Sample size calculation
The sample size for this trial was estimated on the basis of comparison of neuroEPO plus and placebo with respect to the primary efficacy outcome, the change from baseline at 48 weeks in the ADAS-Cog11 score. A reduction of at least 3 points between the changes of the ADAS-Cog11 total score in the neuroEPO plus vs. the placebo group was hypothesized. Therefore, after assuming 20% discontinuation rate, 80% power to achieve statistical significance at a 2-sided An interim analysis for futility or efficacy was planned, when the first 20 participants of each group were included and evaluated at 24 weeks. At that moment, a blinded readjustment of the sample size based on the observed variance was considered. This adjustment was necessary and the sample size was increased by 60 (20 patients by group). The final sample size was 174 (58 patients by group).Additional information is provided in Methods in 