Cilostazol Dexborneol Versus Placebo for Microcirculation Dysfunction After Reperfusion Therapy in Patients With Acute Ischemic Stroke With Large Vessel Occlusion (CRYSTAL)

Capital Medical University

Status and phase: Enrolling; Phase 2

Conditions: Large Vessel Occlusion; Reperfusion; Acute Ischemic Stroke

Treatments: Drug: Y-6 sublingual tablets; Drug: Placebo tablets of Y-6 sublingual tablet

Study type: Interventional

Funder types: Other

Identifiers

NCT05836766

YW2022-046-03

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 120 estimated patients

Sex: All

Ages: 35 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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120 participants in 2 patient groups, including a placebo group

Y-6 sublingual tablets

Active Comparator group

Description:

Y-6 sublingual tablets (each tablet contains 25 mg cilostazol and 6 mg dexborneol) Manufacturer: Nanjing Neurodawn Pharmaceutical Co., Ltd.

Treatment:

Drug: Y-6 sublingual tablets

Placebo tablets of Y-6 sublingual tablet

Placebo Comparator group

Description:

Y-6 strength: Placebo tablets of Y-6 sublingual tablet (each tablet contains 0 mg cilostazol and 0.06 mg dexborneol) Manufacturer: Nanjing Neurodawn Pharmaceutical Co., Ltd.

Treatment:

Drug: Placebo tablets of Y-6 sublingual tablet