Acute Ischemic Stroke Clinical Trial
— CRYSTALOfficial title:
Cilostazol Dexborneol Versus Placebo for Microcirculation Dysfunction After Reperfusion Therapy in Patients With Acute Ischemic Stroke With Large Vessel Occlusion: A Phase Ⅱa,Prospective,Multicenter,Randomized, Double-blind,Placebo-controlled Parallel Trial
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.
Status | Recruiting |
Enrollment | 120 |
Est. completion date | August 2024 |
Est. primary completion date | July 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 35 Years to 80 Years |
Eligibility | 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. |
Country | Name | City | State |
---|---|---|---|
China | Hunan Provincial People's Hospital | Changsha | Hunan |
China | Liuzhou Workers' Hospital | Liuzhou | Guangxi |
China | Pingxiang people's hospital | Pingxiang | Jiangxi |
Lead Sponsor | Collaborator |
---|---|
Beijing Tiantan Hospital | NeuroDawn Pharmaceutical Co., Ltd. |
China,
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* Note: There are 27 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Integrity evaluation of BBB by FEXI at 96 ± 7 hours after randomization | BBB permeability is assessed by FEXI | 96 ± 7 hours after randomization | |
Other | Integrity evaluation of BBB by FEXI at 28 ± 3 days after randomization | BBB permeability is assessed by FEXI | 28 ± 3 days after randomization | |
Other | Differences of indicators of venous thrombotic inflammation (plasma sGPVI, sADAMTS 13, sCD40L levels) and indirect indicators of BBB disruption (MMP-9, S100B) between baseline and 14±2 days of randomization | Collecting blood samples to evaluate venous thrombotic inflammation (plasma sGPVI, sADAMTS 13, sCD40L levels) and indirect indicators of blood-brain barrier disruption (MMP-9, S100B) | 14±2 days of randomization compared with baseline | |
Other | Differences of indicators of venous thrombotic inflammation (plasma sGPVI, sADAMTS 13, sCD40L levels) and indirect indicators of BBB disruption (MMP-9, S100B) between baseline and 24±2 hours of randomization | Collecting blood samples to evaluate venous thrombotic inflammation (plasma sGPVI, sADAMTS 13, sCD40L levels) and indirect indicators of blood-brain barrier disruption (MMP-9, S100B) | 24±2 hours of randomization compared with baseline | |
Primary | Proportion of mRS score recovered to 0~1 score | The modified Rankin Scale (mRS) decreasing to 0~1 score. mRS Mainly measures patients' independent living ability, including physical function, activity ability and participation in daily life. A score of 0 on the mRS Scale indicates no symptoms and a score of 5 indicates severe disability. | 90±7 days after randomization | |
Secondary | The mRS score at 90±7 days after randomization | The modified Rankin Scale (mRS) evaluated at 90±7 days after randomization. mRS Mainly measures patients' independent living ability, including physical function, activity ability and participation in daily life. A score of 0 on the mRS Scale indicates no symptoms and a score of 5 indicates severe disability. | 90±7 days after randomization | |
Secondary | Integrity of BBB evaluated by DCE | BBB permeability is assessed by DCE-MRI | 96±7 hours after randomization | |
Secondary | Changes of NIHSS score between baseline and immediately after reperfusion therapy | NIHSS score after reperfusion therapy within 2 hours changing compared with baseline NIHSS. The NIHSS score ranges from 0 to 42. The higher the score, the more severe the nerve damage. | immediately after reperfusion therapy (within 2 hours) | |
Secondary | Changes of NIHSS score between baseline and at 24 ± 2 hours, 96 ± 7 hours, 14 ± 2 days and 28 ± 3days after randomization | NIHSS score changing compared with baseline NIHSS. The NIHSS score ranges from 0 to 42. The higher the score, the more severe the nerve damage. | 24 ± 2 hours, 96 ± 7 hours, 14 ± 2 days and 28 ± 3 days after randomization and baseline NIHSS score | |
Secondary | Proportion of study patients with early progression of stroke at 24 ± 2 hours and 96 ± 7 hours after randomization | NIHSS score increasing by = 2 points, or the score of hemiplegia increasing by=1 point, or the score of conscious disturbance increasing by = 1 point compared with baseline within 7 days of onset, and intracranial hemorrhage is excepted by CT or MRI. Exacerbations not attributable to stroke are also excluded such as cardiac failure, liver and renal failure, etc. | 24 ± 2 hours and 96 ± 7 hours after randomization | |
Secondary | Proportion of study patients with combined vascular events at 90 ± 7 days after randomization | Symptomatic stroke, myocardial infarction and vascular death | 90 ± 7 days after randomization |
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