Table 1: Baseline characteristics of published trials [54].
|
Treatment |
Year |
Author, year |
Clinicaltrials identifier |
Number of participants |
Mean age
in years |
Duration of the study (months) |
Primary endpoint |
Multi
center |
Countries |
Placebo-controlled trial |
Dementia stage |
Adverse events (AE) Treatment emergent adverse events (TEAE) Serious Adverse Events (SAE) |
|
Donepezil |
2006 |
Moraes WADS, 2006 [12] |
NCT00480870 |
40 |
77.4 |
6 |
Sleep |
Yes |
Brazil |
Yes |
Mild to moderate |
AE (include SAE): 8.6% donepezil group, UK** placebo group SAE: UK** |
|
Donepezil |
2006 |
Müller T,
2006 [13] |
NCT00165815 |
24 |
71.1 |
3 |
Cognition, Functionnal Autonomy, Adverse
drug reactions, Clinician’s clinical impression, Behaviour |
Yes |
Ireland,
Germany |
Yes |
Mild to moderate
|
UK** |
|
Donepezil |
2006 |
Winblad B, 2006 [14] |
NCT00630851 |
249 |
84.9 |
6 |
Cognition |
Yes |
Sweden |
Yes |
Severe |
AE (include SAE): 82% donepezil group, 76% placebo group SAE: 24% donepezil group, 26% placebo group |
|
Donepezil |
2008 |
Lopez OL,
2008 [15] |
NCT00230568 |
106 |
67 |
3 |
Cognition,
Behaviour |
Yes |
United States |
No |
Mild to moderate
|
TEAE (include SAE): 46.7% SAE: 6.7% |
|
Donepezil |
2008 |
Mittelman MS, 2008 [16] |
NCT00467766 |
158 |
74 |
24 |
Caregiver |
Yes |
United States, Great Britain, Australia |
No |
Mild to moderate |
UK** |
|
Donepezil |
2009 |
Doody RS, 2009 [17] |
NCT00293176 |
821 |
70 |
12 |
Cognition |
Yes |
United States |
Yes |
Mild cognitive impairment (MMS : 24 to 28) |
AE (include SAE): 81.3% donepezil group, 69% placebo group SAE: 11% in each group |
|
Donepezil |
2010 |
Chung KA,
2010 [18] |
NCT00912808 |
23 |
68.4 |
2 |
Capacity of mobility
measure |
No |
United States |
Yes |
Parkinson desease, with MMS > 24 (falling
or nearly falling 2 or more times per week) |
AE (include SAE): 35% donepezil group, UK** placebo group SAE: UK** |
|
Donepezil |
2010 |
Doody RS, 2010 [19] |
NCT00934375 |
145 |
72.6 |
7 |
Adverse drug reactions |
Yes |
United States |
Yes |
Mild cognitive impairment |
AE (include SAE): 57% donepezil group, 62% placebo group TEAE: 41.5% placebo group, 23.5% donepezil group SAE: 4.4% donépézil group, 2.6% placebo
group |
|
Donepezil |
2010 |
Farlow MR, 2010 [20] |
NCT00478205 |
1434 |
73.8 |
6 |
Cognition, Clinician’s clinical impression , Adverse drug reactions |
Yes |
Australia, United States, Europe, South Africa, Asia, South America |
No |
Moderate to severe
|
TEAE (include SAE): 63.7% à 73.7% dependinf on
the donepezil dose SAE: 8.3% to 9.6% depending on the donepezil dose |
|
Donepezil |
2011 |
Alvarez XA,
2011 [21] |
NCT00911807 |
197-217 |
75.2 |
7 |
Cognition, Clinician’s clinical impression |
Yes |
Spain |
No |
Mild to moderate
|
AE: 60%
SAE: 1.5% |
|
Donepezil |
2012 |
Andersen F,
2012 [22] |
NCT00443014 |
187 |
81 |
12 |
Cognition |
Yes |
Norway |
Yes |
Mild to moderate |
Partial data: 18.9% in donepezil group reported gasrointestinal
réactions |
|
Donepezil |
2012 |
Mori E, 2012 [23] |
NCT00543855 |
137 |
78.7 |
3 |
Cognition, Behavior, Clinician’s clinical impression, Caregiver,
Capacity of mobility measure |
Yes |
Japan |
Yes |
Mild to moderate
|
AE (include SAE): 70.6% placebo group, 68.6% to 86.5% depending on the
