Prognostic Factors and Treatment Effect in the CHIMES Study

Chankrachang, Siwaporn; Navarro, Jose C.; Silva, Deidre Anne De; Towanabut, Somchai; Chúa, Carlos; Lee, Chun Fan; Venketasubramanian, Narayanaswamy; Wong, Ka Sing; Bousser, Marie‐Germaine; Chen, Christopher; Investigators, Chimes Study

doi:10.1016/j.jstrokecerebrovasdis.2014.11.017

Cited by 19 publications

(18 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, it has also been shown that transition from independence in activities of daily living to dependency between 3 and 12 months after a stroke is not insignificant [26]. A follow-up period of 3 months, as is the case in many acute stroke trials, may be of insufficient duration to demonstrate a treatment effect and may require strict patient selection as we have shown in our cohort [27,28]. Longer assessments after the initial short-course therapy may help in further evaluating stroke treatments, such as those using neuroprotectants, previously thought to be ineffective.…”

Section: Discussionmentioning

confidence: 84%

CHInese Medicine NeuroAiD Efficacy on Stroke Recovery - Extension Study (CHIMES-E): A Multicenter Study of Long-Term Efficacy

et al. 2015

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 84%

CHInese Medicine NeuroAiD Efficacy on Stroke Recovery - Extension Study (CHIMES-E): A Multicenter Study of Long-Term Efficacy

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…We have identified several factors that predict poorer outcomes at 3 months, namely older age, female sex, worse baseline stroke severity and longer delay between stroke onset and initiation of treatment [6,8,9,10,15]. The same factors were reported in many in other previous studies [16,17,18,19,20,21,22] and were also found to predict deterioration at 1 and 5 years after a stroke [7,12,22,23,24].…”

Section: Discussionmentioning

confidence: 99%

“…It is thus important to understand the pattern of long-term recovery of subjects with stroke in a neurorestorative trial. In addition, we recently showed in the CHIMES study how predictors of functional outcome, such as age, sex, baseline National Institutes of Health Stroke Scale (NIHSS) score, and treatment delay, affect the ability of demonstrating treatment effect of a therapy for stroke recovery at 3 months [8,9]. …”

Section: Introductionmentioning

confidence: 99%

Prognostic Factors and Pattern of Long-Term Recovery with MLC601 (NeuroAiD™) in the Chinese Medicine NeuroAiD Efficacy on Stroke Recovery - Extension Study

et al. 2016

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Interestingly, in the Philippine cohort of the CHIMES trial, which included more patients with predictors of poorer prognosis, functional and neurological outcomes were improved in favor of MLC601 [15] . Stratification of the entire CHIMES cohort by prognosis also 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 [21] . A recent extension study of the CHIMES trial (CHIMES-E) revealed that a 3-month treatment with MLC601 after stroke improves the functional outcome for up to 2 years among patients with cerebral infarction of intermediate severity [22] .…”

Section: Introductionmentioning

confidence: 91%

MLC901 Favors Angiogenesis and Associated Recovery after Ischemic Stroke in Mice

Gandin

Widmann²,

Lazdunski³

et al. 2016

Cerebrovasc Dis

View full text Add to dashboard Cite

Background: There is increasing evidence that angiogenesis, through new blood vessel formation, results in improved collateral circulation and may impact the long-term recovery of patients. In this study, we first investigated the preventive action of a 5-week pretreatment of MLC901, an herbal extract preparation derived from Chinese medicine, against the deleterious effects of ischemic stroke and its effects on angiogenesis in a model of focal ischemia in mice. Methods: The stroke model was induced by 60 min of middle cerebral artery occlusion followed by reperfusion. MLC901 was administered in the drinking water of animals (6 g/l) for 5 weeks before ischemia and then during reperfusion. Results: MLC901 treatment increased the survival rate, reduced the cerebral infarct area and attenuated the blood brain barrier leakage as well as the neurologic dysfunction following ischemia and reperfusion. We provide evidence that MLC901 enhances endothelial cell proliferation and angiogenesis by increasing the number of neocortical vessels in the infarcted area. MLC901 regulates the expression of hypoxic inducible factor 1α and its downstream targets such as vascular endothelial growth factor and angiopoietins 1 and 2. This work also shows that erythropoietin is an important player in the enhancement of angiogenesis by MLC901. Conclusions: These results demonstrate therapeutic properties of MLC901, in addition to those previously described, in stimulating revascularization, neuroprotection and repair of the neurovascular unit after ischemic stroke.

show abstract

Prognostic Factors and Treatment Effect in the CHIMES Study

Cited by 19 publications

References 26 publications

CHInese Medicine NeuroAiD Efficacy on Stroke Recovery - Extension Study (CHIMES-E): A Multicenter Study of Long-Term Efficacy

CHInese Medicine NeuroAiD Efficacy on Stroke Recovery - Extension Study (CHIMES-E): A Multicenter Study of Long-Term Efficacy

Prognostic Factors and Pattern of Long-Term Recovery with MLC601 (NeuroAiD™) in the Chinese Medicine NeuroAiD Efficacy on Stroke Recovery - Extension Study

MLC901 Favors Angiogenesis and Associated Recovery after Ischemic Stroke in Mice

Contact Info

Product

Resources

About