Clinical trial NCT03661411: Antiplatelet vs R-tPA for Acute Mild Ischemic Stroke
Official title: Antiplatelet vs R-tPA for Acute Mild Ischemic Stroke: a Prospective, Random, Blinded Assessment of Outcome and Open Label Multi-center Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Stroke
Lead sponsor: General Hospital of Shenyang Military Region
Sponsor class: OTHER
First posted: 2018-09-07
Enrollment: 760
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Acute ischemic stroke (AIS) is one of common diseases with significant morbidity, mortality and disability. A wide array of studies confirms that intravenous thrombolytic therapy with alteplase can effectively improve the functional prognosis in acute ischemic stroke. Thus all guidelines recommended the intravenous thrombolytic therapy with alteplase for acute ischemic stroke within 4.5 hours from stroke onset.

Minor stroke is usually defined as NIHSS score ≤ 3 or 5，although it accounts for 1/2-2/3 of AIS, the evidence of thrombolysis is insufficient. A study from Canada shows that 28.5% of patients with minor stroke who have not receive rt-pa thrombolytic therapy are unable to walk independently when discharged. Based on such a consideration,the PRISMS study further compares the efficacy and safety of thrombolytic therapy with antithrombotic therapy in patients with minor stroke. Unfortunately, the study has been early terminated due to the sponsorship reason in 2018, with only 313 cases enrolled. The preliminary results shows that there is no significant difference of the 90-day neurological function between the two groups, while the safety of the treatment group with alteplase has a higher rate of symptomatic intracranial hemorrhage. The patient receiving thrombolysis can not be given antithrombolytic therapy within 24 hours even if the patient's condition has worsened, is clinically more puzzling.

The CHANCE study in 2013 shows that the efficacy of aspirin with clopidogrel is superior to aspirin alone with minor stroke (NIHSS \< 3) or TIA(ABCD2 \< 4). The POINT study in 2018 further confirmed the efficacy and safety of intensive antithrombotic therapy within 12 hours of onset with minor stroke.

Based on the above discussion, this study aims to explore the efficacy and safety of aspirin with clopidogrel vs alteplase in the treatment of acute minor stroke.


Eligibility criteria: Inclusion Criteria:

1. Patient age ≥18 years;
2. Study treatment can be started within 4.5h;
3. Ischemic stroke confirmed by head CT or MRI;
4. NIHSS score ≤ 5, and ≤ 1 NIHSS score in single item scores such as vision, language, neglect and single limb and no score in consciousness item;
5. Premorbid mRS ≤ 1;
6. Signed informed consent

Exclusion Criteria:

1. Serious neurological deficits before onset ( mRS ≥ 2)；
2. Obvious head injuries or strokes within 3 months；
3. Subarachnoid hemorrhage;
4. History of intracranial hemorrhage;
5. Intracranial tumor, arteriovenous malformation or aneurysm;
6. Intracranial or spinal cord surgery within 3 months;
7. Arterial puncture at a noncompressible site within the previous seven days;
8. Gastrointestinal or urinary tract hemorrhage within the previous 21 days;
9. Major surgery within 1 month;
10. Systolic pressure ≥180 mmHg or diastolic pressure ≥110 mmHg;
11. Blood glucose \< 50 mg/dl (2.7mmol/L);
12. Heparin therapy or oral anticoagulation therapy within 48 hours;
13. Platelet count of \<100,000/mm3 (This does not need to be verified prior to randomization if clinical abnormality is not suspected);
14. Oral warfarin is being taken and INR\>1.6;
15. Abnormal APTT;
16. Pregnancy;
17. Neurological deficit after epileptic seizures;
18. Myocardial infarction within 3 months;
19. Cerebral infarction with definite anticoagulation indications, such as cerebral infarction caused by cardiogenic embolism;
20. Oral administration is not allowed due to dysphagia;
21. allergy to study drugs;
22. Other serious illness that would confound the clinical outcome at 90 days;
23. Participating in other clinical trials within 3 months;
24. patients not suitable for this clinical studies considered by researcher;

Primary outcomes:
measure: Proportion of mRS (0-1）
timeFrame: 90±7 days
Secondary outcomes:
measure: Proportion of mRS (0-2）
timeFrame: 90±7 days
measure: change in NIH Stroke Scale score compared with baseline
timeFrame: 24 hours
measure: incidence of early neurological improvement
timeFrame: 24 hours
measure: Incidence of early neurological deterioration
timeFrame: 7 days
measure: occurrence of stroke or other vascular events
timeFrame: 90±7 days
measure: proportion of death of any cause
timeFrame: 90±7 days
measure: occurrence of symptomatic intracranial hemorrhage
timeFrame: 90±7 days
measure: proportion of any bleeding events
timeFrame: 90±7 days
Other outcomes:
Locations:
city: ShenYang
country: China
facility: Lin Tao
Study officials:
affiliation: Neurology Department
name: Huisheng Chen, Doctor
role: STUDY_CHAIR
References: