Minocycline After Successful Endovascular Thrombectomy Recanalization in Acute Anterior Circulation Large Vessel Occlusion (ATTRACTION-MINOA)

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

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.

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.

Inclusion Criteria:

1. Age ≥18 years;
2. Pre-stroke mRS score of 0-1;
3. 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;
4. Baseline NIHSS score of 6-25;
5. ASPECTS ≥6 on non-contrast CT or DWI;
6. 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;
7. 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;
8. Ability of the patient or legally authorized representative to provide written informed consent.

Exclusion Criteria:

1. Acute intracranial hemorrhage on CT or MRI;
2. Bilateral acute stroke or multiple intracranial large vessel occlusions;
3. Isolated extracranial internal carotid artery occlusion;
4. History of pseudomembranous colitis or antibiotic-associated colitis;
5. Known allergy to tetracycline antibiotics, any component of the investigational drug, radiocontrast agents, or nitinol materials;
6. Known resistance to tetracycline antibiotics;
7. Use of tetracycline antibiotics within 7 days prior to randomization;
8. History of intracranial hemorrhage within the past 3 months, including intraparenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural hematoma, or epidural hematoma;
9. Intracranial tumors, vascular malformations, or other space-occupying intracranial lesions;
10. History of intracranial or spinal surgery within the past 3 months;
11. History of major surgery or significant trauma within the past 1 month;
12. Receipt of any of the following treatments within the past 3 months: systemic retinoic acid or androgen/antiandrogen therapy (e.g., anabolic steroids, spironolactone);
13. Platelet count <100 × 10⁹/L;
14. 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]);
15. Women who are pregnant or lactating, or who have a positive pregnancy test prior to randomization;
16. Life expectancy <6 months (e.g., due to malignancy or severe cardiopulmonary disease);
17. Participation in another interventional clinical trial that may affect outcome assessment;
18. 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).