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.

Study Overview

• Status: Recruiting
• Conditions: Acute Ischemic Stroke; Arterial Occlusion; Minocycline; Endovascular Thrombectomy; Posterior Circulation
• Intervention / Treatment: Drug: Minocycline hydrochloride capsule; Drug: Placebo capsules of Minocycline hydrochloride capsules

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 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.

• Study Type: Interventional
• Enrollment (Estimated): 234
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Xiang Luo; Phone Number: +86-13349893413; Email: flydottjh@163.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Recruiting
      • Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Xiang Luo; Phone Number: +86-13349893413; Email: flydottjh@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Minocycline hydrochloride capsule; 50 mg per capsule, containing 50mg of Minocycline Hydrochloride.
Placebo Comparator: 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.	Drug: Placebo capsules of Minocycline hydrochloride capsules; 50 mg per capsule, containing 0mg of Minocycline Hydrochloride.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional independence	Rate of mRS 0-2 at 90±7 days Defined as an modified Rankin Scale (mRS) score of 0 to 2. The mRS scores range from 0 (no symptoms) to 5 (severe disability) and 6 (death).	90±7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ordinal distribution of mRS	The shift analysis of mRS at 90±7 days	90±7 days
Ambulatory or bodily needs-capable or better	Rate of mRS 0-3 at 90±7 days	90±7 days
Quality of life (EQ-5D-5L)	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.	90±7 days
Neurologic deficit (NIHSS score) changes	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.	24±12 hours and 6±1 days
Excellent outcome	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).	90±7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-caused mortality	All cause mortality at 90±7 days	90±7 days
Symptomatic intracranial hemorrhage (sICH)	Rate of sICH after randomization (Heidelberg Bleeding Classification)	24±12 hours and 6±1 days
Any intracranial hemorrhage	Rate of any intracranial hemorrhage after randomization (Heidelberg Bleeding Classification)	24±12 hours and 6±1 days
Adverse events and serious adverse events	Incidences of adverse events and serious adverse events	90±7 days

Collaborators and Investigators

• Sponsor: Xiang Luo
• Investigators: Principal Investigator: Xiang Luo, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 450001

Publications and helpful links

General Publications

• Lu Y, Guan L, Wu J, Yang Q, Zhang M, Zhou D, Yang H, Pan Y, Wang L, Qiu B, Liu C, Wang Y, Yang Y, Zhou X, Qu H, Liao X, Liu L, Zhao X, Bath PM, Johnston SC, Amarenco P, Turc G, Shi FD, Wang Y, Wang Y; EMPHASIS Investigators. Efficacy and safety of minocycline in patients with acute ischaemic stroke (EMPHASIS): a multicentre, double-blind, randomised controlled trial. Lancet. 2026 Feb 14;407(10529):679-688. doi: 10.1016/S0140-6736(25)01862-8. Epub 2026 Jan 30.

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: May 12, 2026
• First Submitted That Met QC Criteria: May 12, 2026
• First Posted (Actual): May 18, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Minocycline; Acute Ischemic Stroke; Endovascular Thrombectomy; Posterior Circulation Arterial Occlusion
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke; Arterial Occlusive Diseases; cyclopia sequence; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Naphthacenes; Tetracyclines; Minocycline
• Other Study ID Numbers: TJ-IRB202605010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No