Ischemic Stroke, Acute
Conditions
Keywords
Ischemic Stroke, Sarecycline
Brief summary
The aim of this study was to evaluate the efficacy and safety of Sarecycline versus placebo in the treatment of microcirculation dysfunction after reperfusion therapy in patients with large vessel occlusion stroke.
Detailed description
This study evaluated the efficacy and safety of 7-day Sarecycline versus placebo in patients with large vessel occlusion stroke who received reperfusion therapy within 24 hours of onset. In addition, we will explore the effect of Sarecycline versus placebo on indicators of venous thrombotic inflammation at different time points in patients with acute ischemic stroke with large vessel occlusion. This trial was a prospective, randomized, multicenter, double-blind, placebo-controlled parallel trial. Patients with acute large vessel occlusion stroke who received reperfusion therapy within 24 hours of onset were randomly assigned according to the ratio of the experimental group: control group =2:1. The trial was divided into three phases: screening/baseline period, treatment period, and follow-up period. The primary research objective is to evaluate the effect of Sarecycline in improving neurological deficits at 7 days in patients with acute large vessel occlusion stroke who received reperfusion therapy within 24 hours of onset.
Interventions
DRUGSarecycline Tablet
Each tablet contained 100 mg of Sarecycline.
DRUGPlacebo tablets of Sarecycline tablets
Each tablet contained 0 mg of Sarecycline.
Sponsors
Neurodawn Pharmaceutical Co., Ltd.
Beijing Tiantan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The Sarecycline drug used in the study is indistinguishable from the Sarecycline placebo (the shape, color, and appearance are identical). In addition, to ensure the blind method, the drug packaging and batch numbers of the two groups are identical, and the packaging batch numbers are uniformly marked. During the implementation of the study, except for the authorized personnel of the company's supply chain, research management department, and subject security department, members of each research execution group, research center personnel, and CRO data processing personnel cannot view the randomization scheme. The blind method was also used to evaluate the outcome. The subjects were randomly divided into groups and blinded to the members of the adjudication committee.
Intervention model description
This trial was a prospective, randomized, multicenter, double-blind, placebo-controlled parallel trial. Subjects were randomly assigned according to the ratio of the experimental group: control group =2:1.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. 18≤Age≤80 years old; 2. Acute large vessel occlusion (LVO) confirmed by imaging (CT+CTA+CTP/MRI+MRA), 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; 3. ASPECTS≥6; 4. 7≤NIHSS≤25,and Ia≤1; 5. Scheduled for reperfusion therapy within 24 hours of onset (including intravenous rt-PA or TNK-tPA thrombolysis (within 4.5 hours), mechanical thrombectomy, and bridging therapy); 6. First stroke or complete self-care before the onset of current stroke (mRS 0-1); 7. Patients or his/her legal representatives are able to understand and sign the informed consent.
Exclusion criteria
1. History of pseudomembranous colitis or antibiotic-related colitis. 2. Allergic to tetracycline antibiotics or any component of the investigational drug. 3. Known to be resistant to other tetracyclines. 4. History of intracranial hemorrhagic diseases within the previous 3 months, including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/external hematoma, etc. 5. Intracranial tumors, vascular malformations, and other intracranial space-occupying lesions. 6. Bilateral or posterior circulation LVO. 7. Rare or unknown etiology of LVO, such as dissection and vasculitis. 8. Severe hepatic or renal insufficiency and various reasons for receiving dialysis before randomization (Severe hepatic insufficiency was defined as ALT \>3 times the upper limit of normal value or AST \>3 times the upper limit of normal value; Severe renal insufficiency refers to serum creatinine \>3.0 mg/dl (265.2 μmol/L) or glomerular filtration rate\<30 ml/min). 9. Bleeding tendency (including but not limited to): platelet count \<100×109/L; Oral warfarin, INR \> 2; Received heparin within previous 48 hours, APTT≥35s; Hereditary hemorrhagic diseases, such as hemophilia. 10. Received any of the following treatments within the previous 3 months: systemic retinoic acid, androgen/antiandrogen therapy (e.g., anabolic steroids, andiolactone). 