The value of patient selection in demonstrating treatment effect in stroke recovery trials: lessons from the CHIMES study of MLC601 (NeuroAiD).

Abstract

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.

• Authors: Narayanaswamy Venketasubramanian, Chun Fan Lee, K S Lawrence Wong, Christopher L H Chen
• Journal: Journal of evidence-based medicine (J Evid Based Med) Vol. 8 Issue 3 Pg. 149-53 (Aug 2015) ISSN: 1756-5391 [Electronic] England
• PMID: 26291445 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: © 2015 The Authors Journal of Evidence‐Based Medicine Published by Wiley Publishing Asia Pty Ltd.

Chemical References

• Drugs, Chinese Herbal
• Neuroaid
• Neuroprotective Agents

Topics

• Age Factors
• Brain Ischemia (drug therapy)
• Double-Blind Method
• Drugs, Chinese Herbal (therapeutic use)
• Female
• Humans
• Male
• Neuroprotective Agents (therapeutic use)
• Patient Selection
• Prognosis
• Severity of Illness Index
• Sex Factors
• Stroke (diagnosis, drug therapy)
• Treatment Outcome