12
Change from Baseline at Month 12 (n=211, 220)
|
-3.5 score on a scale
Standard Error 0.10
|
-3.4 score on a scale
Standard Error 0.10
|
SECONDARY outcome
Timeframe: Months 3 and 6Population: 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.
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.
Outcome measures
| Measure |
Actovegin
n=248 Participants
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
n=255 Participants
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.
|
|---|---|---|
|
Barthel Index at Months 3 and 6
Month 6 (n=219,228)
|
100.0 score on a scale
Interval 55.0 to 100.0
|
100.0 score on a scale
Interval 50.0 to 100.0
|
|
Barthel Index at Months 3 and 6
Month 3 (n=224,235)
|
100.0 score on a scale
Interval 55.0 to 100.0
|
100.0 score on a scale
Interval 9.0 to 100.0
|
SECONDARY outcome
Timeframe: Month 6Population: 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.
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.
Outcome measures
| Measure |
Actovegin
n=219 Participants
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
n=224 Participants
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.
|
|---|---|---|
|
EuroQol EQ-5D (EQ-5D) at Month 6
Mobility_No problem
|
41.5 percentage of participants
|
32.2 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 6
Mobility_Slight problem
|
29.8 percentage of participants
|
31.8 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 6
Mobility_Moderate problem
|
12.5 percentage of participants
|
16.5 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 6
Mobility_Severe problem
|
4.0 percentage of participants
|
7.1 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 6
Mobility_Unable
|
0.4 percentage of participants
|
0.4 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 6
Self-care_No problem
|
58.5 percentage of participants
|
48.6 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 6
Self-care_Slight problem
|
19.8 percentage of participants
|
25.5 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 6
Self-care_Moderate problem
|
7.7 percentage of participants
|
9.8 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 6
Self-care_Severe problem
|
2.0 percentage of participants
|
3.5 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 6
Self-care_Unable
|
0.4 percentage of participants
|
0.4 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 6
Usual activities_No problem
|
32.7 percentage of participants
|
32.9 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 6
Usual activities_Slight problem
|
40.7 percentage of participants
|
34.5 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 6
Usual activities_Moderate problem
|
8.9 percentage of participants
|
17.3 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 6
Usual activities_Severe problem
|
4.0 percentage of participants
|
2.5 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 6
Usual activities_Unable
|
2.0 percentage of participants
|
0.8 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 6
Pain or discomfort_No pain
|
50.0 percentage of participants
|
46.3 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 6
Pain or discomfort_Slight pain
|
30.6 percentage of participants
|
25.5 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 6
Pain or discomfort_Moderate pain
|
6.0 percentage of participants
|
15.3 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 6
Pain or discomfort_Severe pain
|
0.8 percentage of participants
|
0.8 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 6
Pain or discomfort_Extreme pain
|
0.4 percentage of participants
|
0 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 6
Anxiety or depression_Not anxious
|
50.0 percentage of participants
|
48.2 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 6
Anxiety or depression_Slightly anxious
|
31.0 percentage of participants
|
29.4 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 6
Anxiety or depression_Moderately anxious
|
6.0 percentage of participants
|
9.4 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 6
Anxiety or depression_Severely anxious
|
0.8 percentage of participants
|
0.8 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 6
Anxiety or depression_Extremely anxious
|
0.4 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Month 12Population: 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.
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.
Outcome measures
| Measure |
Actovegin
n=212 Participants
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
n=220 Participants
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.