11. Refractory hypertension that is difficult to control with medication (systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg). 12. History of intracranial or spinal surgery within the previous 3 months; History of therapeutical surgery or major physical trauma within the previous 1 month. 13. Have other investigator-evaluated contraindications of reperfusion therapy. 14. Women of childbearing age who do not use effective contraception and have no negative pregnancy test records; Women during lactation and pregnancy. 15. Life expectancy of fewer than 6 months due to advanced stage of any comorbidity. 16. Participated in other interventional clinical trials within the previous 3 months. 17. Other conditions that are not suitable for participating in this clinical trial, such as inability to understand and/or follow the research procedures due to mental, cognitive, emotional, or physical disorders, etc.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes of NIHSS score between baseline and at 7 days after randomization. | at 7 days after randomization | National Institute of Health stroke scale (NIHSS 0-42 scores; higher scores mean a worse outcome） |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Early neurological deterioration at 72 hours after randomization. | at 72 hours after randomization. | Early neurological deterioration |
| Changes of infarction volume between baseline and at 72 hours after randomization. | at 72 hours after randomization | Infarction volume |
| Changes of cerebral blood perfusion between baseline and at 72 hours after randomization. | at 72 hours after randomization | Cerebral blood perfusion evaluated by CTP |
| Changes of collateral circulation compensation between baseline and at 72 hours after randomization. | at 72 hours after randomization | Collateral circulation compensation |
| Modified Rankin Scale (mRS) score at 90 days after randomization. | at 90 days after randomization | Modified Rankin Scale (mRS 0-5 scores; higher scores mean a worse outcome） |
| Quality of life (EQ-5D) score at 90 days after randomization. | at 90 days after randomization | EuroQol Five Dimensions Questionnaire |
| The proportion of combined vascular events (recurrent stroke, myocardial infarction, and vasogenic death) at 90 days after randomization. | at 90 days after randomization | Combined vascular events (recurrent stroke, myocardial infarction, and vasogenic death) |
| Changes of NIHSS score between baseline and within 2 hours after reperfusion. | within 2 hours after reperfusion | National Institute of Health stroke scale (NIHSS 0-42 scores; higher scores mean a worse outcome）al Institute of Health stroke scale (NIHSS 0-42 scores; higher scores mean a worse outcome） National Institute of Health stroke scale (NIHSS 0-42 scores; higher scores mean a worse outcome） |
| Changes of NIHSS score between baseline and 72 hours after randomization. | at 72 hours after randomization | National Institute of Health stroke scale (NIHSS 0-42 scores; higher scores mean a worse outcome） |
| Early neurological deterioration at 7 days after randomization. | at 7 days after randomization | Early neurological deterioration |
Other
| Measure | Time frame | Description |
|---|---|---|
| Any bleeding event. | at 90±7 days after randomization. | Any bleeding event was defined as any hemorrhagic event that occurred in the opinion of the investigator, including subcutaneous bleeding, gingival bleeding, gastrointestinal bleeding, intracranial bleeding, and other hemorrhagic events. |
| Vascular death. | At 90±7 days after randomization. | Vascular origin including death due to stroke death, sudden cardiac death, death due to acute myocardial infarction and death due to heart failure, pulmonary embolism, heart/cerebrovascular intervention operation (has nothing to do with acute MI) or surgery death and death from cardiovascular causes other(such as: sudden cardiac death had nothing to do with arrhythmia, aneurysm rupture, or peripheral artery disease). |
| Overall mortality. | At 90±7 days after randomization. | Death caused by any circumstances. |
| Investigator-reported adverse events/serious adverse events. | At 90±7 days of randomization. | Absolute platelet value ≤100×10\^9/L, high sensitivity reaction and kidney failure. |
| Venous thrombotic inflammation indicators compare with baseline. | within 2 hours after reperfusion therapy. | plasma sGPVI, sADAMTS 13, sCD40L levels. |
| Symptomatic intracranial hemorrhage. | at 24±2 hours after randomization | Heidelberg hemorrhage classification. |
Countries
China
Contacts
Primary ContactYilong Wang, PhD，MD
Outcome results
None listed