Synergistic effect of combining MLC601 and rehabilitation on post-stroke recovery: The Chimes-E Study

Abstract

BACKGROUND AND RATIONALE: MLC601 has been shown to enhance natural neuro-repair mechanisms after stroke and may also facilitate rehabilitation-stimulated recovery processes. We aimed to assess the effect of MLC601 and concomitant rehabilitation on stroke recovery in the CHIMES-E study to test the hypotheses that there would be a synergistic effect. METHODS: The CHIMES-E study recruited 880 subjects aged ≥18 years with acute ischemic stroke (AIS), National Institute of Health Stroke Scale (NIHSS) 6–14, and pre-stroke modified Rankin Scale (mRS) ≤1 in a planned double-blind extension study of CHIMES trial with MLC601 or matching placebo given for 3 months in addition to standard stroke care and rehabilitation prescribed by the treating physicians. From Month (M) 3 to M24, mRS was compared between MLC601 and placebo. RESULTS: The study population had a mean age of 61.8 ± 11.3 with 318 (36%) women. Data on rehabilitation and mRS at M3 were available in 807 (91.7%) subjects. Treatment groups were balanced in baseline characteristics except for NIHSS mean score being higher in the rehabilitation group (Rehab) (p = 0.013). Stratification of subjects according to rehabilitation status (Rehab or NoRehab) showed a higher treatment effect of MLC601 on both mRS shift and dichotomy (0–1 vs. 2–6) from M3 to M24 in Rehab group, after adjusting for baseline differences and poorer prognosis factors. In the Rehab group, the adjusted odds of functional independence (mRS of ≤1) increased significantly over time in favor of MLC601 from M3 to M24, with the highest OR at M12 of 2.42 (1.53, 3.81). CONCLUSION: Combining MLC601 and rehabilitation increases improvement of functional recovery over 2 years, supporting a synergistic effect on brain neuro-repair processes after AIS, with more subjects improving to functional independence compared to placebo.