The value of patient selection in demonstrating treatment effect in stroke recovery trials: lessons from the CHIMES study of MLC601 (NeuroAiD).
OBJECTIVE
The CHIMES Study compared MLC601 to placebo in patients with ischemic stroke of intermediate severity in the preceding 72 hours. We aimed to verify if patient selection based on two prognostic factors (ie, stroke severity and time to treatment) improves detection of a treatment effect with MLC601.


METHODS
Analyses were performed using data from the CHIMES Study, an international, randomized, placebo-controlled, double-blind trial comparing MLC601 to placebo in patients with ischemic stroke of intermediate severity in the preceding 72 hours. Three subgroups, that is, onset to treatment time (OTT) ≥48 hours; baseline National Institute of Health Stroke Scale (NIHSS) ≥10; both OTT ≥48 hours and baseline NIHSS ≥10, were analyzed using modified Rankin Scale (mRS) ≤1 and a composite endpoint of mRS ≤1, Barthel Index ≥95, and NIHSS ≤1 at month 3.


RESULTS
Placebo response rates were lower (ie, worse natural outcome) among subgroups with prognostic factors. Conversely, MLC601 treatment effects were significantly higher in the subgroups with prognostic factors than for the entire cohort, being highest among patients with both OTT ≥48 hours and baseline NIHSS of 10 to 14: odds ratios of 2.18 (95% CI 1.02 to 4.65) for month 3 mRS ≤1 and 3.88 (95% CI 1.03 to 14.71) for the composite endpoint.


CONCLUSIONS
Patients who have moderately severe strokes and longer OTT demonstrate better treatment effects with MLC601. These factors can guide patient selection in future trials.
Raffles Neuroscience Centre, Raffles Hospital, Singapore.
Narayanaswamy
N
Venketasubramanian
Singapore Clinical Research Institute, Singapore.
Chun Fan
CF
Lee
Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
K S Lawrence
KS
Wong
Department of Pharmacology, Clinical Research Centre, National University of Singapore, Singapore.
Christopher L H
CL
Chen
D000367:Age Factors; D002545:Brain Ischemia / Q000188:drug therapy; D004311:Double-Blind Method; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018579:Patient Selection; D011379:Prognosis; D012720:Severity of Illness Index; D012737:Sex Factors; D020521:Stroke / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome
D004365:Drugs, Chinese Herbal; C546417:Neuroaid; D018696:Neuroprotective Agents
Acute stroke; NeuroAiD; clinical trial; number‐needed‐to‐treat; stroke recovery