Comparison of Therapeutic Strategies With Cholinesterase Inhibitors: Stop or Still (SOS) Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 1,205
- 试验地点
- 31
- 主要终点
- The primary outcome is a combination of complete BADL dependency in bathing and dressing and/or institutionalization or death at 2 years after randomization.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •New case of AD referring to a CMRR or MC.
- •Diagnosis of probable or possible AD, defined according to the NINCDS-ARDRA criteria
- •Mild to moderate stage, defined by a MMSE score above 15 at the time of pre-inclusion
- •Patients with indication to CI treatment
- •Patients Naïve to CI treatment
- •Patients aged 50 years or more
- •Menopause or effective contraception (for women)
- •Affiliated person or beneficiary of a social security scheme
- •Patients with AD LTI (Long Term Illeness)
- •Patients agree to participate, with free, informed and written consent signed by the patient and his caregiver
- •Non Inclusion Criteria:
- •Patients diagnosed with Lewy bodies disease, fronto-temporal dementia, or dementia from a cause other than Alzheimer Disease
- •More severe stage of the disease, defined by a MMSE equal or below 15 at the time of inclusion
- •Patients with contraindication to CI treatment
- •Patients residing in an institution at the time of pré-inclusion or randomization
- •Patients with a complete dependency for bathing and dressing at the time of pré-inclusion or randomization ( ADL de Katz, score 2/2 for the item "bathing" and/or "dressing")
- •Patients under tutorship or curatorship, patients unable to express consent
- •Patients with unstable severe general disease compromising the follow-up
- •Patients without caregiver
- •Patients included in another pharmacological trial
- •Pregnant or breastfeeding women
排除标准
- •CI responder patients for whom the MMSE score remained stable or became higher after 6 months of treatment
- •Patients with complete dependency for bathing and dressing at the randomization visit
- •Patients residing in an institution at the randomization visit
研究组 & 干预措施
Group randomized for continuing treatment
Group who continues the cholinesterase inhibitors (CI). The treatment is one of the CI (donepezil, galantamine or rivastigmine) with market authorization and commercialized for more than 15 years in France. The choice of the treatment will be done by the specialist according to his habits; the specialist will monitor the treatment as usual.
All randomised patients will then be followed-up for two years with regular assessment of judgment criteria every 6 months.
干预措施: cholinesterase inhibitors (CI) (donepezil, galantamine or rivastigmine) (Drug)
结局指标
主要结局
The primary outcome is a combination of complete BADL dependency in bathing and dressing and/or institutionalization or death at 2 years after randomization.
时间窗: at 30 months after patient's inclusion
Institutionalization with date of entry will be assessed by specialist at each follow-up time every 6 months. For patients not coming to the memory consultation, caregiver (formal and/or informal) and/or the general practitioner will be systematically contacted to obtain the information. Death and date of death will be assessed by contacting proxy or general practitioner. In case of lack of information the birth City Hall will be contacted to assess the vital status. For dependency in bathing and dressing, although it could be considered as less objective, we choose a level of total dependency, easy to assess with very low risk of misinterpretation.
次要结局
- the number of hospitalizations(at 30 months)
- BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].(at 30 months)
- Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death(at 30 months)
- Institutionalization with date of entry(at 30 months)
- Death and date of death(at 30 months)
- the ADL scale(at 30 months)
- the MMSE score(at 30 months)
- Pharmacologie treatments consumed by the patient(at 30 months)