Browsing by Author "Eow, G.B."

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CHIMES-I: sub-group analyzes of the effects of NeuroAiD according to baseline brain imaging characteristics among patients randomized in the CHIMES study
(Sage Publications, 2013) Navarro, J.C.; Chen, C.L.; Lagamayo, P.D.; Geslani, M.B.; Eow, G.B.; Poungvarin, N.; de Silva, A.; Wong, L.K.; Venketasubramanian, N.; CHIMES Investigators
RATIONALE: The clinical effects of neuroprotective and/or neurorestorative therapies may vary according to location and size of the ischemic injury. Imaging techniques can be useful in stratifying patients for trials that may be beneficial against particular ischemic lesion characteristics. AIM: To test the hypothesis that the efficacy of NeuroAiD compared with placebo in improving functional outcome and reducing neurological deficit in patients with cerebral infarction of intermediate severity varies between sub-groups of patients randomized in the main Chinese Medicine Neuroaid Efficacy on Stroke study when categorized according to baseline imaging characteristics. DESIGN: This is a retrospective cohort sub-group analysis of patients who participated in the main Chinese Medicine Neuroaid Efficacy on Stroke study, a multicenter, double-blind, placebo-controlled trial that recruited 1100 patients within 72 h of ischemic stroke onset with National Institutes of Health Stroke Scale 6-14 and were randomized to either NeuroAiD or placebo taken four capsules three times daily for three months. Review of the baseline images to classify the acute stroke lesions in terms of size, location, and extent of involvement will be performed retrospectively by two readers who will remain blinded as to treatment allocation and outcomes of the subjects. STUDY OUTCOMES: The primary efficacy end-point in the main Chinese Medicine Neuroaid Efficacy on Stroke study is the modified Rankin Scale grades at three-months. Secondary efficacy end-points are the National Institutes of Health Stroke Scale score at three-months; difference of National Institutes of Health Stroke Scale scores between baseline and 10 days and between baseline and three-months; difference of National Institutes of Health Stroke Scale sub-scores between baseline and 10 days and between baseline and three-months; modified Rankin Scale at 10 days, one-month, and three-months; Barthel index at three-months; and Mini Mental State Examination at 10 days and three-months. Analysis of these primary and secondary end-points will be performed for sub-groups defined in this study after review of the baseline brain imaging: nonlacunar and lacunar, cortical and sub-cortical, hemispheric vs. brainstem, Alberta Stroke Program Early CT score <7 and 7-10, and score <8 and 8-10.
Chinese medicine NeuroAiD efficacy on stroke recovery - extension study (CHIMES-E): A multicenter study of long-term efficacy
(Karger Publisher, 2015) Venketasubramanian, N.; Young, S.H.; Tay, S.S.; Umapathi, T.; Lao, A.Y.; Gan, H.H.; Baroque II, A.C.; Navarro, J.C.; Chang, H.M.; Advincula, J.M.; Muengtaweepongsa, S.; Chan, B.P.; Chua, C.L.; Wijekoon, N.; de Silva, H.A.; Hiyadan, J.H.; Suwanwela, N.C.; Wong, K.S.; Poungvarin, N.; Eow, G.B.; Lee, C.F.; Chen, C.L.
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. © 2015 S. Karger AG, Basel.
Chinese medicine neuroaid efficacy on stroke recovery: a double-blind, placebo-controlled, randomized study
(Lippincott Williams and Wilkins, 2013) Chen, C.L.; Young, S.H.; Gan, H.H.; Singh, R.; Lao, A.Y.; Baroque, A.C.; Chang, H.M.; Hiyadan, J.H.; Chua, C.L.; Advincula, J.M.; Muengtaweepongsa, S.; Chan, B.P.; de Silva, H.A.; Towanabut, S.; Suwanwela, N.C.; Poungvarin, N.; Chankrachang, S.; Wong, K.S.; Eow, G.B.; Navarro, J.C.; Venketasubramanian, N.; Lee, C.F.; Bousser, M.G.; CHIMES Study Investigators
BACKGROUND AND PURPOSE: Previous clinical studies suggested benefit for post stroke recovery when MLC601 was administered between 2 weeks and 6 months of stroke onset. The Chinese Medicine Neuroaid Efficacy on Stroke recovery (CHIMES) study tested the hypothesis that MLC601 is superior to placebo in acute, moderately severe ischemic stroke within a 72-hour time window. METHODS: This multicenter, double-blind, placebo-controlled trial randomized 1100 patients with a National Institutes of Health Stroke Scale score 6 to 14, within 72 hours of onset, to trial medications for 3 months. The primary outcome was a shift in the modified Rankin Scale. Secondary outcomes were modified Rankin Scale dichotomy, National Institutes of Health Stroke Scale improvement, difference in National Institutes of Health Stroke Scale total and motor scores, Barthel index, and mini-mental state examination. Planned subgroup analyses were performed according to age, sex, time to first dose, baseline National Institutes of Health Stroke Scale, presence of cortical signs, and antiplatelet use. RESULTS: The modified Rankin Scale shift analysis-adjusted odds ratio was 1.09 (95% confidence interval, 0.86-1.32). Statistical difference was not detected between the treatment groups for any of the secondary outcomes. Subgroup analyses showed no statistical heterogeneity for the primary outcome; however, a trend toward benefit in the subgroup receiving treatment beyond 48 hours from stroke onset was noted. Serious and nonserious adverse events rates were similar between the 2 groups.CONCLUSIONS:MLC601 is statistically no better than placebo in improving outcomes at 3 months when used among patients with acute ischemic stroke of intermediate severity. Longer treatment duration and follow-up of participants with treatment initiated after 48 hours may be considered in future studies. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00554723.
