Browsing by Author "Umapathi, T."

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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 stroke recovery-extension study (CHIMES-E study): an observational multicenter study to investigate the longer term efficacy of NeuroAiD in stroke recovery
(Karger Publisher, 2013) Venketasubramanian, N.; Young, S.; Tay, S.S.; Chang, H.M.; Umapathi, T.; Chan, B.; de Silva, A.; Wong, L.; Navarro, J.; Zhao, Y.D.; Tan, S.B.; Chen, C.
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, neuro imaging 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.
Effect of Combined Treatment with MLC601 (NeuroAiDTM) and Rehabilitation on Post-Stroke Recovery: The CHIMES and CHIMES-E Studies
(Karger, 2018) Suwanwela, N.C.; Chen, C.L.H.; Lee, C.F.; Young, S.H.; Tay, S.S.; Umapathi, T.; Lao, A.Y.; Gan, H.H.; Baroque li, A.C.; Navarro, J.C.; Chang, H.M.; Advincula, J.M.; Muengtaweepongsa, S.; Chan, B.P.L.; Chua, C.L.; Wijekoon, N.; de Silva, H.A.; Hiyadan, J.H.B.; Wong, K.S.L.; Poungyarin, N.; Eow, G.B; Venketasubramanian, N.; CHIMES-E Study Investigators
BACKGROUND AND PURPOSE: MLC601 has been shown in preclinical studies to enhance neurorestorative mechanisms after stroke. The aim of this post hoc analysis was to assess whether combining MLC601 and rehabilitation has an effect on improving functional outcomes after stroke. METHODS: Data from the CHInese Medicine NeuroAiD Efficacy on Stroke (CHIMES) and CHIMES-Extension (CHIMES-E) studies were analyzed. CHIMES-E was a 24-month follow-up study of subjects included in CHIMES, a multi-centre, double-blind placebo-controlled trial which randomized subjects with acute ischemic stroke, to either MLC601 or placebo for 3 months in addition to standard stroke treatment and rehabilitation. Subjects were stratified according to whether they received or did not receive persistent rehabilitation up to month (M)3 (non- randomized allocation) and by treatment group. The modified Rankin Scale (mRS) and Barthel Index were assessed at month (M) 3, M6, M12, M18, and M24. RESULTS: Of 880 subjects in CHIMES-E, data on rehabilitation at M3 were available in 807 (91.7%, mean age 61.8 ± 11.3 years, 36% female). After adjusting for prognostic factors of poor outcome (age, sex, pre-stroke mRS, baseline National Institute of Health Stroke Scale, and stroke onset-to-study-treatment time), subjects who received persistent rehabilitation showed consistently higher treatment effect in favor of MLC601 for all time points on mRS 0-1 dichotomy analysis (ORs 1.85 at M3, 2.18 at M6, 2.42 at M12, 1.94 at M18, 1.87 at M24), mRS ordinal analysis (ORs 1.37 at M3, 1.40 at M6, 1.53 at M12, 1.50 at M18, 1.38 at M24), and BI ≥95 dichotomy analysis (ORs 1.39 at M3, 1.95 at M6, 1.56 at M12, 1.56 at M18, 1.46 at M24) compared to those who did not receive persistent rehabilitation. CONCLUSIONS: More subjects on MLC601 improved to functional independence compared to placebo among subjects receiving persistent rehabilitation up to M3. The larger treatment effect of MLC601 was sustained over 2 years which supports the hypothesis that MLC601 combined with rehabilitation might have beneficial and sustained effects on neuro-repair processes after stroke. There is a need for more data on the effect of combining rehabilitation programs with stroke recovery treatments.
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.