Safety and efficacy of pioglitazone for the delay of cognitive impairment in people at risk of Alzheimer's disease (TOMMORROW): a prognostic biomarker study and a phase 3, randomised, double-blind, placebo-controlled trial
RCT (n=3494) terminated early found pioglitazone (0·8mg/d sustained release) did not delay onset of mild cognitive impairment & biomarker algorithm demonstrated 3 times enrichment of events in high vs. low risk placebo group, but did not reach pre-specified significance threshold
Source:
The Lancet Neurology
SPS commentary:
The researcher highlight that because they did not complete the study as planned (terminated Jan 2018, after failing to meet non-futility threshold), the findings can only be considered exploratory.
According to a commentary, although methodological issues might have influenced the negative results, the use of pioglitazone for preventing cognitive decline could also be considered a long shot. On the other hand, the authors provide useful information for future RCTs that aim to delay cognitive decline or clinical onset of Alzheimer's disease, including key points for discussion as enrichment strategies for identification of people at high risk, drug effect expectations, disease progression models, and endpoint selection, and demonstrate the feasibility of these much needed prevention studies.