Prognostic factors and treatment effect in the CHIMES study

© 2015 by National Stroke Association. Background: Stroke trials often analyze patients with heterogeneous prognoses using a single definition of outcome, which may not be applicable to all subgroups. We aimed to evaluate the treatment effects of MCL601 among patients stratified by prognosis in the Chinese Medicine Neuroaid Efficacy on Stroke Recovery (CHIMES) study. Methods: Analyses were performed using data from the CHIMES study, an international, randomized, placebo-controlled, double-blind trial comparing MLC601 with placebo in patients with ischemic stroke of intermediate severity in the preceding 72 hours. All subjects with baseline data and the modified Rankin Scale (mRS) score at 3 months were included. Results: Data from 1006 subjects were analyzed. The predictive variables for mRS score greater than 1 at month 3 were age older than 60 years (P <.001), baseline National Institutes of Health Stroke Scale score 10-14 (P <.001), stroke onset to initiation of study treatment of more than 48 hours (P <.001), and female sex (P =.026). A higher number of predictors was associated with poorer mRS score at month 3 for both placebo (P <.001) and treatment (P =.001) groups. The odds ratio (OR) for achieving a good outcome increased with the number of predictors and reached statistical significance in favor of MLC601 among patients with 2 to 4 predictors combined (unadjusted OR = 1.44, 95% confidence interval, 1.02-2.03; adjusted OR = 1.60, 95% confidence interval, 1.10-2.34). Conclusions: Age, sex, baseline National Institutes of Health Stroke Scale score, and time to first dose are predictors of functional outcome in the CHIMES study. Stratification by prognosis showed that patients with 2 or more predictors of poorer outcome have better treatment effect with MLC601 than patients with single or no prognostic factor. These results have implications on designing future stroke trials.Link_to_subscribed_fulltex

Migraine disability awareness campaign in Asia: Migraine assessment for prophylaxis: Research submission

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Good clinical practice points on the use of acetylcholinesterase inhibitors in myasthenia gravis: recommendation from a South-East Asian regional special interest group on myasthenia gravis

Conference Theme: Innovation in Neurolog

Chinese medicine neuroaid efficacy on stroke recovery: A double-blind, placebo-controlled, randomized study

BACKGROUND AND PURPOSE-: Previous clinical studies suggested benefit for poststroke recovery when MLC601 was administered between 2 weeks and 6 months of stroke onset. The Chinese Medicine Neuroaid Efficacy on Stroke recovery (CHIMES) study tested the hypothesis that MLC601 is superior to placebo in acute, moderately severe ischemic stroke within a 72-hour time window. METHODS-: This multicenter, double-blind, placebo-controlled trial randomized 1100 patients with a National Institutes of Health Stroke Scale score 6 to 14, within 72 hours of onset, to trial medications for 3 months. The primary outcome was a shift in the modified Rankin Scale. Secondary outcomes were modified Rankin Scale dichotomy, National Institutes of Health Stroke Scale improvement, difference in National Institutes of Health Stroke Scale total and motor scores, Barthel index, and mini-mental state examination. Planned subgroup analyses were performed according to age, sex, time to first dose, baseline National Institutes of Health Stroke Scale, presence of cortical signs, and antiplatelet use. RESULTS-: The modified Rankin Scale shift analysis-adjusted odds ratio was 1.09 (95% confidence interval, 0.86-1.32). Statistical difference was not detected between the treatment groups for any of the secondary outcomes. Subgroup analyses showed no statistical heterogeneity for the primary outcome; however, a trend toward benefit in the subgroup receiving treatment beyond 48 hours from stroke onset was noted. Serious and nonserious adverse events rates were similar between the 2 groups. CONCLUSIONS-: MLC601 is statistically no better than placebo in improving outcomes at 3 months when used among patients with acute ischemic stroke of intermediate severity. Longer treatment duration and follow-up of participants with treatment initiated after 48 hours may be considered in future studies. © 2013 American Heart Association, Inc.Link_to_subscribed_fulltex

Baseline characteristics and treatment response of patients from the Philippines in the CHIMES study

© 2014 The Authors. Background: The CHIMES Study compared MLC601 with placebo in patients with ischemic stroke of intermediate severity in the preceding 72h. Sites from the Philippines randomized 504 of 1099 (46%) patients in the study. We aimed to define the patient characteristics and treatment responses in this subgroup to better plan future trials. Methods: The CHIMES dataset was used to compare the baseline characteristics, time from stroke onset to study treatment initiation, and treatment responses to MLC601 between patients recruited from Philippines and the rest of the cohort. Treatment effect was analyzed using end-points at month 3 as described in the primary publication, that is, modified Rankin Score, National Institutes of Health Stroke Scale, and Barthel Index. Results: The Philippine cohort was younger, had more women, worse baseline National Institutes of Health Stroke Scale, and longer time delay from stroke onset to study treatment compared with the rest of the cohort. Age (P=0·003), baseline National Institutes of Health Stroke Scale (P<0·001), and stroke onset to study treatment initiation (P=0·016) were predictors of modified Rankin Score at three-months. Primary analysis of modified Rankin Score shift was in favor of MLC601 (adjusted odds ratio 1·41, 95% confidence interval 1·01-1·96). Secondary analyses were likewise in favor of MLC601 for modified Rankin Score dichotomy 0-1, improvement in National Institutes of Health Stroke Scale (total and motor scores), and Barthel Index. Conclusions: The treatment effects in the Philippine cohort were in favor of MLC601. This may be due to inclusion of more patients with predictors of poorer outcome.Link_to_subscribed_fulltex

Effects of MLC601 on early vascular events in patients after stroke: The CHIMES study

BACKGROUND AND PURPOSE - Early vascular events are an important cause of morbidity and mortality in the first 3 months after a stroke. We aimed to investigate the effects of MLC601 on the occurrence of early vascular events within 3 months of stroke onset. METHODS - Post hoc analysis was performed on data from subjects included in the CHInese Medicine Neuroaid Efficacy on Stroke recovery (CHIMES) study, a randomized, placebo-controlled, double-blinded trial that compared MLC601 with placebo in 1099 subjects with ischemic stroke of intermediate severity in the preceding 72 hours. Early vascular events were defined as a composite of recurrent stroke, acute coronary syndrome, and vascular death occurring within 3 months of stroke onset. RESULTS - The frequency of early vascular events during the 3-month follow-up was significantly less in the MLC601 group than in the placebo group (16 [2.9%] versus 31 events [5.6%]; risk difference=-2.7%; 95% confidence interval, -5.1% to -0.4%; P=0.025) without an increase in nonvascular deaths. Kaplan-Meier survival analysis showed a difference in the risk of vascular outcomes between the 2 groups as early as the first month after stroke (Log-rank P=0.024; hazard ratio, 0.51; 95% confidence interval, 0.28-0.93). CONCLUSIONS - Treatment with MLC601 was associated with reduced early vascular events among subjects in the CHIMES study. The mechanisms for this effect require further study. © 2013 American Heart Association, Inc.Link_to_subscribed_fulltex