Minocycline After Successful Endovascular Thrombectomy Recanalization in Posterior Circulation Arterial Occlusion (ATTRACTION-MINOP)

Safety and Efficacy of Adjunctive Minocycline After Successful Endovascular Thrombectomy Recanalization for Acute Posterior Circulation Arterial Occlusion - A Multicenter, Prospective, Double-blind, Randomized Trial

Acute ischemic stroke (AIS) is a leading cause of mortality and long-term disability worldwide. Among these, stroke caused by large vessel occlusion (LVO) are associated with particularly poor outcomes. Multiple randomized controlled trials have demonstrated that endovascular thrombectomy (EVT) significantly improves clinical outcomes in patients with acute LVO and is recommended as the standard of care by current guidelines. Posterior circulation strokes account for approximately 20% of all ischemic strokes and are generally associated with worse prognosis than anterior circulation strokes, especially in patients with basilar artery occlusion, who have a markedly increased risk of death or severe disability. Despite EVT treatment, more than three-quarters of these patients remain dead or functionally dependent at 90 days, indicating substantial room for improvement.

Successful recanalization and restoration of effective cerebral perfusion are critical for achieving favorable outcomes. However, although recanalization rates exceed 80% with current thrombectomy techniques, fewer than 40 of patients achieve good functional outcomes at 90 days, suggesting a high incidence of futile recanalization. The underlying mechanisms may include no-reflow, reperfusion injury, and microcirculatory dysfunction, all of which are closely associated with post-recanalization neuroinflammation.

Minocycline is a second-generation tetracycline with pleiotropic neuroprotective properties, including inhibition of microglial activation, reduction of inflammatory mediators, suppression of matrix metalloproteinases, attenuation of oxidative stress, and preservation of blood-brain barrier integrity. Preclinical and clinical studies suggest that minocycline may improve neurological outcomes in patients with AIS.

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 posterior circulation arterial occlusion who achieve successful recanalization after EVT. The trial will assess whether early administration of minocycline improves functional outcomes and reduces the incidence of 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 posterior circulation arterial occlusion 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 0-2 at 90 days. A total of 234 participants (117 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 ≥6;;
5. Posterior Circulation ASPECTS ≥6 on non-contrast CT or DWI;
6. Clinical symptoms attributable to acute occlusion of the intracranial vertebral artery or basilar artery, confirmed by CTA, MRA, or DSA;
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. Occlusion involving both anterior and posterior circulations on CTA, MRA, or DSA (except in patients with a prior history of anterior circulation occlusion);
3. Complete bilateral thalamic infarction or bilateral brainstem infarction on CT or MRI;
4. Cerebellar infarction with significant mass effect or compression of the fourth ventricle on CT or MRI;
5. Vascular anatomy on CTA, MRA, or DSA that is severely tortuous, demonstrates significant anatomical variation, or shows severe stenosis or dissection precluding navigation of thrombectomy devices to the target vessel;
6. History of pseudomembranous colitis or antibiotic-associated colitis;
7. Known allergy to tetracycline antibiotics, any component of the investigational drug, radiocontrast agents, or nitinol materials;
8. Known resistance to tetracycline antibiotics;
9. Use of tetracycline antibiotics within 7 days prior to randomization;
10. History of intracranial hemorrhage within the past 3 months, including intraparenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural hematoma, or epidural hematoma;
11. Intracranial tumors, vascular malformations, or other space-occupying intracranial lesions;
12. History of intracranial or spinal surgery within the past 3 months;
13. History of major surgery or significant trauma within the past 1 month;
14. Receipt of any of the following treatments within the past 3 months: systemic retinoic acid or androgen/antiandrogen therapy (e.g., anabolic steroids, spironolactone);
15. Platelet count <100 × 10⁹/L;
16. 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]);
17. Women who are pregnant or lactating, or who have a positive pregnancy test prior to randomization;
18. Life expectancy <6 months (e.g., due to malignancy or severe cardiopulmonary disease);
19. Participation in another interventional clinical trial that may affect outcome assessment;
20. 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).