Continuation versus discontinuation of treatment for severe dementia: randomized, pragmatic, open-label, clinical trial to evaluate the efficacy of continuing drug treatment in patients with severe dementia (STOP-DEM).

Background: Previous observational studies and clinical trials have shown that cholinesterase inhibitors (with or without memantine) provide benefit for patients with mild-to-moderate Alzheimer's disease. However, the impact of treatment continuation after progression to severe disease is unknown. The main aim of this study is to evaluate the effect and safety of continuing treatment with ChEIs (with or without memantine) for patients with severe dementia.

Methods: This randomized, pragmatic, open-label clinical trial with blinded evaluators will evaluate the efficacy of continuing drug treatment in patients with advanced dementia. A total of 302 community-dwelling patients with severe dementia, Alzheimer's disease, with or without a coexisting diagnosis of vascular dementia, and a score of 10 or less on the Mini-Mental State Examination who received previous treatment with a cholinesterase inhibitor (with or without memantine) for at least 3 months, will be randomized to continue or discontinue drug treatment. Follow-up will be 12 months or until the primary endpoint is achieved. The primary endpoint is entry into institutional care and progression of disability, defined as a loss of 2 of 4 basic functions, or 6 of 11 instrumental functions, according to the Bristol Activities of Daily Living Scale at 12 months. The secondary outcomes are patient changes in functional and cognitive state, quality of life, and caregiver burden.

Discussion: We expect that the results of our study will allow to identify if there is clinical relevant impact for patients and caregivers between maintaining or halting pharmacological treatment.

Trial Registration: The study was prospectively registered in the REec (2017-000042-22) on May 11 2017 and ID ISRCTN12134230 on February 25 2019.