Safety and Efficacy of Adjunctive Minocycline After Successful Endovascular Thrombectomy Recanalization for Acute Anterior Circulation Large Vessel Occlusion - A Multicenter, Prospective, Double-blind, Randomized Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 860
- 试验地点
- 1
- 主要终点
- Excellent outcome
研究概览
简要总结
Endovascular thrombectomy (EVT) improves outcomes in patients with acute large vessel occlusion (LVO). However, despite successful recanalization rates exceeding 80%, fewer than 50% of patients achieve favorable functional outcomes at 90 days, indicating a high rate of futile recanalization. Potential mechanisms include no-reflow, reperfusion injury, and microcirculatory dysfunction, which are closely associated with post-recanalization neuroinflammation.
Minocycline is a second-generation tetracycline with pleiotropic neuroprotective effects, including inhibition of microglial activation, reduction of inflammatory mediators, suppression of matrix metalloproteinases, attenuation of oxidative stress, and preservation of blood-brain barrier integrity. Prior preclinical and clinical studies suggest that minocycline may improve neurological outcomes in acute ischemic stroke.
This study is a multicenter, prospective, double-blind, randomized controlled trial designed to evaluate the safety and efficacy of adjunctive minocycline in patients with acute anterior circulation LVO who achieve successful recanalization after EVT. The trial will assess whether early administration of minocycline improves functional outcomes and reduces futile recanalization.
详细描述
This study is a multicenter, prospective, double-blind, randomized controlled trial designed to evaluate the safety and efficacy of adjunctive minocycline in patients with acute anterior circulation LVO who achieve successful recanalization after EVT. Eligible patients will be randomized in a 1:1 ratio to receive minocycline or placebo as soon as possible after randomization. Participants assigned to the intervention group will receive a loading dose of 200 mg of minocycline administered orally, followed by a maintenance dose of 100 mg every 12 hours for 4 days (total of 9 doses). Patients in the control group will receive a matching placebo according to the same schedule. For patients with swallowing dysfunction, administration via a feeding tube will be permitted. The primary outcome is the proportion of patients achieving a modified Rankin Scale (mRS) score of 0-1 at 90 days. A total of 860 participants (430 per group) will be enrolled.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The Minocycline drug used in the study is indistinguishable from the Minocycline 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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years;
- •Pre-stroke mRS score of 0-1;
- •Time from symptom onset to randomization ≤24 hours, including wake-up stroke or unwitnessed stroke. Symptom onset is defined as the last known well time;
- •Baseline NIHSS score of 6-25;
- •ASPECTS ≥6 on non-contrast CT or DWI;
- •Clinical symptoms attributable to acute occlusion at one of the following sites, confirmed by CTA, MRA, or DSA: intracranial internal carotid artery, M1 segment of the middle cerebral artery, or M2 trunk of the MCA;
- •Successful recanalization defined as mTICI 2b-3 after mechanical thrombectomy, with no evidence of secondary embolization in non-target vessels; or spontaneous improvement to mTICI 2b-3 on diagnostic angiography prior to thrombectomy with no planned intervention;
- •Ability of the patient or legally authorized representative to provide written informed consent.
排除标准
- •Acute intracranial hemorrhage on CT or MRI;
- •Bilateral acute stroke or multiple intracranial large vessel occlusions;
- •Isolated extracranial internal carotid artery occlusion;
- •History of pseudomembranous colitis or antibiotic-associated colitis;
- •Known allergy to tetracycline antibiotics, any component of the investigational drug, radiocontrast agents, or nitinol materials;
- •Known resistance to tetracycline antibiotics;
- •Use of tetracycline antibiotics within 7 days prior to randomization;
- •History of intracranial hemorrhage within the past 3 months, including intraparenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural hematoma, or epidural hematoma;
- •Intracranial tumors, vascular malformations, or other space-occupying intracranial lesions;
- •History of intracranial or spinal surgery within the past 3 months;
- •History of major surgery or significant trauma within the past 1 month;
- •Receipt of any of the following treatments within the past 3 months: systemic retinoic acid or androgen/antiandrogen therapy (e.g., anabolic steroids, spironolactone);
- •Platelet count <100 × 10⁹/L;
- •Severe hepatic insufficiency, chronic hemodialysis, or severe renal insufficiency (defined as estimated glomerular filtration rate <30 mL/min or serum creatinine >265.2 μmol/L [3.0 mg/dL]);
- •Women who are pregnant or lactating, or who have a positive pregnancy test prior to randomization;
- •Life expectancy <6 months (e.g., due to malignancy or severe cardiopulmonary disease);
- •Participation in another interventional clinical trial that may affect outcome assessment;
- •Any other condition that, in the investigator's judgment, makes the patient unsuitable for participation or poses significant risk (e.g., inability to understand or comply with study procedures or follow-up due to psychiatric, cognitive, or emotional disorders).
研究组 & 干预措施
placebo group
Participants with successful recanalization (mTICI 2b/3) after endovascular thrombectomy will receive placebo as soon as possible after randomization. Placebo was administered in the same manner as minocycline group.
干预措施: Placebo capsules of Minocycline hydrochloride capsules (Drug)
Minocycline group
Participants with successful recanalization (mTICI 2b/3) after endovascular thrombectomy will receive minocycline as soon as possible after randomization. A loading dose of 200 mg of minocycline administered orally, followed by a maintenance dose of 100 mg every 12 hours for 4 days (total of 9 doses). For patients with swallowing dysfunction, administration via a feeding tube will be permitted.
干预措施: Minocycline hydrochloride capsule (Drug)
结局指标
主要结局
Excellent outcome
时间窗: 90±7 days
Rate of modified Rankin scale (mRS) 0-1 at 90±7 days Defined as an modified Rankin Scale (mRS) score of 0 or 1. The mRS scores range from 0 (no symptoms) to 5 (severe disability) and 6 (death).
次要结局
- Ordinal distribution of mRS(90±7 days)
- Functional independence(90±7 days)
- Ambulatory or bodily needs-capable or better(90±7 days)
- Quality of life (EQ-5D-5L)(90±7 days)
- Neurologic deficit (NIHSS score) changes(24±12 hours and 6±1 days)
研究者
Xiang Luo
Principal Investigator
Tongji Hospital