Safety and efficacy of galantamine (Reminyl) in severe Alzheimer's disease (the SERAD study): a randomised, placebo-controlled, double-blind trial

Summary Background The efficacy of galantamine has been shown in patients with mild, moderate, and advanced moderate Alzheimer's disease (AD). Here we report its efficacy in patients with severe AD. Methods Between December, 2003, and March, 2007, patients aged 84 (SD 6) years with severe AD (mini-mental state examination [MMSE] score 5–12 points), in a nursing home setting were randomly assigned to receive galantamine (n=207), titrated initially to 24 mg/day, or placebo (n=200). Co-primary efficacy measures for cognitive function and ability to undertake normal daily activities were the severe impairment battery (SIB) and the seven-item minimum data set-activities of daily living (MDS-ADL), respectively. Adverse events, vital signs, laboratory parameters, and electrocardiograms were monitored. This trial is registered with ClinicalTrials.gov, number NCT00216593. Findings 168 of 207 (81%) patients in the galantamine group and 161 of 200 (81%) in the placebo group completed the study. Mean SIB scores increased (improved) by 1·9 (95% CI −0·1 to 3·9) points with galantamine and decreased (worsened) by 3·0 (−5·6 to −0·5) points with placebo (between-group least squares mean difference 4·36, 1·3 to 7·5; p=0·006). Mean MDS-ADL self-performance score worsened by 1·2 (0·6 to 1·8) points and 1·6 (0·8 to 2·3) points, respectively (between-group least squares mean difference −0·41, −1·3 to 0·5; p=0·383). Nominally significant between-group differences in favour of galantamine occurred for the SIB domains of memory (p=0·006), praxis (p=0·010), and visuospatial ability (p=0.002), and for the MDS-ADL subitem locomotion on unit (p=0·021). 183 of 207 patients (88%) who received galantamine and 177 of 200 (89%) who received placebo had adverse events, which were mostly mild to moderate. Eight patients (4%) in the galantamine group and 21 patients (11%) in the placebo group died. ECG abnormalities were similar between the two groups. Interpretation Galantamine can be started and used safely in elderly patients with severe AD. Galantamine improved cognitive function but failed to significantly improve the co-primary parameter of overall activities of daily living. Funding Janssen-Cilag EMEA.