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A Randomized, Clinical Trial of Vitamin E and Memantine in Alzheimer's Disease (TEAM-AD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00235716
Recruitment Status : Completed
First Posted : October 10, 2005
Results First Posted : January 29, 2014
Last Update Posted : July 23, 2014
Sponsor:
Collaborators:
Forest Laboratories
DSM Nutritional Products, Inc.
Information provided by (Responsible Party):
VA Office of Research and Development ( US Department of Veterans Affairs )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Factorial Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Alzheimer's Disease
Interventions Drug: dl-alpha-tocopherol
Drug: Memantine
Drug: Placebo
Enrollment 613
Recruitment Details Recruitment initiated in August, 2007 and concluded in March, 2012. Enrollment took place at 14 VA medical centers.
Pre-assignment Details  
Arm/Group Title Vitamin E Memantine (Namenda) Vitamin E + Memantine Placebo
Hide Arm/Group Description Alpha-tocopherol (vitamin E in the form of dl-alpha-tocopheryl acetate), 2000 international units (IU) per day, taken as one 1000 IU hard-gelatin, liquid-filled capsules twice a day plus matching memantine placebos. Memantine 20 mg per day, titrated over four weeks to a maintenance dosage of 10 mg pills taken twice a day plus matching vitamin E placebo. 2000 IU of Alpha-tocopherol (vitamin E) per day plus 20 mg memantine per day. Matching placebo pills for vitamin E and memantine
Period Title: Overall Study
Started 152 155 154 152
Completed 90 88 89 90
Not Completed 62 67 65 62
Reason Not Completed
Death             26             39             32             31
Withdrawal by Subject             23             19             17             18
Lost to Follow-up             12             7             14             10
Adverse Event             1             1             1             0
Physician Decision             0             1             1             3
Arm/Group Title Vitamin E Memantine (Namenda) Vitamin E + Memantine Placebo Total
Hide Arm/Group Description Alpha-tocopherol (vitamin E in the form of dl-alpha-tocopheryl acetate), 2000 international units (IU) per day, taken as one 1000 IU hard-gelatin, liquid-filled capsules twice a day plus matching memantine placebos. Memantine 20 mg per day, titrated over four weeks to a maintenance dosage of 10 mg pills taken twice a day plus matching vitamin E placebo. 2000 IU of Alpha-tocopherol (vitamin E) per day plus 20 mg memantine per day. Matching placebo pills for vitamin E and memantine Total of all reporting groups
Overall Number of Baseline Participants 152 155 154 152 613
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 152 participants 155 participants 154 participants 152 participants 613 participants
78.6  (7.2) 78.8  (7.2) 78.3  (7.0) 79.4  (7.0) 78.8  (7.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 152 participants 155 participants 154 participants 152 participants 613 participants
Female
6
   3.9%
6
   3.9%
4
   2.6%
3
   2.0%
19
   3.1%
Male
146
  96.1%
149
  96.1%
150
  97.4%
149
  98.0%
594
  96.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 152 participants 155 participants 154 participants 152 participants 613 participants
Hispanic or Latino
17
  11.2%
15
   9.7%
15
   9.7%
19
  12.5%
66
  10.8%
Not Hispanic or Latino
135
  88.8%
140
  90.3%
139
  90.3%
133
  87.5%
547
  89.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 152 participants 155 participants 154 participants 152 participants 613 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.7%
1
   0.2%
Asian
0
   0.0%
1
   0.6%
0
   0.0%
0
   0.0%
1
   0.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   0.6%
0
   0.0%
0
   0.0%
1
   0.2%
Black or African American
21
  13.8%
21
  13.5%
18
  11.7%
20
  13.2%
80
  13.1%
White
130
  85.5%
132
  85.2%
136
  88.3%
131
  86.2%
529
  86.3%
More than one race
1
   0.7%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 152 participants 155 participants 154 participants 152 participants 613 participants
152 155 154 152 613
Education  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 152 participants 155 participants 154 participants 152 participants 613 participants
<High School Graduation 41 41 26 29 137
High School Graduation 46 48 57 56 207
Some College 27 38 37 33 135
College Graduation or Advanced Degree 38 28 34 34 134
Apolipoprotein E ε4 status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 152 participants 155 participants 154 participants 152 participants 613 participants
Non-carriers 47 48 59 55 209
One ε4 allele 39 44 44 38 165
Two ε4 alleles 10 13 8 10 41
Not Tested 56 50 43 49 198
[1]
Measure Description: Data collected through genetic sub-study with separate informed consent.
Concomitant Medications Acetylcholinesterase Inhibitors (AChEI)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 152 participants 155 participants 154 participants 152 participants 613 participants
Donepezil 104 100 100 96 400
Galantamine 43 47 49 55 194
Rivastigmine 5 8 4 1 18
None 0 0 1 0 1
Weeks from AChEI Initiation to Randomization  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 152 participants 155 participants 154 participants 152 participants 613 participants
≤ 12 weeks 46 36 49 37 168
> 12 weeks 105 119 104 115 443
Missing 1 0 1 0 2
Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory  
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 152 participants 155 participants 154 participants 152 participants 613 participants
56.6  (14.9) 57.3  (14.2) 56.4  (14.0) 56.8  (13.7) 56.8  (14.2)
Mini-Mental State Examination  
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 152 participants 155 participants 154 participants 152 participants 613 participants
21.3  (3.3) 20.8  (3.8) 21.3  (3.4) 20.8  (3.8) 21.0  (3.6)
Alzheimer's Disease Assessment Scale - Cognitive portion  
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 152 participants 155 participants 154 participants 152 participants 613 participants
18.5  (8.8) 19.5  (7.9) 18.0  (8.4) 19.1  (8.4) 18.8  (8.4)
Neuropsychiatric Inventory  
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 152 participants 155 participants 154 participants 152 participants 613 participants
12.2  (13.3) 12.1  (13.1) 12.3  (13.3) 13.5  (14.2) 12.5  (13.4)
Caregiver Activity Survey  
Mean (Standard Deviation)
Unit of measure:  Hours per day
Number Analyzed 152 participants 155 participants 154 participants 152 participants 613 participants
7.3  (14.3) 6.7  (9.0) 6.6  (10.5) 6.5  (9.2) 6.8  (10.9)
Dependence Scale   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 152 participants 155 participants 154 participants 152 participants 613 participants
Level 0 5 6 8 3 22
Level 1 8 6 8 5 27
Level 2 85 91 80 79 335
Level 3 31 35 31 37 134
Level 4 4 7 10 8 29
Level 5 19 10 17 20 66
[1]
Measure Description: Higher the level the more dependence / less independence.
1.Primary Outcome
Title Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS/ADL) Inventory Change From Baseline
Time Frame 6, 12, 18, 24, 30, 36, 42 and 48 months minus baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat analysis that includes all participants with baseline and at least one follow-up measurement.
Arm/Group Title Vitamin E Memantine Vitamin E + Memantine Placebo
Hide Arm/Group Description:
Alpha-tocopherol (vitamin E in the form of dl-alpha-tocopheryl acetate), 2000 international units (IU) per day, taken as one 1000 IU hard-gelatin, liquid-filled capsules twice a day plus matching memantine placebos.
Memantine 20 mg per day, titrated over four weeks to a maintenance dosage of 10 mg pills taken twice a day plus matching vitamin E placebo.
2000 IU of Alpha-tocopherol (vitamin E) per day plus 20 mg memantine per day.
Matching placebo pills for vitamin E and memantine
Overall Number of Participants Analyzed 140 142 139 140
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
6 months minus baseline -1.72  (0.95) -2.40  (0.94) -2.78  (0.96) -4.52  (0.95)
12 months minus baseline -4.29  (1.20) -6.99  (1.21) -6.60  (1.21) -8.11  (1.23)
18 months minus baseline -8.01  (1.40) -9.32  (1.42) -7.98  (1.41) -10.21  (1.43)
24 months minus baseline -11.88  (1.66) -14.06  (1.70) -12.82  (1.68) -16.18  (1.74)
30 months minus baseline -15.84  (1.94) -18.30  (1.97) -15.66  (1.97) -19.67  (2.06)
36 months minus baseline -19.71  (2.34) -18.78  (2.43) -18.89  (2.32) -24.82  (2.51)
42 months minus baseline -25.30  (2.57) -23.48  (2.65) -23.44  (2.52) -28.13  (2.76)
48 months minus baseline -26.55  (3.11) -24.60  (3.18) -29.25  (3.08) -27.55  (3.38)
Average change from baseline -13.81  (1.11) -14.98  (1.10) -15.20  (1.11) -16.96  (1.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vitamin E, Placebo
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments p-value adjusted for 6 treatment group comparisons.
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.15
Confidence Interval (2-Sided) 95%
0.92 to 5.39
Estimation Comments Mean difference is the least squares mean changes from baseline for the vitamin E group minus the placebo group.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Memantine, Placebo
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.40
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.98
Confidence Interval (2-Sided) 95%
-0.24 to 4.20
Estimation Comments Mean difference is the least squares mean changes from baseline for the memantine group minus the placebo group.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Vitamin E + Memantine, Placebo
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.49
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.76
Confidence Interval (2-Sided) 95%
-0.48 to 4.00
Estimation Comments Mean difference is the least squares mean changes from baseline for the vitamin E + memantine group minus the placebo group.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Vitamin E, Vitamin E + Memantine
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.60
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.39
Confidence Interval (2-Sided) 95%
-3.63 to 0.85
Estimation Comments Mean difference is the least squares mean changes from baseline for the vitamin E + memantine group minus the vitamin E group.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Memantine, Vitamin E + Memantine
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.85
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.22
Confidence Interval (2-Sided) 95%
-2.44 to 2.01
Estimation Comments Mean difference is the least squares mean changes from baseline for the vitamin E + memantine group minus the memantine group.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Vitamin E, Memantine
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.60
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.18
Confidence Interval (2-Sided) 95%
-1.04 to 3.39
Estimation Comments Mean difference is the least squares mean changes from baseline for the vitamin E group minus the memantine group.
2.Primary Outcome
Title Mini-Mental State Examination Change From Baseline
Hide Description The Mini-Mental State Examination (MMSE) briefly and objectively assess cognitive status in psychiatric patients with cognitive impairment. The MMSE questions are grouped into seven categories, each representing a different cognitive domain. The MMSE yields a total score that ranges from 0 for a patient who gives no correct response to a score of 30 for a patient who makes no errors. Outcome analysis is average least square means change from baseline.
Time Frame 6, 12, 18, 24, 30, 36, 42 and 48 months minus baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat analysis that includes all participants with baseline and at least one follow-up measurement.
Arm/Group Title Vitamin E Memantine Vitamin E + Memantine Placebo
Hide Arm/Group Description:
Alpha-tocopherol (vitamin E in the form of dl-alpha-tocopheryl acetate), 2000 international units (IU) per day, taken as one 1000 IU hard-gelatin, liquid-filled capsules twice a day plus matching memantine placebos.
Memantine 20 mg per day, titrated over four weeks to a maintenance dosage of 10 mg pills taken twice a day plus matching vitamin E placebo.
2000 IU of Alpha-tocopherol (vitamin E) per day plus 20 mg memantine per day.
Matching placebo pills for vitamin E and memantine
Overall Number of Participants Analyzed 136 140 136 137
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
6 months minus baseline -0.35  (0.29) -0.24  (0.28) -0.20  (0.29) -0.34  (0.29)
12 months minus baseline -0.95  (0.34) -1.09  (0.34) -0.65  (0.34) -1.39  (0.35)
18 months minus baseline -2.00  (0.44) -2.62  (0.45) -1.22  (0.44) -2.21  (0.45)
24 months minus baseline -2.62  (0.52) -3.44  (0.54) -2.29  (0.53) -2.90  (0.55)
30 months minus baseline -3.67  (0.61) -3.79  (0.63) -3.16  (0.61) -3.26  (0.65)
36 months minus baseline -4.97  (0.74) -4.26  (0.78) -3.69  (0.73) -3.87  (0.79)
42 months minus baseline -4.84  (0.79) -4.59  (0.80) -3.80  (0.74) -4.68  (0.83)
48 months minus baseline -5.26  (0.94) -5.98  (0.98) -5.70  (0.91) -5.42  (1.02)
Average change from baseline -2.97  (0.33) -3.05  (0.33) -2.80  (0.33) -3.16  (0.33)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vitamin E, Placebo
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.84
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
-0.54 to 0.92
Estimation Comments Mean difference is the least squares mean changes from baseline for the vitamin E group minus the placebo group.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Memantine, Placebo
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.84
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.12
Confidence Interval (2-Sided) 95%
-0.61 to 0.84
Estimation Comments Mean difference is the least squares mean changes from baseline for the memantine group minus the placebo group.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Vitamin E + Memantine, Placebo
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.84
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.37
Confidence Interval (2-Sided) 95%
-0.36 to 1.10
Estimation Comments Mean difference is the least squares mean changes from baseline for the vitamin E + memantine group minus the placebo group.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Vitamin E, Vitamin E + Memantine
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.84
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.17
Confidence Interval 95%
-0.56 to 0.90
Estimation Comments Mean difference is the least squares mean changes from baseline for the vitamin E + memantine group minus the vitamin E group.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Memantine, Vitamin E + Memantine
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.84
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.25
Confidence Interval (2-Sided) 95%
-0.47 to 0.98
Estimation Comments Mean difference is the least squares mean changes from baseline for the vitamin E + memantine group minus the memantine group.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Vitamin E, Memantine
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.84
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
-0.65 to 0.80
Estimation Comments Mean difference is the least squares mean changes from baseline for the vitamin E group minus the memantine group.
3.Primary Outcome
Title Alzheimer's Disease Assessment Scale - Cognitive (ADAS-cog) Change From Baseline
Hide Description The Alzheimer's Disease Assessment Scale (ADAS) is a 21-item scale designed to assess the severity of cognitive and non-cognitive behavioral impairments in patients with Alzheimer's disease. The cognitive portion of the scale (ADAS-cog) consists of 11 items to assess memory, language, and praxis functions. The ADAS-cog total score ranges from 0 (no errors) to 70 (severe cognitive impairment). Outcome analysis is average least square means change from baseline.
Time Frame 6, 12, 18, 24, 30, 36, 42 and 48 months minus baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat analysis that includes all participants with baseline and at least one follow-up measurement.
Arm/Group Title Vitamin E Memantine Vitamin E + Memantine Placebo
Hide Arm/Group Description:
Alpha-tocopherol (vitamin E in the form of dl-alpha-tocopheryl acetate), 2000 international units (IU) per day, taken as one 1000 IU hard-gelatin, liquid-filled capsules twice a day plus matching memantine placebos.
Memantine 20 mg per day, titrated over four weeks to a maintenance dosage of 10 mg pills taken twice a day plus matching vitamin E placebo.
2000 IU of Alpha-tocopherol (vitamin E) per day plus 20 mg memantine per day.
Matching placebo pills for vitamin E and memantine
Overall Number of Participants Analyzed 135 140 136 137
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
6 months minus baseline 1.38  (0.63) 1.11  (0.62) 1.53  (0.63) 3.04  (0.63)
12 months minus baseline 2.40  (0.72) 3.32  (0.72) 2.48  (0.72) 4.26  (0.74)
18 months minus baseline 4.34  (0.91) 5.69  (0.91) 3.46  (0.90) 6.04  (0.92)
24 months minus baseline 4.32  (1.10) 6.73  (1.12) 5.76  (1.11) 6.71  (1.15)
30 months minus baseline 7.87  (1.31) 7.64  (1.34) 5.85  (1.30) 8.90  (1.38)
36 months minus baseline 9.00  (1.53) 8.31  (1.60) 8.26  (1.50) 10.77  (1.63)
42 months minus baseline 10.35  (1.60) 8.24  (1.64) 7.97  (1.51) 10.61  (1.69)
48 months minus baseline 10.73  (1.87) 11.74  (1.97) 9.70  (1.82) 10.85  (2.04)
Average change from baseline 5.97  (0.70) 6.38  (0.70) 6.13  (0.71) 7.78  (0.70)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vitamin E, Placebo
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.10
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.80
Confidence Interval (2-Sided) 95%
-3.28 to -0.33
Estimation Comments Mean difference is the least squares mean changes from baseline for the vitamin E group minus the placebo group.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Memantine, Placebo
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.25
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.39
Confidence Interval (2-Sided) 95%
-2.85 to 0.07
Estimation Comments Mean difference is the least squares mean changes from baseline for the memantine group minus the placebo group.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Vitamin E + Memantine, Placebo
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.14
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.65
Confidence Interval (2-Sided) 95%
-3.12 to -0.17
Estimation Comments Mean difference is the least squares mean changes from baseline for the vitamin E + memantine group minus the placebo group.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Vitamin E, Vitamin E + Memantine
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.84
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.15
Confidence Interval (2-Sided) 95%
-1.32 to 1.63
Estimation Comments Mean difference is the least squares mean changes from baseline for the vitamin E + memantine group minus the vitamin E group.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Memantine, Vitamin E + Memantine
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.84
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.26
Confidence Interval (2-Sided) 95%
-1.72 to 1.21
Estimation Comments Mean difference is the least squares mean changes from baseline for the vitamin E + memantine group minus the memantine group.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Vitamin E, Memantine
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.84
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.41
Confidence Interval (2-Sided) 95%
-1.88 to 1.06
Estimation Comments Mean difference is the least squares mean changes from baseline for the vitamin E group minus the memantine group.
4.Primary Outcome
Title Neuropsychiatric Inventory Change From Baseline
Hide Description The Neuropsychiatric Inventory (NPI) assesses psychological and behavioral problems in patients with dementia. For each of twelve domains, there are four scores: frequency, severity, total frequency x severity, and caregiver distress. The frequency x severity total scores from each domain are summed for an overall total score that ranges from 0 to 144. The total caregiver distress scores are also summed for an overall total caregiver distress score that ranges from 0 to 60. The secondary endpoint for the trial will be the overall frequency times severity total score. Outcome analysis is average least square means change from baseline.
Time Frame 6, 12, 18, 24, 30, 36, 42 and 48 months minus baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat analysis that includes all participants with baseline and at least one follow-up measurement.
Arm/Group Title Vitamin E Memantine Vitamin E + Memantine Placebo
Hide Arm/Group Description:
Alpha-tocopherol (vitamin E in the form of dl-alpha-tocopheryl acetate), 2000 international units (IU) per day, taken as one 1000 IU hard-gelatin, liquid-filled capsules twice a day plus matching memantine placebos.
Memantine 20 mg per day, titrated over four weeks to a maintenance dosage of 10 mg pills taken twice a day plus matching vitamin E placebo.
2000 IU of Alpha-tocopherol (vitamin E) per day plus 20 mg memantine per day.
Matching placebo pills for vitamin E and memantine
Overall Number of Participants Analyzed 140 142 139 140
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
6 months minus baseline -1.24  (1.07) -0.20  (1.06) -0.47  (1.08) 0.46  (1.07)
12 months minus baseline -1.04  (1.21) 0.31  (1.22) -0.17  (1.22) 1.08  (1.24)
18 months minus baseline 0.93  (1.40) 1.18  (1.43) 0.41  (1.41) 4.06  (1.44)
24 months minus baseline 2.16  (1.74) 4.29  (1.79) 1.98  (1.77) 3.59  (1.84)
30 months minus baseline 3.21  (1.70) 2.62  (1.71) 2.16  (1.71) 1.66  (1.81)
36 months minus baseline 2.15  (1.97) 3.24  (2.07) 2.79  (1.95) 0.60  (2.16)
42 months minus baseline 0.81  (2.64) 3.63  (2.75) 1.85  (2.54) 3.64  (2.89)
48 months minus baseline -0.60  (2.53) 2.79  (2.60) 5.14  (2.54) 0.30  (2.79)
Average change from baseline 0.79  (1.00) 1.87  (1.00) 1.79  (1.00) 2.26  (1.01)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vitamin E, Placebo
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.94
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.46
Confidence Interval (2-Sided) 95%
-3.55 to 0.63
Estimation Comments Mean difference is the least squares mean changes from baseline for the vitamin E group minus the placebo group.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Memantine, Placebo
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.94
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.39
Confidence Interval (2-Sided) 95%
-2.47 to 1.70
Estimation Comments Mean difference is the least squares mean changes from baseline for the memantine group minus the placebo group.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Vitamin E + Memantine, Placebo
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.94
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.47
Confidence Interval (2-Sided) 95%
-2.57 to 1.63
Estimation Comments Mean difference is the least squares mean changes from baseline for the vitamin E + memantine group minus the placebo group.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Vitamin E, Vitamin E + Memantine
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.94
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
-1.09 to 3.07
Estimation Comments Mean difference is the least squares mean changes from baseline for the vitamin E + memantine group minus the vitamin E group.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Memantine, Vitamin E + Memantine
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.94
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.08
Confidence Interval (2-Sided) 95%
-2.16 to 1.99
Estimation Comments Mean difference is the least squares mean changes from baseline for the vitamin E + memantine group minus the memantine group.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Vitamin E, Memantine
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.94
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.08
Confidence Interval (2-Sided) 95%
-3.14 to 0.99
Estimation Comments Mean difference is the least squares mean changes from baseline for the vitamin E group minus the memantine group.
5.Primary Outcome
Title Caregiver Activity Survey Change From Baseline
Hide Description The Caregiver Activity Survey (CAS) was developed to measure the time caregivers spend aiding Alzheimer patients with their day-to-day activities. The CAS consists of six items that ask for an estimate in hours and minutes of the time that the caregiver spent during the previous 24 hours performing these particular activities. The six CAS items are as follows: 1) communication with the person, 2) using transportation, 3) dressing, 4) eating, 5) looking after one's appearance, and 6) supervising the person. The more caregiving hours the worse the patient's functioning level. Outcome analysis is average least square means change from baseline.
Time Frame 6, 12, 18, 24, 30, 36, 42 and 48 months minus baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat analysis that includes all participants with baseline and at least one follow-up measurement.
Arm/Group Title Vitamin E Memantine Vitamin E + Memantine Placebo
Hide Arm/Group Description:
Alpha-tocopherol (vitamin E in the form of dl-alpha-tocopheryl acetate), 2000 international units (IU) per day, taken as one 1000 IU hard-gelatin, liquid-filled capsules twice a day plus matching memantine placebos.
Memantine 20 mg per day, titrated over four weeks to a maintenance dosage of 10 mg pills taken twice a day plus matching vitamin E placebo.
2000 IU of Alpha-tocopherol (vitamin E) per day plus 20 mg memantine per day.
Matching placebo pills for vitamin E and memantine
Overall Number of Participants Analyzed 140 142 139 140
Least Squares Mean (Standard Error)
Unit of Measure: hours per day
6 months minus baseline -0.93  (0.82) 0.99  (0.81) 1.08  (0.83) 1.20  (0.82)
12 months minus baseline -0.18  (1.00) 2.72  (1.01) 1.39  (1.01) 1.89  (1.04)
18 months minus baseline 2.12  (1.20) 3.77  (1.22) 2.69  (1.20) 3.16  (1.23)
24 months minus baseline 1.60  (1.09) 3.06  (1.13) 2.82  (1.11) 3.45  (1.16)
30 months minus baseline 4.14  (1.22) 5.22  (1.25) 3.41  (1.24) 4.36  (1.32)
36 months minus baseline 7.69  (2.30) 5.72  (2.43) 4.90  (2.24) 10.68  (2.51)
42 months minus baseline 4.95  (1.81) 9.46  (1.89) 5.48  (1.73) 10.62  (1.99)
48 months minus baseline 10.17  (2.74) 9.27  (2.80) 13.80  (2.74) 12.17  (3.03)
Average change from baseline 3.35  (0.78) 5.52  (0.78) 5.00  (0.78) 5.14  (0.79)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vitamin E, Placebo
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.12
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.79
Confidence Interval (2-Sided) 95%
-3.35 to -0.23
Estimation Comments Mean difference is the least squares mean changes from baseline for the vitamin E group minus the placebo group.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Memantine, Placebo
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.86
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.38
Confidence Interval (2-Sided) 95%
-1.18 to 1.94
Estimation Comments Mean difference is the least squares mean changes from baseline for the memantine group minus the placebo group.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Vitamin E + Memantine, Placebo
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.86
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.14
Confidence Interval (2-Sided) 95%
-1.70 to 1.42
Estimation Comments Mean difference is the least squares mean changes from baseline for the vitamin E + memantine group minus the placebo group.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Vitamin E, Vitamin E + Memantine
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.14
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.65
Confidence Interval (2-Sided) 95%
0.11 to 3.19
Estimation Comments Mean difference is the least squares mean changes from baseline for the vitamin E + memantine group minus the vitamin E group.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Memantine, Vitamin E + Memantine
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.86
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.52
Confidence Interval (2-Sided) 95%
-2.07 to 1.02
Estimation Comments Mean difference is the least squares mean changes from baseline for the vitamin E + memantine group minus the memantine group.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Vitamin E, Memantine
Comments Longitudinal analysis to assess the average treatment effect over 48 months with visits at 6, 12, 18, 24, 30, 36, 42 and 48 months using all available data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments p-value is adjusted for 6 treatment group comparisons
Method Mixed Models Analysis
Comments Mixed effects model assuming data missing at random, adjusted for medical center as a random effect and for the baseline outcome score.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.17
Confidence Interval (2-Sided) 95%
-3.71 to -0.63
Estimation Comments Mean difference is the least squares mean changes from baseline for the vitamin E group minus the memantine group.
6.Secondary Outcome
Title Dependence Scale: Time to Event Analysis (Increase of of One Dependence Level)
Hide Description The Dependence Scale assesses the level of assistance needed by patients with Alzheimer's disease for activities of daily living. The scale yields six levels of dependence: no assistance required (Level 0); requires occasional reminders (Level 1); requires frequent reminders and/or help with household chores (Level 2); needs daily supervision (Level 3); needs to be dressed, toileted or fed (Level 4); needs to be transferred, diapered or tube fed (Level 5).
Time Frame Every 6 months to a maximum of 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat analysis that includes all participants with baseline and at least one follow-up measurement.
Arm/Group Title Vitamin E Memantine Vitamin E + Memantine Placebo
Hide Arm/Group Description:
Alpha-tocopherol (vitamin E in the form of dl-alpha-tocopheryl acetate), 2000 international units (IU) per day, taken as one 1000 IU hard-gelatin, liquid-filled capsules twice a day plus matching memantine placebos.
Memantine 20 mg per day, titrated over four weeks to a maintenance dosage of 10 mg pills taken twice a day plus matching vitamin E placebo.
2000 IU of Alpha-tocopherol (vitamin E) per day plus 20 mg memantine per day.
Matching placebo pills for vitamin E and memantine
Overall Number of Participants Analyzed 140 142 139 140
Measure Type: Number
Unit of Measure: participants
80 87 87 79
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vitamin E, Memantine, Vitamin E + Memantine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.69
Comments p- value is unadjusted for multiple comparisons because its a 3 degrees of freedom test for any treatment group differences
Method Log Rank
Comments 3 degrees of freedom test
7.Other Pre-specified Outcome
Title All-cause Mortality
Hide Description Survival analysis of death from any cause.
Time Frame up to 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat analysis that includes all randomized participants.
Arm/Group Title Vitamin E Memantine Vitamin E + Memantine Placebo
Hide Arm/Group Description:
Alpha-tocopherol (vitamin E in the form of dl-alpha-tocopheryl acetate), 2000 international units (IU) per day, taken as one 1000 IU hard-gelatin, liquid-filled capsules twice a day plus matching memantine placebos.
Memantine 20 mg per day, titrated over four weeks to a maintenance dosage of 10 mg pills taken twice a day plus matching vitamin E placebo.
2000 IU of Alpha-tocopherol (vitamin E) per day plus 20 mg memantine per day.
Matching placebo pills for vitamin E and memantine
Overall Number of Participants Analyzed 152 155 154 152
Measure Type: Number
Unit of Measure: participants
26 39 32 31
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vitamin E, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.31
Comments p-value is unadjusted for multiple comparisons
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.67 to 1.13
Estimation Comments Hazard ratio is for vitamin E group relative to the placebo group.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Memantine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.47
Comments p-value is unadjusted for multiple comparisons
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.06
Confidence Interval (2-Sided) 95%
0.91 to 1.24
Estimation Comments Hazard ratio is for the memantine group relative to the placebo group.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Vitamin E + Memantine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.80
Comments p-value is unadjusted for multiple comparisons
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.57 to 1.54
Estimation Comments Hazard ratio is for the vitamin E + memantine group relative to the placebo group.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Vitamin E Memantine Vitamin E + Memantine Placebo
Hide Arm/Group Description Alpha-tocopherol (vitamin E in the form of dl-alpha-tocopheryl acetate), 2000 international units (IU) per day, taken as one 1000 IU hard-gelatin, liquid-filled capsules twice a day plus matching memantine placebos. Memantine 20 mg per day, titrated over four weeks to a maintenance dosage of 10 mg pills taken twice a day plus matching vitamin E placebo. 2000 IU of Alpha-tocopherol (vitamin E) per day plus 20 mg memantine per day. Matching placebo pills for vitamin E and memantine
All-Cause Mortality
Vitamin E Memantine Vitamin E + Memantine Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Vitamin E Memantine Vitamin E + Memantine Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   82/152 (53.95%)      84/155 (54.19%)      83/154 (53.90%)      95/152 (62.50%)    
Blood and lymphatic system disorders         
Anaemia  1  1/152 (0.66%)  1 1/155 (0.65%)  1 0/154 (0.00%)  0 1/152 (0.66%)  1
Microcytic anaemia  1  1/152 (0.66%)  1 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Blood and lymphatic system disorders [1]  2/152 (1.32%)  2 2/155 (1.29%)  2 0/154 (0.00%)  0 1/152 (0.66%)  1
Cardiac disorders         
Acute coronary syndrome  1  1/152 (0.66%)  2 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Acute myocardial infarction  1  1/152 (0.66%)  1 3/155 (1.94%)  3 1/154 (0.65%)  1 1/152 (0.66%)  1
Angina pectoris  1  0/152 (0.00%)  0 1/155 (0.65%)  1 1/154 (0.65%)  1 0/152 (0.00%)  0
Angina unstable  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 2/152 (1.32%)  2
Arrhythmia  1  1/152 (0.66%)  1 1/155 (0.65%)  1 0/154 (0.00%)  0 2/152 (1.32%)  4
Arteriosclerosis coronary artery  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Atrial fibrillation  1  1/152 (0.66%)  1 1/155 (0.65%)  1 3/154 (1.95%)  3 3/152 (1.97%)  5
Atrial flutter  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Atrioventricular block first degree  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Atrioventricular block second degree  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Bradycardia  1  1/152 (0.66%)  1 1/155 (0.65%)  1 0/154 (0.00%)  0 2/152 (1.32%)  2
Cardiac arrest  1  3/152 (1.97%)  3 1/155 (0.65%)  1 3/154 (1.95%)  3 1/152 (0.66%)  1
Cardiac failure  1  0/152 (0.00%)  0 3/155 (1.94%)  3 1/154 (0.65%)  1 2/152 (1.32%)  2
Cardiac failure acute  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Cardiac failure chronic  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Cardiac failure congestive  1  4/152 (2.63%)  8 2/155 (1.29%)  2 4/154 (2.60%)  5 5/152 (3.29%)  7
Cardio-respiratory arrest  1  1/152 (0.66%)  1 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Cardiomyopathy  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Cardiovascular disorder  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Cor pulmonale  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Coronary artery disease  1  1/152 (0.66%)  1 1/155 (0.65%)  1 0/154 (0.00%)  0 1/152 (0.66%)  1
Coronary artery occlusion  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Hypertensive cardiomyopathy  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Ischaemic cardiomyopathy  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Mitral valve incompetence  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Myocardial infarction  1  6/152 (3.95%)  7 5/155 (3.23%)  5 3/154 (1.95%)  3 4/152 (2.63%)  5
Nodal arrhythmia  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Cardiac Disorders  1 [2]  19/152 (12.50%)  30 16/155 (10.32%)  23 19/154 (12.34%)  21 20/152 (13.16%)  26
Eye disorders         
Cataract  1  1/152 (0.66%)  1 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Gastrointestinal disorders         
Abdominal pain  1  1/152 (0.66%)  1 1/155 (0.65%)  1 0/154 (0.00%)  0 1/152 (0.66%)  1
Abdominal pain upper  1  1/152 (0.66%)  1 0/155 (0.00%)  0 1/154 (0.65%)  1 1/152 (0.66%)  1
Constipation  1  1/152 (0.66%)  1 1/155 (0.65%)  1 1/154 (0.65%)  1 0/152 (0.00%)  0
