The primary objective of the study will be to determine whether remote limb ischemic conditioning (RLIC) compared with sham RLIC (placebo) treatment reduces the 12-month risk of recurrent IS in patients with a recent TIA or IS caused by stenosis of a major intracranial artery.

After screening period, eligible patients will be randomly allocated into 2 groups. In addition, all participants receive an usual clinical therapy.

In this study, Patients in the RLIC group will be treated with Renqiao Remote Ischemic Conditioning Device (Doctormate®) (200mmHg) once daily for 12 months; patients in the sham RLIC group will be treated with the Renqiao Remote Ischemic Conditioning Device (Doctormate®) (60mmHg) once daily for 12 months. In the study, the RLIC treatment will be comprised of 5 cycles of bilateral upper limb ischemia and reperfusion, which will be induced by 2 cuffs placed around the upper arms respectively and inflated to 200mmHg for 5 minutes followed by 5 minutes of reperfusion by cuff deflation. Sham RLIC treatment will be conducted using the same procedure but with a minimal inflation pressure of 60mmHg, which does not result in upper limb ischemia. In addition, all participants will have received their usual drug therapy according to local medical practice.

Inclusion Criteria:

1. Male or female with age from 40 to 80 years old.

2. Patients having an ischemic stroke or a TIA prior to randomization.

   • Patient having an ischemic stroke within 30 days with mRS score≤4 at baseline.
   • Patient having a TIA within 15 days with Oxfordshire Community Stroke Project on the basis of age, blood pressure (BP), clinical features, and duration of TIA symptoms (ABCD2) score≥4 at baseline.

3. The entry event is attributed to symptomatic atherosclerotic stenosis (50-99%) in an intracranial qualifying artery (carotid artery, middle cerebral artery (M1), vertebral artery, or basilar artery) that is documented by magnetic resonance angiography (MRA) or computed tomographic angiography (CTA).

4. Informed consent obtained.

Exclusion Criteria:

1. Thrombolytic therapy within 24 hours prior to enrollment.
2. Progressive neurological signs within 24 hours prior to enrollment.
3. Cerebral venous thrombosis/stenosis.
4. Intracranial arterial stenosis due to arterial dissection, Moya Moya disease; any known vasculitic disease; herpes zoster, varicella zoster or other viral vasculopathy; neurosyphilis; any other intracranial infection; any intracranial stenosis associated with cerebrospinal fluid (CSF) pleocytosis; radiation induced vasculopathy; fibromuscular dysplasia; sickle cell disease; neurofibromatosis; benign angiopathy of central nervous system; post-partum angiopathy; suspected vasospastic process, suspected recanalized embolus.
5. Any of the following unequivocal cardiac source of embolism: rheumatic mitral and or aortic stenosis, prosthetic heart valves, atrial fibrillation, atrial flutter, sick sinus syndrome, left atrial myxoma, patent foramen ovale, left ventricular mural thrombus or valvular vegetation, congestive heart failure, bacterial endocarditis, or any other cardiovascular condition interfering with the participation.
6. Uncontrolled severe hypertension [sitting systolic blood pressure (SBP) >180 mmHg and/or sitting diastolic blood pressure (DBP) >110 mmHg after medication].
7. Patients with abnormal laboratory parameters: aspartate transaminase (AST) and/or alanine transaminase (ALT) >3×upper limit of normal range; creatinine clearance <0.6 ml/s and/or serum creatinine >265 μmol/l (>3.0 mg/dl); platelets <100×109/L.
8. Any intracranial hemorrhage (parenchymal, subarachnoid, subdural, epidural) within 90 days prior to enrollment.
9. Intracranial neoplasm, cerebral aneurysm or arteriovenous malformation.
10. Known retinal hemorrhage or visceral bleeding within 30 days prior to enrollment.
11. Severe hemostatic disorder or severe coagulation dysfunction.
12. Subclavian arterial stenosis≥50% or subclavian steal syndrome.
13. Extracranial stenosis ≥50%.
14. Previous treatment of target lesion with a stent, angioplasty, or other mechanical device, or plan to perform one of these procedures within 12 months after enrollment.
15. Major surgery (including open femoral, aortic, or carotid surgery, cardiac) within previous 30 days or scheduled in the 12 months after enrollment.
16. Contraindication for remote ischemic conditioning: severe soft tissue injury, fracture, or peripheral vascular disease in the upper limbs.
17. Life expectancy<3 years.
18. Pregnant or breast-feeding women.
19. Unwilling to be followed up or poor compliance for treatment.
20. Patients being enrolled or having been enrolled in other clinical trial within 3 months prior to this clinical trial.
21. Patients unsuitable for enrollment in the clinical trial according to investigators decision making.