A 24‐Week, Randomized, Controlled Trial of Rivastigmine Patch 13.3 mg/24 h Versus 4.6 mg/24 h in Severe Alzheimer's Dementia

AIMS: The 24‐week, prospective, randomized, double‐blind ACTION study investigated the efficacy, safety, and tolerability of 13.3 versus 4.6 mg/24 h rivastigmine patch in patients with severe Alzheimer's disease (AD). METHODS: Patients had probable AD and Mini–Mental State Examination scores ≥3–≤12. Primary outcome measures were as follows: Severe Impairment Battery (SIB) and AD Cooperative Study–Activities of Daily Living scale–Severe Impairment Version (ADCS‐ADL‐SIV). Secondary outcomes were as follows: ADCS‐Clinical Global Impression of Change (ADCS‐CGIC), 12‐item Neuropsychiatric Inventory (NPI‐12), and safety/tolerability. RESULTS: Of 1014 patients screened, 716 were randomized to 13.3 mg/24 h (N = 356) or 4.6 mg/24 h (N = 360) patch. Baseline characteristics/demographics were comparable. Completion rates were as follows: 64.3% (N = 229) with 13.3 mg/24 h and 65.0% (N = 234) with 4.6 mg/24 h patch. The 13.3 mg/24 h patch was significantly superior to 4.6 mg/24 h patch on cognition (SIB) and function (ADCS‐ADL‐SIV) at Week 16 (P < 0.0001 and P = 0.049, respectively) and 24 (primary endpoint; P < 0.0001 and P = 0.025). Significant between‐group differences (Week 24) were observed on the ADCS‐CGIC (P = 0.0023), not NPI‐12 (P = 0.1437). A similar proportion of the 13.3 mg/24 h and 4.6 mg/24 h patch groups reported adverse events (AEs; 74.6% and 73.3%, respectively) and serious AEs (14.9% and 13.6%). CONCLUSIONS: The 13.3 mg/24 h patch demonstrated superior efficacy to 4.6 mg/24 h patch on SIB and ADCS‐ADL‐SIV, without marked increase in AEs, suggesting higher‐dose patch has a favorable benefit‐to‐risk profile in severe AD.