NCT05321680: WADAD

Withdrawal of Antidementia Drugs in Advanced Dementia (WADAD)

Completed NA Last updated 11 April 2022

What this trial tests

NA trial testing Treatment withdrawal in Dementia in 16 participants. Completed in 20 March 2022.

Timeline

1 March 2021

Primary endpoint
1 December 2021

20 March 2022

Quick facts

Lead sponsor	Centro Hospitalar De São João, E.P.E.
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	treatment
Enrollment	16
Start date	1 March 2021
Primary completion	1 December 2021
Estimated completion	20 March 2022
Sites	1 location across Portugal

Drugs / interventions tested

• Treatment withdrawal — full drug profile →

Conditions studied

• Dementia — all drugs for Dementia →

Sponsor

Centro Hospitalar De São João, E.P.E.

Who can join

Eligibility, any sex, with Dementia. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Dementia is a chronic progressive mental disorder that adversely affects higher cortical functions, including cognition and behavior leading up to disability and dependence in daily life activities. It has become a major public health concern because of its increasing prevalence, chronicity, burden for caregivers, and the high personal and financial costs needed for care. Alzheimer disease (AD) is the most prevalent form of dementia, occurring in 5% to 7% of individuals older than 60. In Portugal, Santana et al study estimated that 160 287 people above 60 years had a diagnosis of dementia in 2013 (prevalence of 5,9%).The increasing national and international prevalence of dementia and its associated burden then imparts a high priority on delivering safe and effective treatment options.

Currently approved treatments available for the symptomatic management of mild to moderate AD include cholinesterase inhibitors (ChEIs) (donepezil, rivastigmine, and galantamine) and a N-methyl- D-aspartate receptor antagonist (memantine). These drugs are also given off-label for other types of dementia (vascular and mixed dementias), with treatment continuing through advanced disease stages. Given that ChEIs have demonstrated short-term modest stabilization on measures of cognition and global functioning in randomized controlled trials (RCTs), several practice guidelines have proposed ChEIs for the treatment of all stages of AD, with some advocating ChEI discontinuation if tolerability issues arise, or if there is no longer a noticeable clinical benefit. Further studies in this setting are important as patients with severe dementia are more functionally impaired, present with comorbid illnesses, posing a higher risk of polypharmacy. In addition, ChEIs have a potential risk of adverse events including nausea, diarrhea, insomnia, vomiting, muscle cramping, fatigue, and weight loss. Less commonly, ChEI might be associated with rhabdomyolysis, convulsions, falls, syncope, pneumonia and death. Because cognitive and behavioral impairments change during the progressive disease course, the effects of medications may be unpredictable, especially over long durations of treatment. It might be challenging to weigh minimally beneficial effects against predicted harms of continued treatment, considering both patient and caregiver-centered care goals besides less clinically relevant cognitive outcomes.

Only a small number of discontinuation RCTs were conducted to date but involved relatively few participants with heterogeneous designs, disease severities and outcomes. As so, clinicians take individualized discontinuation decisions and the only consensual domains are a lack of response and a loss of effectiveness. The present pragmatic clinical trial will compare the efficacy of maintaining pharmacological treatment versus treatment cessation on cognition, behavior, functional disability and quality of life of patients and caregivers, among patients with severe dementia due to AD, with or without small vessel subcortical vascular disease. The investigators will consider other important endpoints besides cognitive functioning including mood, apathy, energy and neuropsychiatric symptoms. Moreover, this trial will try to look for outcomes that engage patients and families in treatment decisions.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.