Sanchitongtshu Plus Asprine for Minor Ischemic Stroke or Transient Ischemic Attack: A Randomized Double-blind Study

Not yet recruiting

Phase N/A Results N/A

Trial Description

Agents of sanchi have been widely used as a complementary medicine for stroke in China. Sanchitongshu is a new Chinese patent medicine extracted from sanchi which has stronger anti-platelet activity than other agents of sanchi. The investigators's aim was to investigate the synergistic action of aspirin combined with sanchitongshu capsule in the treatment of patients with minor ischemic stroke and transient ischemic attack.

Detailed Description

Transient ischemic attack (TIA) and acute minor ischemic stroke are common and often lead to disabling events. In China, there are approximately 3 million new strokes every year, and approximately 30% of them are minor ischemic strokes. The incidence of TIA in China has not been determined, but on the basis of the incidence in other countries, there are probably more than 2 million TIAs annually in China. The risk of another stroke occurring after a TIA or minor stroke is high, with approximately 10 to 20% of patients having a stroke within 3 months after the index event; most of these strokes occur within the first 2 days. The role of antiplatelet therapy for secondary stroke prevention has been well established.
As yet, aspirin is the only antiplatelet agent that has been studied in the acute phase of stroke, during which its benefit is modest. Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial shows that among patients with high-risk TIA or minor ischemic stroke who are initially seen within 24 hours after symptom onset, treatment with clopidogrel plus aspirin for 21 days, followed by clopidogrel alone for a total of 90 days, is superior to aspirin alone in reducing the risk of subsequent stroke events. The combination of clopidogrel with aspirin did not cause more hemorrhagic events in this patient population than aspirin alone. The analytical results provided basis for the synergistical effect of Aspirin and clopidogrel in inhibiting platelet aggregation. However, long term use of clopidogrel bring people financial burden so that the patients have less compliance of medication. Therefore, the investigators need to explore new treatment for more effective, safe and economic.
Sanchi is one of the most widely used herbal medicine in China for ischemic stroke, of which panax notoginseng saponins (PNS) are the main active components. Previously there were lots of clinical trials on agents of PNS for ischemic stroke in China and had positive results. Sanchitongshu capsule is a new Chinese patent medicine extracted from sanchi. 80% of the ingredients in sanchi-tongshu capsule are panaxatriol saponins (PTS) and 60% of PTS are Rg1 which has strongest anti-platelet activity of all the PNS. PTS were proven by experiment and phase III clinical trials to have antithrombosis effect through mechanisms of inhibiting platelet aggregation, decreasing blood viscosity, strengthening activities of fibrinolysis system, and promoting vascular endothelial NO releasing. More recent experimental studies indicated anti-inflammatory and neuroprotective effect of PTS. Compared with other agents of Sanchi, Sanchitongshu capsule contains higher purity of PTS and Rg1. Thus, Sanchitongshu capsule theoretically should be vigorous in improving ischemic status after ischemic stroke.
Include, the investigators will investigate the synergistic action of aspirin combined with sanchitongshu capsule in the treatment of patients with minor ischemic stroke and transient ischemic attack.

Conditions

Interventions

  • Clopidogrel (Plavix┬«)Drug
    Other Names: Plavix
    ARM 1: Kind: Experimental
    Label: placebo of Sanchitongshu & lopidogrel
    Description: placebo of sanchitongshu1 capsule each time ,three times a day and Aspirin 75mg for 90 days;clopidogrel 75mg per day for 21 days after randomization
  • Aspirin Drug
    Other Names: clopidogrel; combination aspirin-dipyridamole
    ARM 1: Kind: Experimental
    Label: Sanchitongshu & placebo of lopidogrel
    Description: sanchitongshu 1 capsule each time ,three times a day and Aspirin 75mg for 90 days ; placebo of clopidogrel 75mg daily for 21 days after randomization
    ARM 2: Kind: Experimental
    Label: placebo of Sanchitongshu & lopidogrel
    Description: placebo of sanchitongshu1 capsule each time ,three times a day and Aspirin 75mg for 90 days;clopidogrel 75mg per day for 21 days after randomization
  • Sanchitongshu Drug
    Other Names: Radix/Rhizoma Notoginseng extract
    Intervention Desc: The study drugs were manufactured according to Good Manufacturing Practice (GMP) by the Pharmaceutical Factory of Chengdu Huasun Group Inc. Ltd. and presented in the form capsules. Every Sanchitongshu capsule weighed 200 mg, contained 100 mg of panaxatriol saponin (PTS) and 100 mg inactive excipient (starch). PTS comprised of dried extracts from roots of Radix Notoginseng, and had been standardised with respect to Ginsenoside Rg1 (50%), Ginsenoside Re (6%), Notoginsenoside R1 (11%). The amounts of the active ingredients were determined by analytical RP-HPLC using an acetonitrile-water gradient system as mobile hase. The peaks were detected by UV-DAD.
    ARM 1: Kind: Experimental
    Label: Sanchitongshu & placebo of lopidogrel
    Description: sanchitongshu 1 capsule each time ,three times a day and Aspirin 75mg for 90 days ; placebo of clopidogrel 75mg daily for 21 days after randomization
  • Placebo of Sanchitongshu Drug
    Intervention Desc: The Sanchitongshu placebo capsule contained dark brown muscovado sugar and the same inactive excipient (starch).
    ARM 1: Kind: Experimental
    Label: placebo of Sanchitongshu & lopidogrel
    Description: placebo of sanchitongshu1 capsule each time ,three times a day and Aspirin 75mg for 90 days;clopidogrel 75mg per day for 21 days after randomization
  • Placebo of clopidogrel Drug
    ARM 1: Kind: Experimental
    Label: Sanchitongshu & placebo of lopidogrel
    Description: sanchitongshu 1 capsule each time ,three times a day and Aspirin 75mg for 90 days ; placebo of clopidogrel 75mg daily for 21 days after randomization

Outcomes

Type Measure Time Frame Safety Issue
Primary Percentage of patients with the180-day new vascular events, defined as any event of the following: Any stroke (ischemic or hemorrhage) 180 days
Secondary Percentage of patients with the 180-day new clinical vascular events (ischemic stroke/ hemorrhagic stroke/ TIA/ MI/ vascular death) as a cluster and evaluated individually 180 days
Secondary Modified Rankin Scale score changes (continuous) and dichotomized at percentage with score 0-2 vs. 3-6 at 180 days follow-up 180 days
Secondary Further efficacy exploratory analysis:Impairment (changes in NIHSS scores at 180 days follow-up) 180 days
Secondary Further efficacy exploratory analysis:Impairment (changes in Barthel Index at 180 days follow-up) 180 days
Secondary Further efficacy exploratory analysis: stroke impact scale 180 days
Secondary Efficacy endpoint will also be analyzed stratified by etiological subtypes 180 days
Secondary death from any cause 180 days
Secondary Severe bleeding incidence (GUSTO definition), including fatal bleeding and symptomatic intracranial hemorrhage. 180 days
Secondary Incidence symptomatic and asymptomatic intracranial hemorrhagic events at 180 days 180 days
Secondary Incidence Intracranial hemorrhage events at 180 days 180 days

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