|
|---|---|---|
|
EuroQol EQ-5D (EQ-5D) at Month 12
Anxiety or depression_Severely anxious
|
0.8 percentage of participants
|
0.8 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 12
Mobility_No problem
|
37.9 percentage of participants
|
36.5 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 12
Mobility_Slight problem
|
31.0 percentage of participants
|
29.4 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 12
Mobility_Moderate problem
|
12.5 percentage of participants
|
11.8 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 12
Mobility_Severe problem
|
3.2 percentage of participants
|
7.5 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 12
Mobility_Unable
|
0.8 percentage of participants
|
0.8 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 12
Self-care_No problem
|
55.2 percentage of participants
|
48.2 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 12
Self-care_Slight problem
|
22.2 percentage of participants
|
23.5 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 12
Self-care_Moderate problem
|
6.0 percentage of participants
|
9.4 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 12
Self-care_Severe problem
|
1.6 percentage of participants
|
3.9 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 12
Self-care_Unable
|
0.4 percentage of participants
|
0.8 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 12
Usual activities_No problem
|
32.7 percentage of participants
|
31.0 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 12
Usual activities_Slight problem
|
39.1 percentage of participants
|
33.7 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 12
Usual activities_Moderate problem
|
9.7 percentage of participants
|
15.7 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 12
Usual activities_Severe problem
|
2.8 percentage of participants
|
4.3 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 12
Usual activities_Unable
|
1.2 percentage of participants
|
1.2 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 12
Pain or discomfort_No pain
|
46.8 percentage of participants
|
46.7 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 12
Pain or discomfort_Slight pain
|
28.6 percentage of participants
|
26.3 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 12
Pain or discomfort_Moderate pain
|
8.5 percentage of participants
|
11.4 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 12
Pain or discomfort_Severe pain
|
1.6 percentage of participants
|
1.2 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 12
Pain or discomfort_Extreme pain
|
0 percentage of participants
|
0.4 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 12
Anxiety or depression_Not anxious
|
48.4 percentage of participants
|
47.1 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 12
Anxiety or depression_Slightly anxious
|
31.5 percentage of participants
|
27.1 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 12
Anxiety or depression_Moderately anxious
|
4.8 percentage of participants
|
10.6 percentage of participants
|
|
EuroQol EQ-5D (EQ-5D) at Month 12
Anxiety or depression_Extremely anxious
|
0 percentage of participants
|
0.4 percentage of participants
|
SECONDARY outcome
Timeframe: Months 6 and 12Population: 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.
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).
Outcome measures
| Measure |
Actovegin
n=248 Participants
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
n=255 Participants
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.
|
|---|---|---|
|
EuroQol EQ-5D (EQ-5D) General Health at Months 6 and 12
Month 6 (n=219, 224)
|
67.3 score on a scale
Standard Deviation 16.04
|
65.0 score on a scale
Standard Deviation 16.82
|
|
EuroQol EQ-5D (EQ-5D) General Health at Months 6 and 12
Month 12 (n=212, 220)
|
67.8 score on a scale
Standard Deviation 15.87
|
65.6 score on a scale
Standard Deviation 17.51
|
SECONDARY outcome
Timeframe: Months 3, 6 and 12Population: 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.
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
Outcome measures
| Measure |
Actovegin
n=248 Participants
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
n=255 Participants
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.
|
|---|---|---|
|
Beck Depression Inventory, Version II (BDI-II) at Months 3, 6 and 12
Month 6 (n=219, 227)
|
11.3 score on a scale
Standard Deviation 8.88
|
11.5 score on a scale
Standard Deviation 10.58
|
|
Beck Depression Inventory, Version II (BDI-II) at Months 3, 6 and 12
Month 12 (n=212, 220)
|
10.7 score on a scale
Standard Deviation 7.10
|
11.5 score on a scale
Standard Deviation 8.24
|
|
Beck Depression Inventory, Version II (BDI-II) at Months 3, 6 and 12
Month 3 (n=224, 234)
|
12.5 score on a scale
Standard Deviation 11.02
|
11.6 score on a scale
Standard Deviation 8.08
|
SECONDARY outcome
Timeframe: Month 6 and 12Population: 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.
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) \[Classification of Mental and Behavioural Disorders, Diagnostic Criteria for Research\].
Outcome measures
| Measure |
Actovegin
n=248 Participants
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
n=255 Participants
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.
|
|---|---|---|
|
Percentage of Participants With a Diagnosis of Dementia
Month 6
|
7.3 percentage of participants
|
10.5 percentage of participants
|
|
Percentage of Participants With a Diagnosis of Dementia
Month 12
|
8.7 percentage of participants
|
12.7 percentage of participants
|
Adverse Events
Actovegin
Serious events: 22 serious events
Other events: 31 other events
Deaths: 0 deaths
Placebo
Serious events: 17 serious events
Other events: 31 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Actovegin
n=250 participants at risk
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
n=253 participants at risk
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.
|
|---|---|---|
|
Nervous system disorders
Ischaemic stroke
|
5.2%
13/250 • 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.
|
2.0%
5/253 • 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.
|
|
Nervous system disorders
Brain oedema
|
0.40%
1/250 • 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.
|
0.79%
2/253 • 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.
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.40%
1/250 • 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.
|
0.00%
0/253 • 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.
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/250 • 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.
|
0.40%
1/253 • 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.
|
|
Nervous system disorders
VIIth Nerve Paralysis
|
0.00%
0/250 • 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.
|
0.40%
1/253 • 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.
|
|
Cardiac disorders
Myocardial infarction
|
0.40%
1/250 • 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.
|
0.40%
1/253 • 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.
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/250 • 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.
|
0.40%
1/253 • 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.
|
|
Cardiac disorders
Angina unstable
|
0.00%
0/250 • 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.
|
0.40%
1/253 • 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.
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/250 • 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.
|
0.40%
1/253 • 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.
|
|
Cardiac disorders
Cardiopulmonary failure
|
0.40%
1/250 • 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.
|
0.00%
0/253 • 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.
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/250 • 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.
|
0.40%
1/253 • 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.
|
|
Cardiac disorders
Ischaemic cardiomyopathy
|
0.00%
0/250 • 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.
|
0.40%
1/253 • 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.
|
|
Cardiac disorders
Ventricular fibrillation
|
0.00%
0/250 • 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.
|
0.40%
1/253 • 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.
|
|
Gastrointestinal disorders
Diverticulum intestinal
|
0.00%
0/250 • 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.
|
0.40%
1/253 • 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.
|
|
Gastrointestinal disorders
Gastritis erosive
|
0.00%
0/250 • 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.
|
0.40%
1/253 • 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.
|
|
Gastrointestinal disorders
Proctitis
|
0.40%
1/250 • 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.
|
0.00%
0/253 • 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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Astrocytoma
|
0.00%
0/250 • 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.
|
0.40%
1/253 • 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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to liver
|
0.00%
0/250 • 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.
|
0.40%
1/253 • 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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma metastatic
|
0.00%
0/250 • 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.
|
0.40%
1/253 • 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.
|
|
Infections and infestations
Endocarditis bacterial
|
0.00%
0/250 • 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.
|
0.40%
1/253 • 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.
|
|
Infections and infestations
Pneumonia
|
0.40%
1/250 • 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.
|
0.00%
0/253 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.80%
2/250 • 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.
|
0.00%
0/253 • 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.
|
|
Vascular disorders
Arteriosclerosis
|
0.00%
0/250 • 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.
|
0.40%
1/253 • 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.
|
|
Vascular disorders
Hypertensive crisis
|
0.40%
1/250 • 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.
|
0.00%
0/253 • 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.
|
|
General disorders
Death
|
0.00%
0/250 • 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.
|
0.40%
1/253 • 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.
|
|
Metabolism and nutrition disorders
Type 2 diabetes mellitus
|
0.00%
0/250 • 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.
|
0.40%
1/253 • 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.
|
|
Renal and urinary disorders
Calculus urinary
|
0.40%
1/250 • 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.
|
0.00%
0/253 • 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.
|
Other adverse events
| Measure |
Actovegin
n=250 participants at risk
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
n=253 participants at risk
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.
|
|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
2.0%
5/250 • 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.
|
1.2%
3/253 • 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.
|
|
Infections and infestations
Respiratory tract infection viral
|
2.0%
5/250 • 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.
|
3.2%
8/253 • 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.
|
|
Metabolism and nutrition disorders
Dyslipidaemia
|
3.2%
8/250 • 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.
|
0.79%
2/253 • 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.
|
|
Nervous system disorders
Amnesia
|
0.00%
0/250 • 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.
|
2.8%
7/253 • 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.
|
|
Nervous system disorders
Dementia
|
2.0%
5/250 • 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.
|
3.6%
9/253 • 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.
|
|
Nervous system disorders
Headache
|
2.8%
7/250 • 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.
|
2.8%
7/253 • 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.
|
|
Vascular disorders
Hypertension
|
2.0%
5/250 • 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.
|
1.2%
3/253 • 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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER