title: Prognostic Factors and Pattern of Long-Term Recovery with MLC601 (NeuroAiD™) in the Chinese Medicine NeuroAiD Efficacy on Stroke Recovery - Extension Study.
abstract: The Chinese Medicine NeuroAiD Efficacy on Stroke recovery - Extension (CHIMES-E) study is among the few acute stroke trials with long-term outcome data. We aimed to evaluate the recovery pattern and the influence of prognostic factors on treatment effect of MLC601 over 2 years.
  
  
  
  The CHIMES-E study evaluated the 2 years outcome of subjects aged ≥18 years with acute ischemic stroke, National Institutes of Health Stroke Scale (NIHSS) score 6-14, pre-stroke modified Rankin Scale (mRS) score ≤1 included in a multicenter, randomized, double-blind, placebo-controlled trial of MLC601 for 3 months. Standard stroke care and rehabilitation were allowed during follow-up with mRS score being assessed in-person at month (M) 3 and by telephone at M1, M6, M12, M18 and M24.
  
  
  
  Data from 880 subjects were analyzed. There was no difference in baseline characteristics between treatment groups. The proportion of subjects with mRS score 0-1 increased over time in favor of MLC601 most notably from M3 to M6, thereafter remaining stable up to M24, while the proportion deteriorating to mRS score ≥2 remained low at all time points. Older age (p < 0.01), female sex (p = 0.06), higher baseline NIHSS score (p < 0.01) and longer onset to treatment time (OTT; p < 0.01) were found to be predictors of poorer outcome at M3. Greater treatment effect, with more subjects improving on MLC601 than placebo, was seen among subjects with 2 or more prognostic factors (OR 1.65 at M3, 1.78 at M6, 1.90 at M12, 1.65 at M18, 1.39 at M24), especially in subjects with more severe stroke or longer OTT.
  
  
  
  The sustained benefits of MLC601 over 2 years were due to more subjects improving to functional independence at M6 and beyond compared to placebo. Selection of subjects with poorer prognosis, particularly those with more severe NIHSS score and longer OTT delay, as well as a long follow-up period, may improve the power of future trials investigating the treatment effect of neuroprotective or neurorestorative therapies.
authors.affiliation: Raffles Neuroscience Centre, Singapore, Singapore.
authors.forename: Narayanaswamy
authors.initials: N
authors.lastname: Venketasubramanian
authors.forename: Chun Fan
authors.initials: CF
authors.lastname: Lee
authors.forename: Sherry H
authors.initials: SH
authors.lastname: Young
authors.forename: San San
authors.initials: SS
authors.lastname: Tay
authors.forename: Thirugnanam
authors.initials: T
authors.lastname: Umapathi
authors.forename: Annabelle Y
authors.initials: AY
authors.lastname: Lao
authors.forename: Herminigildo H
authors.initials: HH
authors.lastname: Gan
authors.forename: Alejandro C
authors.initials: AC
authors.lastname: Baroque Ii
authors.forename: Jose C
authors.initials: JC
authors.lastname: Navarro
authors.forename: Hui Meng
authors.initials: HM
authors.lastname: Chang
authors.forename: Joel M
authors.initials: JM
authors.lastname: Advincula
authors.forename: Sombat
authors.initials: S
authors.lastname: Muengtaweepongsa
authors.forename: Bernard P L
authors.initials: BP
authors.lastname: Chan
authors.forename: Carlos L
authors.initials: CL
authors.lastname: Chua
authors.forename: Nirmala
authors.initials: N
authors.lastname: Wijekoon
authors.forename: H Asita
authors.initials: HA
authors.lastname: de Silva
authors.forename: John Harold B
authors.initials: JH
authors.lastname: Hiyadan
authors.forename: Nijasri C
authors.initials: NC
authors.lastname: Suwanwela
authors.forename: K S Lawrence
authors.initials: KS
authors.lastname: Wong
authors.forename: Niphon
authors.initials: N
authors.lastname: Poungvarin
authors.forename: Gaik Bee
authors.initials: GB
authors.lastname: Eow
authors.forename: Christopher L H
authors.initials: CL
authors.lastname: Chen
mesh_terms: D000368:Aged; D001208:Asia; D004185:Disability Evaluation; D004311:Double-Blind Method; D004365:Drugs, Chinese Herbal / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016017:Odds Ratio; D020127:Recovery of Function; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D000071939:Stroke Rehabilitation / Q000009:adverse effects / Q000379:methods*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D004365:Drugs, Chinese Herbal; C546417:Neuroaid; D018696:Neuroprotective Agents