Efficacy and Safety of Sarecycline in Patients With Acute Ischemic Stroke After Reperfusion Therapy

Study Overview
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Brief Summary
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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
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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.

Official Title
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Efficacy and Safety of Sarecycline in Patients With Acute Ischemic Stroke After Reperfusion Therapy: A Phase II, Randomized, Multicenter, Double-blind, Single Dose, Placebo-controlled Parallel Trial

Conditions
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Ischemic Stroke, Acute

Intervention / Treatment
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* Drug: Sarecycline Tablet
* Drug: Placebo tablets of Sarecycline tablets


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: 18≤Age≤80 years old; 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; ASPECTS≥6; 7≤NIHSS≤25,and Ia≤1; 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); First stroke or complete self-care before the onset of current stroke (mRS 0-1); Patients or his/her legal representatives are able to understand and sign the informed consent. Exclusion criteria: History of pseudomembranous colitis or antibiotic-related colitis. Allergic to tetracycline antibiotics or any component of the investigational drug. Known to be resistant to other tetracyclines. History of intracranial hemorrhagic diseases within the previous 3 months, including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/external hematoma, etc. Intracranial tumors, vascular malformations, and other intracranial space-occupying lesions. Bilateral or posterior circulation LVO. Rare or unknown etiology of LVO, such as dissection and vasculitis. 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). 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. Received any of the following treatments within the previous 3 months: systemic retinoic acid, androgen/antiandrogen therapy (e.g., anabolic steroids, andiolactone). Refractory hypertension that is difficult to control with medication (systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg). History of intracranial or spinal surgery within the previous 3 months; History of therapeutical surgery or major physical trauma within the previous 1 month. Have other investigator-evaluated contraindications of reperfusion therapy. Women of childbearing age who do not use effective contraception and have no negative pregnancy test records; Women during lactation and pregnancy. Life expectancy of fewer than 6 months due to advanced stage of any comorbidity. Participated in other interventional clinical trials within the previous 3 months. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sarecycline treatment group<br>The first dose should be given immediately after randomization (within 30 minutes); Take one tablet once a day for 7 days continuously (the patient with dysphagia will be administrated through a nasal feeding tube). | Drug: Sarecycline Tablet<br>* Each tablet contained 100 mg of Sarecycline.<br>|
| Placebo Comparator: Sarecycline placebo control group<br>The control group received Sarecycline placebo tablets (each containing Sarecycline 0 mg) in the same way as the experimental group. | Drug: Placebo tablets of Sarecycline tablets<br>* Each tablet contained 0 mg of Sarecycline.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of NIHSS score between baseline and at 7 days after randomization. | National Institute of Health stroke scale (NIHSS 0-42 scores; higher scores mean a worse outcome） | at 7 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of NIHSS score between baseline and 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） | within 2 hours after reperfusion | 
| Changes of NIHSS score between baseline and 72 hours after randomization. | National Institute of Health stroke scale (NIHSS 0-42 scores; higher scores mean a worse outcome） | at 72 hours after randomization | 
| Early neurological deterioration at 72 hours after randomization. | Early neurological deterioration | at 72 hours after randomization. | 
| Early neurological deterioration at 7 days after randomization. | Early neurological deterioration | at 7 days after randomization | 
| Changes of infarction volume between baseline and at 72 hours after randomization. | Infarction volume | at 72 hours after randomization | 
| Changes of cerebral blood perfusion between baseline and at 72 hours after randomization. | Cerebral blood perfusion evaluated by CTP | at 72 hours after randomization | 
| Changes of collateral circulation compensation between baseline and at 72 hours after randomization. | Collateral circulation compensation | at 72 hours after randomization | 
| Modified Rankin Scale (mRS) score at 90 days after randomization. | Modified Rankin Scale (mRS 0-5 scores; higher scores mean a worse outcome） | at 90 days after randomization | 
| Quality of life (EQ-5D) score at 90 days after randomization. | EuroQol Five Dimensions Questionnaire | at 90 days after randomization | 
| The proportion of combined vascular events (recurrent stroke, myocardial infarction, and vasogenic death) at 90 days after randomization. | Combined vascular events (recurrent stroke, myocardial infarction, and vasogenic death) | at 90 days after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ischemic Stroke, Sarecycline