Acute Ischemic Stroke, Vessel Occlusion, Endovascular Thrombectomy, Anterior Circulation Brain Infarction, Minocycline
Conditions
Keywords
Acute Ischemic Stroke, Endovascular Thrombectomy, Minocycline, Anterior Circulation Large Vessel Occlusion
Brief summary
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.
Detailed description
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.
Interventions
50 mg per capsule, containing 50mg of Minocycline Hydrochloride.
50 mg per capsule, containing 0mg of Minocycline Hydrochloride.
Sponsors
Xiang Luo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Excellent outcome | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ordinal distribution of mRS | 90±7 days | The shift analysis of mRS at 90±7 days |
| Functional independence | 90±7 days | Rate of mRS 0-2 at 90±7 days |
| Ambulatory or bodily needs-capable or better | 90±7 days | Rate of mRS 0-3 at 90±7 days |
| Quality of life (EQ-5D-5L) | 90±7 days | The EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) index score at 90±7 days The EQ-5D-5L is a standardized, preference-based measure of health-related quality of life covering five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with five severity levels. The EQ-5D-5L index score typically ranges from less than 0 (health states worse than death) to 1.0 (full health), with higher scores indicating better quality of life. |
| Neurologic deficit (NIHSS score) changes | 24±12 hours and 6±1 days | The change of NIHSS score from baseline The NIHSS is a standardized clinical scale used to quantify neurologic impairment in stroke patients. The total score ranges from 0 to 42, with higher scores indicating more severe neurologic deficit. The outcome is defined as the change in NIHSS score from baseline, where a greater negative change reflects greater neurologic improvement. |
Countries
China
Contacts
CONTACTXiang Luo
PRINCIPAL_INVESTIGATORXiang Luo
Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 450001
Outcome results
None listed