Comparison of Therapeutic Strategies With Cholinesterase Inhibitors (SOS TRIAL)
Status:
Unknown status
Trial end date:
2021-09-15
Target enrollment:
Participant gender:
Summary
Cholinesterase inhibitors (CI) remain the only drugs with a recognized efficacy in mild to
moderate Alzheimer's disease (AD) in spite of enormous research efforts. However, these drugs
presented as "symptomatic treatment" of AD are considered as having only a weak effect on the
course of AD. The reimbursement of these drugs is regularly challenged due to the lack of
evidence for the impact of these drugs on milestones stages of AD evolution (survival without
severe dementia, restriction in Basic Activities of Daily Living - BADL) and on major
consequences in public health (hospitalization and institutionalization). The great majority
of previous randomized controlled trials conducted with CI have had a too short duration and
the end points were limited to cognition (ADAS Cog scale), IADL (Instrumental Activities of
Daily Living) function and Global Impression of Change. New evidences from the DOMINO trial
(1) conducted in UK, independently of the pharmaceutical industry, showed that the true
effect of CI might be more to avoid or to delay the cognitive or functional decline in AD
than to improve patients; the institutionalisation (2) was also delayed. However, this trial
was conducted in patients with moderate to severe AD, and the interest of the drugs at the
mild to moderate stage remains questionable.
The investigators have shown that a good surrogate marker of survival without severe dementia
would be an increase of ADAS Cog scale of more than six points (3). A post hoc reanalysis of
the pivotal RCT with two CI showed that in mild to moderate patients, CI was associated with
a 15% decrease of patients with a deterioration of ADAS-Cog of more than six points in six
months. Thus at the beginning of dementia the real effect of CI might be more of delaying the
cognitive and functional decline, than to improve the patients. The main objective of the SOS
trial is to demonstrate that the benefit of CI at the early phase of dementia is the same as
at the later phase.