Siwaporn Chankrachang1, Jose C Navarro2, Deidre A de Silva3, Somchai Towanabut4, Carlos L Chua5, Chun Fan Lee6, Narayanaswamy Venketasubramanian7, K S Lawrence Wong8, Marie-Germaine Bousser9, Christopher L H Chen10. 1. Chiang Mai University, Amphur Muang, Chiang Mai, Thailand. 2. University of Santo Tomas Hospital, España Boulevard, Manila, Philippines. 3. National Neuroscience Institute-Singapore General Hospital Campus, Singapore General Hospital, Singapore. 4. Prasat Neurological Institute, Rajthevi, Bangkok, Thailand. 5. Philippine General Hospital, University of the Philippines Manila, Manila, Philippines. 6. Singapore Clinical Research Institute, Singapore. 7. Raffles Neuroscience Centre, Raffles Hospital, Singapore. 8. Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China. 9. Lariboisière University Hospital, Paris, France. 10. Department of Pharmacology, National University of Singapore, Clinical Research Centre, Singapore. Electronic address: phccclh@nus.edu.sg.
Abstract
BACKGROUND: Stroke trials often analyze patients with heterogeneous prognoses using a single definition of outcome, which may not be applicable to all subgroups. We aimed to evaluate the treatment effects of MCL601 among patients stratified by prognosis in the Chinese Medicine Neuroaid Efficacy on Stroke Recovery (CHIMES) study. METHODS: Analyses were performed using data from the CHIMES study, an international, randomized, placebo-controlled, double-blind trial comparing MLC601 with placebo in patients with ischemic stroke of intermediate severity in the preceding 72 hours. All subjects with baseline data and the modified Rankin Scale (mRS) score at 3 months were included. RESULTS: Data from 1006 subjects were analyzed. The predictive variables for mRS score greater than 1 at month 3 were age older than 60 years (P < .001), baseline National Institutes of Health Stroke Scale score 10-14 (P < .001), stroke onset to initiation of study treatment of more than 48 hours (P < .001), and female sex (P = .026). A higher number of predictors was associated with poorer mRS score at month 3 for both placebo (P < .001) and treatment (P < .001) groups. The odds ratio (OR) for achieving a good outcome increased with the number of predictors and reached statistical significance in favor of MLC601 among patients with 2 to 4 predictors combined (unadjusted OR = 1.44, 95% confidence interval, 1.02-2.03; adjusted OR = 1.60, 95% confidence interval, 1.10-2.34). CONCLUSIONS: Age, sex, baseline National Institutes of Health Stroke Scale score, and time to first dose are predictors of functional outcome in the CHIMES study. Stratification by prognosis showed that patients with 2 or more predictors of poorer outcome have better treatment effect with MLC601 than patients with single or no prognostic factor. These results have implications on designing future stroke trials.
RCT Entities:
BACKGROUND:Stroke trials often analyze patients with heterogeneous prognoses using a single definition of outcome, which may not be applicable to all subgroups. We aimed to evaluate the treatment effects of MCL601 among patients stratified by prognosis in the Chinese Medicine Neuroaid Efficacy on Stroke Recovery (CHIMES) study. METHODS: Analyses were performed using data from the CHIMES study, an international, randomized, placebo-controlled, double-blind trial comparing MLC601 with placebo in patients with ischemic stroke of intermediate severity in the preceding 72 hours. All subjects with baseline data and the modified Rankin Scale (mRS) score at 3 months were included. RESULTS: Data from 1006 subjects were analyzed. The predictive variables for mRS score greater than 1 at month 3 were age older than 60 years (P < .001), baseline National Institutes of Health Stroke Scale score 10-14 (P < .001), stroke onset to initiation of study treatment of more than 48 hours (P < .001), and female sex (P = .026). A higher number of predictors was associated with poorer mRS score at month 3 for both placebo (P < .001) and treatment (P < .001) groups. The odds ratio (OR) for achieving a good outcome increased with the number of predictors and reached statistical significance in favor of MLC601 among patients with 2 to 4 predictors combined (unadjusted OR = 1.44, 95% confidence interval, 1.02-2.03; adjusted OR = 1.60, 95% confidence interval, 1.10-2.34). CONCLUSIONS: Age, sex, baseline National Institutes of Health Stroke Scale score, and time to first dose are predictors of functional outcome in the CHIMES study. Stratification by prognosis showed that patients with 2 or more predictors of poorer outcome have better treatment effect with MLC601 than patients with single or no prognostic factor. These results have implications on designing future stroke trials.
Authors: Narayanaswamy Venketasubramanian; Chun Fan Lee; Sherry H Young; San San Tay; Thirugnanam Umapathi; Annabelle Y Lao; Herminigildo H Gan; Alejandro C Baroque Ii; Jose C Navarro; Hui Meng Chang; Joel M Advincula; Sombat Muengtaweepongsa; Bernard P L Chan; Carlos L Chua; Nirmala Wijekoon; H Asita de Silva; John Harold B Hiyadan; Nijasri C Suwanwela; K S Lawrence Wong; Niphon Poungvarin; Gaik Bee Eow; Christopher L H Chen Journal: Cerebrovasc Dis Date: 2016-11-15 Impact factor: 2.762
Authors: Nijasri C Suwanwela; Christopher L H Chen; Chun Fan Lee; Sherry H Young; San San Tay; Thirugnanam Umapathi; Annabelle Y Lao; Herminigildo H Gan; Alejandro C Baroque Ii; Jose C Navarro; Hui Meng Chang; Joel M Advincula; Sombat Muengtaweepongsa; Bernard P L Chan; Carlos L Chua; Nirmala Wijekoon; H Asita de Silva; John Harold B Hiyadan; Ka Sing Lawrence Wong; Niphon Poungvarin; Gaik Bee Eow; Narayanaswamy Venketasubramanian Journal: Cerebrovasc Dis Date: 2018-09-05 Impact factor: 2.762
Authors: Ramesh Kumar; Ohnmar Htwe; Azmi Baharudin; Mohammad Hisam Ariffin; Shaharuddin Abdul Rhani; Kamalnizat Ibrahim; Aishah Rustam; Robert Gan Journal: JMIR Res Protoc Date: 2016-12-05