Diarrhoea  1  0/152 (0.00%)  0 1/155 (0.65%)  1 2/154 (1.30%)  2 1/152 (0.66%)  1
Diverticulum  1  1/152 (0.66%)  1 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Diverticulum intestinal  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Diverticulum intestinal haemorrhagic  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 1/152 (0.66%)  1
Dysphagia  1  0/152 (0.00%)  0 1/155 (0.65%)  1 1/154 (0.65%)  1 0/152 (0.00%)  0
Gastrointestinal disorder  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Gastrointestinal haemorrhage  1  1/152 (0.66%)  1 3/155 (1.94%)  3 0/154 (0.00%)  0 1/152 (0.66%)  1
Gastrointestinal obstruction  1  0/152 (0.00%)  0 1/155 (0.65%)  1 1/154 (0.65%)  1 0/152 (0.00%)  0
Gastrointestinal ulcer haemorrhage  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Haematochezia  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Inguinal hernia  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Intestinal obstruction  1  0/152 (0.00%)  0 0/155 (0.00%)  0 2/154 (1.30%)  2 0/152 (0.00%)  0
Intestinal perforation  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Large intestinal ulcer haemorrhage  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Oesophageal disorder  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Pancreatitis  1  2/152 (1.32%)  2 2/155 (1.29%)  2 0/154 (0.00%)  0 1/152 (0.66%)  1
Pancreatitis acute  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Pancreatitis relapsing  1  0/152 (0.00%)  0 1/155 (0.65%)  2 0/154 (0.00%)  0 0/152 (0.00%)  0
Peptic ulcer  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Pharyngoesophageal diverticulum  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Rectal haemorrhage  1  1/152 (0.66%)  1 1/155 (0.65%)  1 0/154 (0.00%)  0 1/152 (0.66%)  1
Small intestinal haemorrhage  1  0/152 (0.00%)  0 1/155 (0.65%)  2 0/154 (0.00%)  0 0/152 (0.00%)  0
Small intestinal obstruction  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Upper gastrointestinal haemorrhage  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Vomiting  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Gastrointestinal Disorders  1 [3]  13/152 (8.55%)  13 14/155 (9.03%)  18 12/154 (7.79%)  13 8/152 (5.26%)  10
General disorders         
Adverse drug reaction  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 2/152 (1.32%)  2
Asthenia  1  0/152 (0.00%)  0 1/155 (0.65%)  1 1/154 (0.65%)  1 1/152 (0.66%)  1
Chest pain  1  3/152 (1.97%)  3 1/155 (0.65%)  1 3/154 (1.95%)  5 3/152 (1.97%)  4
Complication of device insertion  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Cyst  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Death  1  2/152 (1.32%)  2 4/155 (2.58%)  4 1/154 (0.65%)  1 3/152 (1.97%)  3
General physical health deterioration  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Hernia  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Implant site pain  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Malaise  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Medical device complication  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Multi-organ failure  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Non-cardiac chest pain  1  2/152 (1.32%)  2 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Oedema  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Pyrexia  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 1/152 (0.66%)  1
Stent-graft endoleak  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Sudden cardiac death  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
General Disorders  1 [4]  9/152 (5.92%)  9 7/155 (4.52%)  8 8/154 (5.19%)  10 14/152 (9.21%)  15
Hepatobiliary disorders         
Cholecystitis acute  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Cholelithiasis  1  1/152 (0.66%)  1 2/155 (1.29%)  2 1/154 (0.65%)  1 0/152 (0.00%)  0
Gallbladder disorder  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Hepatobiliary Disorders  1 [5]  1/152 (0.66%)  1 2/155 (1.29%)  2 1/154 (0.65%)  1 2/152 (1.32%)  2
Infections and infestations         
Abscess limb  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Acarodermatitis  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Bacteraemia  1  0/152 (0.00%)  0 0/155 (0.00%)  0 2/154 (1.30%)  2 0/152 (0.00%)  0
Bronchitis  1  0/152 (0.00%)  0 2/155 (1.29%)  2 1/154 (0.65%)  1 0/152 (0.00%)  0
Bronchopneumonia  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Cellulitis  1  2/152 (1.32%)  2 3/155 (1.94%)  5 3/154 (1.95%)  3 0/152 (0.00%)  0
Cystitis  1  1/152 (0.66%)  1 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Diverticulitis  1  1/152 (0.66%)  1 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Ear infection  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Escherichia infection  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Escherichia urinary tract infection  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Fungal infection  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Gastritis viral  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Gastroenteritis  1  1/152 (0.66%)  1 2/155 (1.29%)  2 0/154 (0.00%)  0 0/152 (0.00%)  0
Gastroenteritis viral  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Gastrointestinal infection  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Infected cyst  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Infection  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Latent tuberculosis  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Lobar pneumonia  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Mycobacterium avium complex infection  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Nasal abscess  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Osteomyelitis  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Pneumonia  1  8/152 (5.26%)  11 8/155 (5.16%)  9 15/154 (9.74%)  15 5/152 (3.29%)  5
Sepsis  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 1/152 (0.66%)  1
Sporotrichosis  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Staphylococcal infection  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Tooth infection  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Upper respiratory tract infection  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Urinary tract infection  1  8/152 (5.26%)  8 8/155 (5.16%)  8 7/154 (4.55%)  13 4/152 (2.63%)  5
Urosepsis  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Infections  1 [6]  19/152 (12.50%)  29 23/155 (14.84%)  31 31/154 (20.13%)  44 11/152 (7.24%)  13
Injury, poisoning and procedural complications         
Accident at home  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Carbon monoxide poisoning  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Confusion postoperative  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Drug administration error  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Fall  1  15/152 (9.87%)  17 14/155 (9.03%)  16 12/154 (7.79%)  14 15/152 (9.87%)  18