donepezil dose SAE: 5.9% placebo group, 5.7% to 10.8% depending on the donepezil dose |
|
Donepezil |
2012 |
Tariot P, 2012 [24] |
NCT00566501 |
915 |
74.2 |
12 |
Adverse drug reactions |
Yes |
United States |
No |
Moderate to severe
|
AE (include SAE): 74.7%
SAE: 15% |
|
Donepezil |
2013 |
Ikeda M, 2013
[25] |
NCT00598650 |
108 |
78.9 |
13 |
Cognition, Behavior, Adverse drug reactions |
Yes |
Japan |
No |
Mild, moderate,
severe |
AE (include SAE): 94% SAE: 23% |
|
Donepezil |
2015 |
Mori E, 2015 [26] |
NCT01278407 |
100 |
77.9 |
13 |
Cognition, Behavior, Adverse drug reactions |
Yes |
Japan |
No |
Mild to moderate
|
AE (include SAE): 89.2% to 93.8% TEAE: 47.9% to 59.5% SAE: 12,5% à 24,3% |
|
Galantamine |
2000 |
Raskind MA, 2000 [27] |
NCT00253201 |
636 |
75 |
6 |
Cognition, Clinician’s clinical impression |
Yes |
United States |
Yes |
Mild to moderate |
AE (include SAE): 79% placebo group, 92% galantamine
group SAE: 14% galantamine group, UK**
placebo group |
|
Galantamine |
2000 |
Wilcock GK, 2000 [28] |
NCT00253188 |
653 |
72 |
6 |
Cognition, Clinician’s clinical
impression, caregiver |
Yes |
Great Britain |
Yes |
Mild to moderate |
AE (include SAE): 77% placebo group, 85% galantamine
group SAE: 12% placebo group, 13% galantamine
group |
|
Galantamine |
2001 |
Rockwood K, 2001 [29] |
NCT00253227 |
387 |
75 |
3 |
Cognition, Clinician’s clinical impression |
Yes |
Great Britain, United States, New Zealand, South Africa, Australia,
Canada |
Yes |
Mild to moderate
|
AE (include SAE): 63% placebo group, 86% galantamine
group
SAE: 6% placebo group, 8% galantamine group |
|
Galantamine |
2002 |
Erkinjuntti T, 2002 [30] |
NCT00261573 |
593 |
75 |
6 |
Cognition, Clinician’s clinical impression |
Yes |
Great Britain, United States, Canada, Germany, Finland |
Yes |
Mild to moderate
|
AE (include SAE): 67.9% placebo group, 83.3% galantamine
group SAE: UK** |
|
Galantamine |
2005 |
Brodaty H, 2005 [31] |
NCT00253214 |
971 |
UK** |
6 |
Cognition, Clinician’s clinical impression |
Yes |
Australia |
Yes |
Mild to moderate
|
UK** |
|
Galantamine |
2007 |
Edwards K,
2007 [32] |
NCT00230997 |
50 |
UK** |
6 |
Cognition,
Behaviour, Clinician’s clinical
impression |
Yes |
United States |
No |
Mild to moderate
|
UK** |
|
Galantamine |
2009 |
Burns A, 2009
[2] |
NCT00216593 |
207 |
84 |
6 |
Cognition, Functional autonomy |
Yes |
Great Britain, Belgium |
Yes |
Severe |
AE (include SAE): 88% galantamine group, 89%
placebo group
TEAE: 34% galantamine group, 28% placebo
group SAE: 18% galantamine group, 21% placebo
group |
|
Galantamine |
2011 |
Scarpini E, 2011 [33] |
NCT00216502 |
254 |
74 |
36 |
Cognition, Clinician’s clinical
impression, Adverse drug reactions |
Yes |
Germany, Great Britain, Italy |
Yes |
Mild to moderate |
TEAE (exclude SAE): 27% placebo group, 34% galantamine
group SAE: 6.3% placebo group, 14.5% galantamine
group |
|
Galantamine |
2014 |
Caramelli P, 2014 [34] |
NCT00814658 |
21 |
76 |
6 |
Cognition, Quality of life |
Yes |
Brazil |
No |
Mild to moderate
|
AE (exclude SAE): 85% SAE: 10% |
|
Galantamine |
2015 |
Lee JH, 2015
[35] |
NCT01054976 |
92 |
72 |
3 |
Cognition, Functional autonomy |
Yes |
Korea |
No |
Mild to moderate
|
AE (include SAE): 50%
SAE: 8,7% |
|
Galantamine, Donepezil |
2008 |
Whyte EM,
