CHInese Medicine NeuroAiD Efficacy on Stroke Recovery - Extension Study (CHIMES-E): A Multicenter Study of Long-Term Efficacy.
BACKGROUND
The CHInese Medicine NeuroAiD Efficacy on Stroke recovery (CHIMES) study was an international randomized double-blind placebo-controlled trial of MLC601 (NeuroAiD) in subjects with cerebral infarction of intermediate severity within 72 h. CHIMES-E (Extension) aimed at evaluating the effects of the initial 3-month treatment with MLC601 on long-term outcome for up to 2 years.


METHODS
All subjects randomized in CHIMES were eligible for CHIMES-E. Inclusion criteria for CHIMES were age ≥18, baseline National Institute of Health Stroke Scale of 6-14, and pre-stroke modified Rankin Scale (mRS) ≤1. Initial CHIMES treatment allocation blinding was maintained, although no further study treatment was provided in CHIMES-E. Subjects received standard care and rehabilitation as prescribed by the treating physician. mRS, Barthel Index (BI), and occurrence of medical events were ascertained at months 6, 12, 18, and 24. The primary outcome was mRS at 24 months. Secondary outcomes were mRS and BI at other time points.


RESULTS
CHIMES-E included 880 subjects (mean age 61.8 ± 11.3; 36% women). Adjusted OR for mRS ordinal analysis was 1.08 (95% CI 0.85-1.37, p = 0.543) and mRS dichotomy ≤1 was 1.29 (95% CI 0.96-1.74, p = 0.093) at 24 months. However, the treatment effect was significantly in favor of MLC601 for mRS dichotomy ≤1 at 6 months (OR 1.49, 95% CI 1.11-2.01, p = 0.008), 12 months (OR 1.41, 95% CI 1.05-1.90, p = 0.023), and 18 months (OR 1.36, 95% CI 1.01-1.83, p = 0.045), and for BI dichotomy ≥95 at 6 months (OR 1.55, 95% CI 1.14-2.10, p = 0.005) but not at other time points. Subgroup analyses showed no treatment heterogeneity. Rates of death and occurrence of vascular and other medical events were similar between groups.


CONCLUSIONS
While the benefits of a 3-month treatment with MLC601 did not reach statistical significance for the primary endpoint at 2 years, the odds of functional independence defined as mRS ≤1 was significantly increased at 6 months and persisted up to 18 months after a stroke.
Raffles Neuroscience Centre, Raffles Hospital, Singapore, Singapore.
Narayanaswamy
N
Venketasubramanian
Sherry H
SH
Young
San San
SS
Tay
Thirugnanam
T
Umapathi
Annabelle Y
AY
Lao
Herminigildo H
HH
Gan
Alejandro C
AC
Baroque
Jose C
JC
Navarro
Hui Meng
HM
Chang
Joel M
JM
Advincula
Sombat
S
Muengtaweepongsa
Bernard P L
BP
Chan
Carlos L
CL
Chua
Nirmala
N
Wijekoon
H Asita
HA
de Silva
John Harold B
JH
Hiyadan
Nijasri C
NC
Suwanwela
K S Lawrence
KS
Wong
Niphon
N
Poungvarin
Gaik Bee
GB
Eow
Chun Fan
CF
Lee
Christopher L H
CL
Chen
D000328:Adult; D000368:Aged; D002545:Brain Ischemia / Q000188:drug therapy*; D003103:Coloboma / Q000188:drug therapy; D004311:Double-Blind Method; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005260:Female; D006314:Hearing Loss, Conductive / Q000188:drug therapy; D006330:Heart Defects, Congenital / Q000188:drug therapy; D006801:Humans; D007057:Ichthyosis / Q000188:drug therapy; D008607:Intellectual Disability / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D020752:Neurocutaneous Syndromes / Q000188:drug therapy; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020127:Recovery of Function / Q000187:drug effects*; D020521:Stroke / Q000150:complications / Q000188:drug therapy*; D013995:Time; D016896:Treatment Outcome
D004365:Drugs, Chinese Herbal; C546417:Neuroaid; D018696:Neuroprotective Agents