Femur fracture  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Haemodialysis-induced symptom  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Hip fracture  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Limb injury  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Post procedural complication  1  3/152 (1.97%)  3 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Post procedural pulmonary embolism  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Subdural haematoma  1  0/152 (0.00%)  0 1/155 (0.65%)  1 1/154 (0.65%)  2 0/152 (0.00%)  0
Injury or Procedural Complications  1 [7]  18/152 (11.84%)  22 15/155 (9.68%)  18 15/154 (9.74%)  17 18/152 (11.84%)  21
Investigations         
Blood glucose increased  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Bronchoscopy  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Coagulation factor decreased  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Cystoscopy  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Electrocardiogram change  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Heart rate increased  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Heart rate irregular  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Urine output decreased  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Weight decreased  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Investigations  1 [8]  2/152 (1.32%)  2 2/155 (1.29%)  2 4/154 (2.60%)  4 1/152 (0.66%)  1
Metabolism and nutrition disorders         
Dehydration  1  2/152 (1.32%)  3 1/155 (0.65%)  1 0/154 (0.00%)  0 3/152 (1.97%)  3
Diabetes mellitus inadequate control  1  1/152 (0.66%)  1 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Diabetic ketoacidosis  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  3 0/152 (0.00%)  0
Failure to thrive  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 2/152 (1.32%)  2
Gout  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Hyperglycaemia  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Hyperglycaemic hyperosmolar nonketotic syndrome  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Hypoglycaemia  1  1/152 (0.66%)  1 2/155 (1.29%)  2 3/154 (1.95%)  3 0/152 (0.00%)  0
Hypophagia  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Hypovolaemia  1  0/152 (0.00%)  0 3/155 (1.94%)  3 0/154 (0.00%)  0 0/152 (0.00%)  0
Metabolism and Nutrition Disorders  1 [9]  3/152 (1.97%)  4 7/155 (4.52%)  7 7/154 (4.55%)  9 6/152 (3.95%)  6
Musculoskeletal and connective tissue disorders         
Arthralgia  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Bursitis  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Pain in extremity  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Rotator cuff syndrome  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Acute myeloid leukaemia  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Bladder cancer  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Chronic lymphocytic leukaemia  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Colon cancer  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Colon cancer metastatic  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Colon cancer stage III  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Gastric cancer  1  1/152 (0.66%)  1 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Laryngeal cancer  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  2 0/152 (0.00%)  0
Leukaemia  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Lung cancer metastatic  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Lung neoplasm malignant  1  0/152 (0.00%)  0 2/155 (1.29%)  2 0/154 (0.00%)  0 1/152 (0.66%)  1
Mesothelioma  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Neoplasm malignant  1  1/152 (0.66%)  1 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Non-Hodgkin's lymphoma  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Non-small cell lung cancer  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Oesophageal cancer metastatic  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Oesophageal carcinoma  1  0/152 (0.00%)  0 1/155 (0.65%)  2 0/154 (0.00%)  0 0/152 (0.00%)  0
Pancreatic carcinoma  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  2 0/152 (0.00%)  0
Prostate cancer  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Neoplasms  1 [10]  4/152 (2.63%)  4 7/155 (4.52%)  8 4/154 (2.60%)  6 6/152 (3.95%)  6
Nervous system disorders         
Altered state of consciousness  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Aphasia  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Balance disorder  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Brain mass  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Carotid artery occlusion  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 1/152 (0.66%)  1
Carotid artery stenosis  1  0/152 (0.00%)  0 1/155 (0.65%)  2 0/154 (0.00%)  0 0/152 (0.00%)  0
Cerebral amyloid angiopathy  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Cerebral infarction  1  0/152 (0.00%)  0 0/155 (0.00%)  0 2/154 (1.30%)  2 0/152 (0.00%)  0
Cerebrovascular accident  1  2/152 (1.32%)  2 1/155 (0.65%)  1 2/154 (1.30%)  2 4/152 (2.63%)  4
Cerebrovascular insufficiency  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Convulsion  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 1/152 (0.66%)  1
Dementia  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 3/152 (1.97%)  3
Dementia Alzheimer's type  1  3/152 (1.97%)  3 3/155 (1.94%)  3 3/154 (1.95%)  3 2/152 (1.32%)  2
Dizziness  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Dysarthria  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Grand mal convulsion  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Haemorrhage intracranial  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Haemorrhagic stroke  1  2/152 (1.32%)  2 1/155 (0.65%)  1 1/154 (0.65%)  1 0/152 (0.00%)  0
Headache  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Hypoglycaemic unconsciousness  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Ischaemic stroke  1  1/152 (0.66%)  1 1/155 (0.65%)  1 0/154 (0.00%)  0 2/152 (1.32%)  2
Loss of consciousness  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 1/152 (0.66%)  1
Mental impairment  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Motor dysfunction  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Syncope  1  2/152 (1.32%)  2 2/155 (1.29%)  2 2/154 (1.30%)  2 4/152 (2.63%)  5
Transient ischaemic attack  1  1/152 (0.66%)  2 1/155 (0.65%)  1 2/154 (1.30%)  2 1/152 (0.66%)  1
Unresponsive to stimuli  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Nervous System Disorders  1 [11]  12/152 (7.89%)  15 15/155 (9.68%)  18 17/154 (11.04%)  18 19/152 (12.50%)  21
Psychiatric disorders         
Abnormal behaviour  1  0/152 (0.00%)  0 2/155 (1.29%)  2 0/154 (0.00%)  0 0/152 (0.00%)  0
Aggression  1  2/152 (1.32%)  3 2/155 (1.29%)  2 1/154 (0.65%)  1 2/152 (1.32%)  2
Agitation  1  1/152 (0.66%)  1 1/155 (0.65%)  1 1/154 (0.65%)  1 2/152 (1.32%)  2
Confusional state  1  4/152 (2.63%)  4 0/155 (0.00%)  0 1/154 (0.65%)  1 1/152 (0.66%)  1
Depression  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 1/152 (0.66%)  1
Hallucination  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Mental status changes  1  1/152 (0.66%)  1 2/155 (1.29%)  2 0/154 (0.00%)  0 1/152 (0.66%)  1
Parasomnia  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Psychotic behaviour  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Psychotic disorder  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Self injurious behaviour  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Suicidal ideation  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  2 0/152 (0.00%)  0
Psychiatric Disorders  1 [12]  8/152 (5.26%)  10 10/155 (6.45%)  10 5/154 (3.25%)  7 5/152 (3.29%)  5
Renal and urinary disorders         
Bladder obstruction  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Haematuria  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 1/152 (0.66%)  1
Nephrolithiasis  1  1/152 (0.66%)  1 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Polyuria  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 1/152 (0.66%)  1
Renal failure  1  1/152 (0.66%)  1 1/155 (0.65%)  1 1/154 (0.65%)  1 1/152 (0.66%)  1
Renal failure acute  1  0/152 (0.00%)  0 1/155 (0.65%)  1 1/154 (0.65%)  1 3/152 (1.97%)  3
Renal failure chronic  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Renal and Urinary Disorders  [13]  2/152 (1.32%)  2 5/155 (3.23%)  5 4/154 (2.60%)  4 6/152 (3.95%)  6
Reproductive system and breast disorders         
Epididymitis  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Prostatomegaly  1  1/152 (0.66%)  1 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Aspiration  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Asthma  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  2
Choking  1  0/152 (0.00%)  0 1/155 (0.65%)  2 0/154 (0.00%)  0 0/152 (0.00%)  0
Chronic obstructive pulmonary disease  1  2/152 (1.32%)  8 3/155 (1.94%)  3 2/154 (1.30%)  2 4/152 (2.63%)  6
Dyspnoea  1  1/152 (0.66%)  1 0/155 (0.00%)  0 1/154 (0.65%)  1 1/152 (0.66%)  3
Epistaxis  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Pneumonia aspiration  1  0/152 (0.00%)  0 2/155 (1.29%)  3 2/154 (1.30%)  2 4/152 (2.63%)  4
Pulmonary embolism  1  0/152 (0.00%)  0 2/155 (1.29%)  2 1/154 (0.65%)  1 0/152 (0.00%)  0
Pulmonary haemorrhage  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Pulmonary oedema  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Pulmonary thrombosis  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Respiratory depression  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Respiratory failure  1  1/152 (0.66%)  1 1/155 (0.65%)  1 1/154 (0.65%)  1 1/152 (0.66%)  1
Respiratory Disorders  1 [14]  5/152 (3.29%)  12 9/155 (5.81%)  11 7/154 (4.55%)  8 11/152 (7.24%)  17
Skin and subcutaneous tissue disorders         
Decubitus ulcer  1  0/152 (0.00%)  0 1/155 (0.65%)  2 0/154 (0.00%)  0 0/152 (0.00%)  0
Skin ulcer  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Skin Disorders  1 [15]  0/152 (0.00%)  0 1/155 (0.65%)  3 0/154 (0.00%)  0 0/152 (0.00%)  0
Social circumstances         
Respite care  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Treatment noncompliance  1  1/152 (0.66%)  1 1/155 (0.65%)  1 0/154 (0.00%)  0 2/152 (1.32%)  2
Social Circumstances  1 [16]  1/152 (0.66%)  2 1/155 (0.65%)  1 0/154 (0.00%)  0 3/152 (1.97%)  3
Surgical and medical procedures         
Arterial bypass operation  1  1/152 (0.66%)  2 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Bladder neoplasm surgery  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Cardiac operation  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Cardiac pacemaker battery replacement  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Cardiac pacemaker insertion  1  1/152 (0.66%)  1 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Cardiac pacemaker replacement  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Cholecystectomy  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Coronary arterial stent insertion  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  2
Drug detoxification  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Hip arthroplasty  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Hospice care  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Knee arthroplasty  1  1/152 (0.66%)  1 2/155 (1.29%)  4 1/154 (0.65%)  2 1/152 (0.66%)  1
Renal stone removal  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Spinal laminectomy  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Surgery  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Transurethral prostatectomy  1  0/152 (0.00%)  0 2/155 (1.29%)  2 1/154 (0.65%)  1 0/152 (0.00%)  0
Surgical and Medical Procedures  1 [17]  9/152 (5.92%)  10 5/155 (3.23%)  7 5/154 (3.25%)  6 5/152 (3.29%)  6
Vascular disorders         
Aortic aneurysm  1  2/152 (1.32%)  2 0/155 (0.00%)  0 2/154 (1.30%)  2 0/152 (0.00%)  0
Aortic aneurysm rupture  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Aortic disorder  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Arteriosclerosis  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 2/152 (1.32%)  2
Deep vein thrombosis  1  0/152 (0.00%)  0 3/155 (1.94%)  4 0/154 (0.00%)  0 0/152 (0.00%)  0
Haemorrhage  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 1/152 (0.66%)  1
Hypertension  1  0/152 (0.00%)  0 1/155 (0.65%)  1 2/154 (1.30%)  4 1/152 (0.66%)  1
Hypotension  1  0/152 (0.00%)  0 0/155 (0.00%)  0 0/154 (0.00%)  0 2/152 (1.32%)  2
Peripheral embolism  1  0/152 (0.00%)  0 1/155 (0.65%)  1 0/154 (0.00%)  0 0/152 (0.00%)  0
Shock  1  0/152 (0.00%)  0 0/155 (0.00%)  0 1/154 (0.65%)  1 0/152 (0.00%)  0
Thrombosis  1  1/152 (0.66%)  1 0/155 (0.00%)  0 0/154 (0.00%)  0 0/152 (0.00%)  0
Vascular Disorders  1 [18]  4/152 (2.63%)  4 5/155 (3.23%)  6 6/154 (3.90%)  9 6/152 (3.95%)  6
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDra 15.0
[1]
Sum of all adverse event terms in the Blood and Lymphatic Disorders System Organ Class
[2]
Sum of all adverse event terms in the Cardiac Disorders System Organ Class
[3]
Sum of all adverse event terms in the Gastrointestinal Disorders System Organ Class
[4]
Sum of all adverse event terms in the General Disorders System Organ Class
[5]
Sum of all adverse event terms in the Hepatobiliary Disorders System Organ Class
[6]
Sum of all adverse event terms in the Infections and Infestations System Organ Class
[7]
Sum of all adverse event terms in the Injury, Poisoning and Procedural Complications System Organ Class
[8]
Sum of all adverse event terms in the Investigations System Organ Class
[9]
Sum of all adverse event terms in the Matabolism and Nutrition Disorders System Organ Class
[10]
Sum of all adverse event terms in the Neoplasm System Organ Class
[11]
Sum of all adverse event terms in the Nervous System Disorders System Organ Class
[12]
Sum of all adverse event terms in the Psychiatric Disorders System Organ Class
[13]
Sum of all adverse event terms in the Renal and Urinary Disorders System Organ Class
[14]
Sum of all adverse event terms in the Respiratory Disorders System Organ Class
[15]
Sum of all adverse event terms in the Skin Disorders System Organ Class
[16]
Sum of all adverse event terms in the Social Circumstances System Organ Class
[17]
Sum of all adverse event terms in the Surgical and Medical Procedures System Organ Class
[18]
Sum of all adverse event terms in the Vascular Disorders System Organ Class
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Vitamin E Memantine Vitamin E + Memantine Placebo
Affected / at Risk (%) # Events