Traditional Chinese Medicine Nonsignificant Effect in Stroke

July 08, 2013

The largest randomized, placebo-controlled clinical trial of traditional medicine in ischemic stroke has shown no statistical difference between the Chinese medicine NeuroAid and placebo in improvement in function.

However, there was a slight trend in favor of the active treatment, which the investigators say justifies further research.

"The absolute benefit of achieving an independent functional outcome (mRS, 0 - 1) was 26 per 1000 patients treated. It is plausible that with a larger study population, such a moderate clinically relevant treatment effect may be detected with statistical significance," they write.

The Chinese Medicine Neuroaid Efficacy on Stroke recovery (CHIMES) study was published online in Stroke on June 18. It was also presented at the recent European Stroke Conference in London.

At the conference, Christopher Chen, FRCP, from the National University of Singapore, explained that in China, there are more than 100 traditional medicines used for ischemic stroke, and there is widespread belief that they have some benefit. It is therefore difficult to conduct placebo-controlled studies there. But outside China, these medicines have limited acceptability, so it is possible to conduct a placebo-controlled trial in other countries.

In the Stroke article, the authors note that pharmacologic studies have demonstrated that some traditional Chinese medicines have antioxidant, anti-inflammatory, vasodilatory, antiplatelet, antiglutamate, and protective effects against ischemia and reperfusion injury. However, meta-analyses of studies in stroke have concluded that the evidence for efficacy and safety is scanty because of the lack of well-designed, randomized, placebo-controlled clinical trials.

Neurorestorative Effects?

NeuroAid (MLC601), a traditional Chinese medicine that combines extracts of 9 herbal and 5 animal components in capsule form, has been shown to restore neurologic and cellular function in animal models of ischemic stroke, Chen reported. Clinical studies in the long-term treatment of stroke patients (2 weeks to 6 months after stroke) showed NeuroAid to be associated with improved recovery in terms of functional outcome and neurologic disability, but these studies were not placebo controlled, he added.

The CHIMES study investigated the use of NeuroAid in acute, moderately severe stroke. Conducted in Southeast Asia (90% of patients were from Singapore/Philippines, with the others from Malaysia and Thailand), the study involved a total of 1100 patients with a National Institute of Health Stroke Scale (NIHSS) score 6 to 14 who were randomly assigned to either active treatment NeuroAid or placebo. The medication was started within 72 hours of stroke onset and was continued for 3 months.

The primary outcome — shift in the modified Rankin scale (mRS) — showed a nonsignificant trend toward benefit in the active-treatment group (odds ratio [OR], 1.09; 95% confidence interval [CI], 0.86 - 1.32).

An mRS score of 0 to 1 at 3 months, a secondary endpoint, showed an OR of 1.11 (95% CI, 0.86 - 1.42) in favor of NeuroAid. The researchers point out that both of these ORs are higher than those in recently completed stroke neuroprotection trials.

No statistical difference was seen for any of the other secondary outcomes, which included NIHSS improvement, difference in NIHSS total and motor scores, Barthel index, and Mini–Mental State Examination scores.

Subgroup analyses showed no statistical heterogeneity for the primary outcome; however, a trend toward benefit in the subgroup receiving treatment beyond 48 hours after stroke onset was noted.

Adverse effects were similar for the 2 groups.

The authors point out that the rate of good outcomes in the CHIMES study was higher than in other recently completed trials, and this has been shown to affect the potential of detecting treatment effects.

They say that the suggestion of a greater effect in patients who are treated beyond 48 hours after stroke onset supports the possible neurorestorative effects of NeuroAid.

Ongoing Extension Study

At the stroke conference, Chen concluded that NeuroAid showed "excellent safety and a nonsignificant efficacy signal." He suggested that 3 months may not be long enough to detect a treatment effect and noted that CHIMES-E, an extension study following up patients from the main CHIMES study for up to 2 years, is now under way. He said he hoped this would "resolve the conflict between uncritical enthusiasm in China and the uninformed skepticism in the West."

NeuroAid is manufactured by Moleac, a company developing new drugs from traditional medicines. This study was funded, in part, by the CHIMES Society, a nonprofit organization to which Moleac (Singapore) contributes, and the National Medical Research Council of Singapore. Christopher Chen received funding from the CHIMES Society for conferences and meetings for presentation of CHIMES data.

Stroke. Published online June 18, 2013. Abstract

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