title: Chinese medicine NeuroAiD efficacy stroke recovery-extension study (CHIMES-E study): an observational multicenter study to investigate the longer-term efficacy of NeuroAiD in stroke recovery.
abstract: BACKGROUND
  Stroke carries a poor long-term prognosis for death and disability. There are few acute treatments that reduce death and disability after stroke. The ongoing international, multicenter, randomized, placebo-controlled, double-blind CHIMES trial is currently testing the hypothesis that a 3-month course of the traditional Chinese medicine MLC601 (NeuroAiD) is superior to placebo in reducing neurological deficit and improving functional outcome after acute ischemic stroke in patients receiving standard stroke care. This extension study tests the hypothesis that at 2 years, an initial 3-month administration of NeuroAiD is superior to placebo in reducing neurological deficit and improving functional outcome in patients with cerebral infarction of an intermediate range of severity.
  
  
  METHODS
  Study subjects will be those who are already participants in CHIMES - aged above 21 years, had signs and symptoms of acute stroke, 6 ≤ NIHSS ≤ 14, neuroimaging consistent with ischemic stroke, and received study medication within 72 h of stroke onset. A subject will not be eligible for inclusion in CHIMES-E if they have withdrawn consent from all participation and follow-up for CHIMES. Subjects will be contacted at 6, 12, 18 and 24 months after CHIMES enrollment. After verbal consent is obtained, subjects will be assessed for functional state by the modified Rankin scale (mRS) and Barthel Index (BI), and a history of recurrent vascular events as well as medical events. The primary outcome measure will be the mRS at month 24. Secondary outcome measures will be mRS and BI at 6, 12 and 18 months, and BI at 24 months. Analysis will be based on the intention-to-treat principle. If the number of patients lost to follow-up is substantial, a sensitivity analysis based on the last observation carried forward method will be carried out, to compare the results with those from the main analysis without imputation. Based on a cumulative odds ratio of 1.5 for the NeuroAiD group, a two-sided test of 5% type I error and an expected 30% dropout rate after 2 years of follow-up for the 1,100 patients recruited into CHIMES, the 770 subjects with mRS data expected to be available at year 2 yields an 89% power to detect a difference in efficacy between NeuroAiD and placebo.
  
  
  CONCLUSIONS
  This study will provide evidence for the longer-term efficacy of an initial course of a neurorestorative therapy after acute ischemic stroke of intermediate severity.
authors.affiliation: Division of Neurology, University Medicine Cluster, National University of Singapore, Singapore, Singapore. drnvramani @ gmail.com
authors.forename: N
authors.initials: N
authors.lastname: Venketasubramanian
authors.forename: Sherry
authors.initials: S
authors.lastname: Young
authors.forename: San San
authors.initials: SS
authors.lastname: Tay
authors.forename: Hui Meng
authors.initials: HM
authors.lastname: Chang
authors.forename: T
authors.initials: T
authors.lastname: Umapathi
authors.forename: Bernard
authors.initials: B
authors.lastname: Chan
authors.forename: Asita
authors.initials: A
authors.lastname: de Silva
authors.forename: Lawrence
authors.initials: L
authors.lastname: Wong
authors.forename: Jose
authors.initials: J
authors.lastname: Navarro
authors.forename: Yu-Dong
authors.initials: YD
authors.lastname: Zhao
authors.forename: Say Beng
authors.initials: SB
authors.lastname: Tan
authors.forename: Christopher
authors.initials: C
authors.lastname: Chen
mesh_terms: D002544:Cerebral Infarction / Q000150:complications / Q000188:drug therapy; D003627:Data Interpretation, Statistical; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D023381:Endpoint Determination; D006801:Humans; D009422:Nervous System Diseases / Q000188:drug therapy / Q000209:etiology; D009460:Neurologic Examination; D016032:Randomized Controlled Trials as Topic; D020127:Recovery of Function / Q000187:drug effects*; D012107:Research Design; D020521:Stroke / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D013689:Telephone; D016896:Treatment Outcome
chemical_list: D004365:Drugs, Chinese Herbal; C546417:Neuroaid