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

• ClinicalTrials.gov Identifier: NCT02975076
• Recruitment Status: Unknown
• First Posted: November 29, 2016
• Last Update Posted: November 29, 2016
• Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
• Information provided by (Responsible Party): Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Stroke, Acute; Ischemic Attack, Transient	Drug: Sanchitongshu; Drug: placebo of Sanchitongshu; Drug: Aspirin; Drug: Clopidogrel; Drug: placebo of clopidogrel	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Radix/Rhizoma Notoginseng Extract (Sanchitongtshu) Plus Asprine for Minor Ischemic Stroke or Transient Ischemic Attack: A Randomized Double-blind Placebo-controlled Study
• Study Start Date: December 2016
• Estimated Primary Completion Date: November 2019
• Estimated Study Completion Date: November 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Sanchitongshu & placebo of lopidogrel; 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	Drug: Sanchitongshu; 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.; Other Name: Radix/Rhizoma Notoginseng extract; Drug: Aspirin; Other Name: Aspirin Enteric-coated Tablets; Drug: placebo of clopidogrel
Placebo Comparator: placebo of Sanchitongshu & lopidogrel; 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	Drug: placebo of Sanchitongshu; The Sanchitongshu placebo capsule contained dark brown muscovado sugar and the same inactive excipient (starch).; Drug: Aspirin; Other Name: Aspirin Enteric-coated Tablets; Drug: Clopidogrel; Other Name: Clopidogrel Bisulfate

Outcome Measures

Primary Outcome Measures :

1. Percentage of patients with the180-day new vascular events, defined as any event of the following: Any stroke (ischemic or hemorrhage) [ Time Frame: 180 days ]

Secondary Outcome Measures :

1. 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 [ Time Frame: 180 days ]
2. Modified Rankin Scale score changes (continuous) and dichotomized at percentage with score 0-2 vs. 3-6 at 180 days follow-up [ Time Frame: 180 days ]
3. Further efficacy exploratory analysis:Impairment (changes in NIHSS scores at 180 days follow-up) [ Time Frame: 180 days ]
4. Further efficacy exploratory analysis:Impairment (changes in Barthel Index at 180 days follow-up) [ Time Frame: 180 days ]
5. Further efficacy exploratory analysis: stroke impact scale [ Time Frame: 180 days ]
6. Efficacy endpoint will also be analyzed stratified by etiological subtypes [ Time Frame: 180 days ]
7. death from any cause [ Time Frame: 180 days ]
8. Severe bleeding incidence (GUSTO definition), including fatal bleeding and symptomatic intracranial hemorrhage. [ Time Frame: 180 days ]
9. Incidence symptomatic and asymptomatic intracranial hemorrhagic events at 180 days [ Time Frame: 180 days ]
10. Incidence Intracranial hemorrhage events at 180 days [ Time Frame: 180 days ]

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. age of 40 years to 80 years
2. diagnosis of an acute minor ischemic stroke or transient ischemic attack; and ability to start the study drug within 24 hours after symptom onset, which was defined as the point at which the patient reported no longer being in a normal condition. Acute minor stroke was defined by a score of 3 or less at the time of randomization on the National Institutes of Health Stroke Scale(NIHSS). TIA was defined as focal brain ischemia with resolution of symptoms within 24 hours after onset plus a moderate-to-high risk of stroke recurrence(defined as a score≥4 at the time of randomization on the ABCD2). All patients were confirmed by brain CT or MRI.
3. Patients had ability to accept the medicine and rules of the research.
4. Patients had no serious complications and had normal renal function and liver function.

Exclusion Criteria:

1. age younger than 40 and older than 80
2. Patients need thrombolysis
3. hemorrhage; other conditions, such as vascular malformation, tumor, abcess, or other major nonischemic brain disease
4. isolated sensory symptoms(e.g., numbness), isolated visual changes, or isolated dizziness or vertigo without evidence of acute infarction on baseline CT or MRI of the head
5. a score of more than 2 on the modified Rankin scale(scores ranges from 0(no symptoms) to 6(death))immediately before the occurrence of the index ischemic stroke or TIA, indicating moderate disability or worse at baseline
6. TIA or minor stroke caused by angiography or surgery
7. a clear indication for anticoagulation therapy(presumed cardiac source of embolus, such as atrial fibrillation or prosthetic cardio valve)
8. anticipated requirement for long-term nonstudy antiplatelet drugs or for non steroidal antiinflammatory drugs affecting platelet function
9. accompanied with severe disorders of heart, liver, and kidney
10. severe noncardiovascular coexisting condition, with a life expectancy of less than 3 months.
11. history of hemorrhage or bleeding tendency of other system( such as thrombocytopenic purpura)
12. gastrointestinal bleeding or major surgery within the previous 3 months
13. planned or probable revascularization(any angioplasty or vascular surgery)within 3 months after.Operation or Interventional Therapy require discontinuation of study drug
14. Aspirin, clopidogrel or notoginseng allergy
15. a history of alcoholism or drug abuse in past 12 months
16. pregnant and lactating women, or women of childbearing age without taking any effective contraceptive measures
17. patients have other serious disease or abnormal laboratory results that is unfavorable to join the research
18. patients receiving other investigational drugs or devices
19. incomprehension of the character and category of the research and unable to follow the research plan

Contacts and Locations

Contacts

Contact: Xiaorong Wang, Master; 13621712767; wangxr_mail@163.com

Contact: Fei Lu; 021-25076146; xinhuakeyan@163.com

Sponsors and Collaborators

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Investigators

• Study Director: Xinhua Hospital; Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine

More Information

• Responsible Party: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
• ClinicalTrials.gov Identifier: NCT02975076 History of Changes
• Other Study ID Numbers: XH-16-037
• First Posted: November 29, 2016
• Last Update Posted: November 29, 2016
• Last Verified: November 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Keywords provided by Xinhua Hospital, Shanghai Jiao Tong University School of Medicine:

Sanchitongshu; Acute Minor Stroke; Transient Ischemic Attack

Additional relevant MeSH terms:

Stroke; Ischemic Attack, Transient; Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Brain Ischemia; Aspirin; Clopidogrel; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists