cilostazol dexborneol versus placebo for microcirculation dysfunction after reperfusion therapy in patients with acute ischemic stroke with large vessel occlusion

Conditions: Acute Ischemic Stroke; Reperfusion; Large Vessel Occlusion

Summary: this study aims to evaluate the efficacy of y-6 sublingual tablets in improving microcirculation dysfunction and reducing thrombo-inflammation in patients who had ais caused by lvo and received reperfusion therapy. moreover, we expect to evaluate the safety of using y-6 sublingual tablet in such study population.

this study rationale is based on the following scheme: in patients with acute ischemic stroke caused by lvo, receiving reperfusion therapy may cause futile recanalization and thus lead to microcirculation dysfunction and thrombo-inflammation as consequences. cilostazol has antiplatelet effects and bbb protection and dexborneol has anti-inflammatory effects; therefore, the multi-component tablet may exert neuroprotective effects in terms of improving microcirculation dysfunction and reducing thrombo-inflammation in patients with ais after reperfusion therapy. the primary purpose of this study is to investigate the proportion of modified-rankin scale (mrs) score recovered to 0\~1 score at 90±7 days after randomization. the follow-up duration is 3 months, and the visit schedule is as follows: subjects enrolled based on randomization procedures will receive visits at screening/baseline period, first drug administration, immediately after reperfusion therapy(within 2 hours), 24 ± 2 hours, 96 ± 7 hours, 14 ± 2 days, 28 ± 2 days and 90 ± 7 days after randomization, and in case of any events.

Eligibility criteria:
inclusion criteria: * 35 years old ≤ age ≤ 80 years old * patients with acute ischemic stroke was diagnosed within 24 hours of onset (time from onset to completion of reperfusion therapy) * patients with first stroke or prior to stroke onset (mrs score 0-1) * patients with acute large vessel occlusion (lvo) confirmed by imaging, including the responsible vessel was located in the intracranial internal carotid artery, the t-shaped branch, the m1/m2 segment of the middle cerebral artery, or the a1/a2 segment of the anterior cerebral artery * aspects score ≥ 6 * 6\<nihss score ≤ 25 after the onset of this disease * patients who meet the indications for reperfusion therapy, including mechanical thrombectomy, bridging therapy (intravenous r-tpa thrombolytic therapy), and plan to undergo mechanical thrombectomy * patients or his/her legal representatives are able to understand and sign the informed consent exclusion criteria: * severe consciousness disturbance: nihss 1a consciousness level ≥2 points * patients with definite history of intracranial hemorrhage (such as subarachnoid hemorrhage, cerebral hemorrhage, etc.) * patients with intracranial tumor, arteriovenous malformation, or aneurysm * patients with bilateral anterior or posterior circulation ischemic stroke * patients with large vascular occlusion of rare or unknown etiology, such as dissection, vasculitis, etc. * patients who have received treatment with dual antiplatelet drugs, tirofiban, warfarin, novel oral anticoagulant, argatroban, snake venom, defibrase, lumbrokinase and other defibrase therapy after the onset of disease * patients with severe hepatic insufficiency or renal insufficiency and received dialysis for various reasons before randomization (severe hepatic insufficiency is defined as alt \> 3 × uln or ast \>3 × uln; severe renal insufficiency is defined as serum creatinine \>3.0 mg/dl (265.2 μmol/l) or creatinine clearance \< 30 ml/min) * patients with haemorrhagic diathesis (including but not limited to): platelet count \< 100 × 109/l; heparin treatment within the last 48 hours; taking oral warfarin; taking novel oral anticoagulant; administration with direct thrombin or xa factor inhibitors; with hereditary hemorrhagic disorders, such as hemophilia * patients with refractory hypertension that is difficult to be controlled by medication (systolic blood pressure \> 180 mmhg or diastolic blood pressure \> 110 mmhg) * patients with significant head trauma or stroke within 3 months prior to randomization * patients who have received intracranial or spinal surgery within 3 months prior to randomization * patients with history of major surgery or serious physical trauma within 1 month prior to randomization * patients with hemorrhagic retinopathy * male subjects (or their partners) or female subjects who had planned to have a child during the whole study period and within 3 months after the end of the study period or were unwilling to use one or more non-drug contraceptive methods (e.g., complete abstinence, condoms, ligation, etc.) during the study period * patients with contraindications to known contrast agent or other contrast agents; subjects who are allergic to cilostazol or dexborneol * patients who plan to receive other surgical or intervention therapy within 3 months, which might require discontinuation of the study drugs * patients with advanced disease, leading to life expectancy of \< 6 months * patients who have received treatment of investigational drug or device within 3 months * other conditions where it is not suitable for patients to participate in the clinical trial, such as inability to understand and/or follow the study procedures and/or follow-up schedule due to psychiatric disorders or cognitive/emotional disorders, or contraindications to thrombectomy or mri, etc.

Keywords: microcirculation dysfunction y-6 cilostazol dexborneol thrombo-inflammation acute ischemic stroke large vessel occlusion reperfusion therapy crystal