2008 [36] |
NCT00227994 |
40 |
70 |
3 |
Cognition, Capacity of mobility measure |
Yes |
United States |
No |
1 standard deviation below age-matched norms on the Hopkins Verbal
Learning Test |
UK** |
|
Memantine |
2009 |
Aarsland D, 2009 [37] |
NCT00630500 |
72 |
76.5 |
6 |
Behavior Clinician’s
clinical impression |
Yes |
Norway, Sweden,
Great Britain |
Yes |
Mild to moderate |
AE: 42.8% memantine group, 50% placebo group SAE: UK** |
|
Memantine |
2010 |
Emre M, 2010 [38] |
NCT00855686 |
199 |
73 |
6 |
Cognition, Clinician’s clinical impression, Caregiver, Behavior,
Functional autonomy |
Yes |
Europe Australia Turkey |
Yes |
Mild to moderate |
AE (include SAE): 48% memantine group, 43%
placebo group SAE: 15% memantine group, 10% placebo group |
|
Memantine |
2011 |
Ashford JW,
2011 [39] |
NCT00255086 |
13 |
73 |
13 |
Paraclinical variables |
Yes |
United States |
Yes |
Mild to moderate |
UK** |
|
Memantine |
2011 |
Chow TW, 2011
[40] |
NCT00594737 |
16 |
59 |
6 |
Paraclinical variables |
Yes |
Canada |
No |
Mild to moderate |
1 patient with SAE |
|
Memantine |
2011 |
Herrmann N, 2011 [41] |
NCT00401167 |
31 |
89 |
3 |
Clinician’s clinical
impression, Functional autonomy |
No |
Canada |
No |
Moderate to severe
|
AE (include SAE):45% SAE: 9.7% |
|
Memantine |
2011 |
Ondo WG, 2011
[42] |
NCT00646204 |
40 |
69 |
4 |
Clinician’s clinical
impression |
No |
United States |
Yes |
Mild to severe
|
UK** |
|
Memantine |
2011 |
Schulz JB,
2011 [43] |
NCT00624026 |
107 |
74 |
4 |
Cognition |
Yes |
Germany |
No |
Moderate to severe
|
TEAE: 39.2%
|
|
Memantine |
2012 |
Saxton J, 2012 [44] |
NCT00469456 |
255 |
75 |
3 |
Cognition |
Yes |
Australia, United States,
South Africa, New
Zealand |
Yes |
Moderate |
AE: UK** TEAE: 49.6% placcebo group, 48.9% memantine group
SAE: 10% placebo group, 3% memantine group |
|
Memantine |
2012 |
Wilkinson D,
2012 [45] |
NCT00862940 |
278 |
74 |
12 |
Paraclinical variables |
Yes |
Great Britain, Denmark, Netherlands |
Yes |
Moderate |
AE (include SAE): 50% in both group TEAE: 32% memantine group, 22% placebo group SAE: 13% memantune groupe,
14% placebo group |
|
Memantine |
2013 |
Boxer AL,
2013 [46] |
NCT00545974 |
81 |
66 |
6 |
Behavior Clinician’s
clinical impression |
Yes |
United States |
Yes |
Mild to moderate
|
AE: 66.6% placebo group, 71.7% memantine
group SAE: 4.8% placebo group, 2.6% memantine
group |
|
Memantine |
2013 |
Moreau C,
2013 [47] |
NCT01108029 |
25 |
65 |
3 |
Capacity of mobility
measure |
No |
France |
Yes |
Parkinson desease, UPDRS part III item 29
>= 2 |
No adverse events were reported |
|
Memantine |
2013 |
Wang T, 2013
[48] |
NCT00800709 |
22 |
65 |
6 |
Cognition, Paraclinical variables |
No |
China |
Yes |
Moderate to severe
|
UK** |
|
Memantine |
2014 |
Dysken MW, 2014 [49] |
NCT00235716 |
613 |
78 |
12 |
Functional autonomy |
Yes |
United States |
Yes |
Mild to moderate
|
AE (SAE eclude): 59% placebo group, 63% memantine group TEAE: 15.8% placebo group, 18.7% memantine
group SAE: 10% placebo group, 10% memantine group |
|
Memantine Ach |
2012 |
Gordon ML,
2012 [50] |
NCT00551161 |
11 |
76 |
12 |
Paraclinical variables |
No |
United States |
No |
Mild to moderate |
No adverse events were reported |
|
Memantine Donepezil |
2010 |
Modrego PJ, 2010 [51] |
NCT00505167 |
67 |
77 |
6 |
Paraclinical variables |
Yes |
Spain |
No |
Mild to moderate
|
UK** |
|
Memantine Rivastigmine |
2006 |
Dantoine T, 2006 [52] |
NCT00234637 |
202 |
77 |
7 |
Cognition |
Yes |
France |
No |
Moderate to severe
|
AE (SAE exclude): 40.8% SAE: 7% |
|
Memantine Rivastigmine |
2010 |
Olin JT,
20010 [53] |
NCT00305903 |
117 |
78 |
6 |
Adverse drug reactions |
Yes |
United States |
No |
Moderate |
TEAE (SAE exclude): 81.9% SAE: 21.6% |
|
Memantine Rivastigmine |
2011 |
Choi SH, 2011
[54] |
NCT01025466 |
176 |
75 |
4 |
Individual rates having finished trials |
Yes |
Korea |
No |
Moderate |
AE: 53.4% memantine + rivastigmine group,
50.6% rivastigmine group SAE: 4.5% memantine + rivastigmine group,
4.8% rivastigmine group |
|
Rivastigmine |
2008 |
Ballard C,
2008 [55] |
NCT00099216 |
710 |
73 |
6 |
Cognition, Clinician’s clinical impression |
Yes |
Great Britain, United States, Netherlands, Switzerland |
Yes |
Mild to moderate
|
AE (include SAE): 27% rivastigmine group, 5%
placebo group SAE: 15.2 rivastigmine group, 11% placebo
group |
|
Rivastigmine |
2009 |
Sadowsky CH, 2009 [56] |
NCT00428389 |
261 |
77 |
6 |
Individual rates having finished trials |
Yes |
United States |
No |
Mild to moderate
|
AE (include SAE): 31%
TEAE: 13% SAE: 2.3% |
|
Rivastigmine |
2010 |
Farlow MR, 2010 [57] |
NCT00948766 |
713 |
77 |
6 |
Cognition, Functional autonomy |
Yes |
United States |
No |
Severe |
AE (SAE exclude): 59.7% SAE: 21.8% |
|
Rivastigmine |
2011 |
Alva G, 2011 [58] |
NCT00099242 |
800 |
74 |
6 |
Cognition, Clinician’s clinical impression |
Yes |
United States, South America,
Europe, Israel, Korea,
Russian Federation,
Taiwan, |
Yes |
Mild to moderate
|
UK** |
|
Rivastigmine |
2011 |
Articus K, 2011 [59] |
NCT00561392 |
207 |
74 |
6 |
Individual rates having finished trials |
Yes |
Germany |
No |
Mild to moderate
|
AE (include SAE): 59.1% SAE: 8.6% |
|
Rivastigmine |
2011 |
Blesa González R, 2011 [60] |
NCT00549601 |
139 |
77 |
3 |
Adverse drug reactions |
Yes |
Spain |
No |
Mild to moderate |
AE (include SAE): 48.8% to 55.3% depending on rivastigmine group SAE: 2% to 6.4% depending on the rivastigmine
group |
|
Rivastigmine |
2011 |
Nakamura Y, 2011 [61] |
NCT00423085 |
859 |
74 |
6 |
Cognition, Clinician’s clinical impression |
Yes |
Japan |
Yes |
Moderate |
AE (include SAE): 77.6% placebo group, 86.2% rivastigmine
group SAE: 7% placebo group, 5% to 11.6% rivastigmine
group, depending on the rivastigmine dose |
|
Rivastigmine |
2012 |
Cummings J,
2012 [62] |
NCT00506415 |
1584 |
75 |
12 |
Cognition, Functional autonomy |
Yes |
Europe, United States, Canada,
Great Britain |
No |
Mild to moderate
|
AE (include SAE): 68.2% to 75% depending on the rivastigmine
group SAE: 13.3% to 15.7% depending on the rivastigmine
group |
|
Rivastigmine |
2014 |
Aguiar P, 2014 [63] |
NCT01183806 |
40 |
UK** |
6 |
Quality of life |
No |
Brazil |
No |
Mild to moderate
|
UK** |
|
Rivastigmine |
2014 |
Emre M, 2014 [64] |
NCT00623103 |
583 |
72 |
19 |
Adverse drug reactions, Individual rates having finished trials,
Behaviour |
Yes |
Europe, Canada, Turkey,
United States |
No |
Mild to moderate
|
AE (SAE exclude): 74% to 81% depending on the rivastigmine
group SAE: 29% |
*cholinesterase inhibitors
**unknown