Prognostic factors and pattern of long-term recovery with MLC601 (NeuroAiD™) in the chinese medicine neuroAiD efficacy on stroke recovery - extension study
(Karger, 2017) Venketasubramanian, N.; Lee, C.F.; Young, S.H.; Tay, S.S.; Umapathi, T.; Lao, A.Y.; Gan, H.H.; Chua, C.L.; Wijekoon, N.; de Silva, H.A.; Hiyadan, J.H.; Suwanwela, N.C.; Wong, K.S.; Poungvarin, N.; Eow, G.B.; Chen, C.L.; CHIMES-E Study Investigators
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Synergistic effect of combining MLC601 and rehabilitation on post-stroke recovery: The Chimes-E Study
(Asia Pacific Stroke Organization, Hong Kong Stroke Society and Jiangsu Stroke Association & karger publishing, 2017) Suwanwela, N.; Lee, C.F.; Christopher, L.H.; Chen; Sherry, H.; Young; Tay, S.S.; Umapathi, T.; Lao, A.Y.; Gan, H.H.; Alejandro, C.; Baroque; Jose, C.; Navarro; Hang, H.M.; Joel, M.; Advincula; Muengtaweepongsa, S.; Chan, B.P.L.; Chua, C.L.C.; Wijekoon, N.; de Silva, H.A.; Hiyadan, J.H.B.; Wong, K.S.L.; Poungvarin, N.; Eow, G.B.; Venketasubramanian, N.
BACKGROUND AND RATIONALE: MLC601 has been shown to enhance natural neuro-repair mechanisms after stroke and may also facilitate rehabilitation-stimulated recovery processes. We aimed to assess the effect of MLC601 and concomitant rehabilitation on stroke recovery in the CHIMES-E study to test the hypotheses that there would be a synergistic effect. METHODS: The CHIMES-E study recruited 880 subjects aged ≥18 years with acute ischemic stroke (AIS), National Institute of Health Stroke Scale (NIHSS) 6–14, and pre-stroke modified Rankin Scale (mRS) ≤1 in a planned double-blind extension study of CHIMES trial with MLC601 or matching placebo given for 3 months in addition to standard stroke care and rehabilitation prescribed by the treating physicians. From Month (M) 3 to M24, mRS was compared between MLC601 and placebo. RESULTS: The study population had a mean age of 61.8 ± 11.3 with 318 (36%) women. Data on rehabilitation and mRS at M3 were available in 807 (91.7%) subjects. Treatment groups were balanced in baseline characteristics except for NIHSS mean score being higher in the rehabilitation group (Rehab) (p = 0.013). Stratification of subjects according to rehabilitation status (Rehab or NoRehab) showed a higher treatment effect of MLC601 on both mRS shift and dichotomy (0–1 vs. 2–6) from M3 to M24 in Rehab group, after adjusting for baseline differences and poorer prognosis factors. In the Rehab group, the adjusted odds of functional independence (mRS of ≤1) increased significantly over time in favor of MLC601 from M3 to M24, with the highest OR at M12 of 2.42 (1.53, 3.81). CONCLUSION: Combining MLC601 and rehabilitation increases improvement of functional recovery over 2 years, supporting a synergistic effect on brain neuro-repair processes after AIS, with more subjects improving to functional independence compared to placebo.