Minocycline for Acute Ischemic Stroke Undergoing Endovascular Treatment Due to Basilar Artery Occlusion (MIST-B)

NCT05512910 | Active Not Recruiting Phase 4 DMC

• 1 other identifier: XJLL-KY20222184
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multi-center, evaluator-blinded, randomized, open-label, proof of concept trial to explore possible beneficial effect of adjunctive oral minocycline on acute ischemic stroke (AIS) undergoing endovascular treatment due to basilar artery occlusion (BAO). Minocycline has excellent safety profiles, have been previously demonstrated individually to reduce infarction in animal models of stroke, and have potentially mechanisms of antioxidant, anti-inflammatory, anti-apoptotic and protection of blood-brain barrier. However, it is not known whether minocycline can reduce futile recanalization of endovascular treatment, and improve the outcome of patients with AIS due to BAO. Eligible and willing subjects will be randomly assigned to the treatment group or the control group. The treatment group will receive 200 mg oral minocycline, followed by 100 mg every 12 hours times for a total of 5 days. Both groups will receive endovascular thrombectomy and standard medical. The treatment with minocycline will start as soon as possible after randomization. Considering the risk of difficulty in feeding tube before EVT, minocycline administered within one hours after EVT is acceptable. Measures of stroke severity and disability will be recorded at baseline and through the follow-up periods (90 days). The evaluator will be blind to the allocation of patients further minimizing the bias.

Conditions

Ischemic Stroke, Acute; Minocycline; Endovascular Treatment; Basilar Artery Occlusion

Keywords

Ischemic Stroke; Basilar Artery Occlusion; Endovascular Treatment; Minocycline; Neuroprotection; Futile Recanalization

Outcome Measures

Primary Outcomes (2)

• The expanded NIH Stroke Scale (e-NIHSS) at 5-7 days or at discharge

  The primary effectiveness outcome was the e-NIHSS score at 5-7 days or at discharge. 11-item neurologic examination scale for severity of posterior circulation stroke, adding specific elements in existing items of NIHSS.

  5-7 days or discharge after onset

• Incidence of symptomatic intracranial hemorrhage at 24 hours from randomization

  The primary safety outcome was the incidence of symptomatic intracranial hemorrhage, defined as neurological deterioration (≥4-point increase on the NIHSS score) within 24 hours from randomization and evidence of intracranial hemorrhage on imaging studies.

  24 hours from randomization

Secondary Outcomes (20)

• mRS at 90 (±14) days

  90 (±14) days from randomization

• Good outcome at 90 (±14) days from randomization

  90 (±14) days from randomization

• Favorable outcome at 90 (±14) days from randomization

  90 (±14) days from randomization

• Excellent outcome at 90 (±14) days from randomization

  90 (±14) days from randomization

• NIH Stroke Scale (NIHSS) at 24 hours, 5-7 days or discharge, 30 (±7) days and 90 (±14) days from randomization

  90 (±14) days from randomization

Study Arms (2)

Treatment group

EXPERIMENTAL

Patients randomized to the treatment group will receive oral minocycline in addition to endovascular treatment and other standard medical. The first dose of minocycline will be administered 200 mg orally, followed by 100 mg every 12 hours times for a total of 5 days. After randomization, oral minocycline should be given as soon as possible before the EVT treatment. If vomiting occurs within half an hour of the first dose, the clinician should assess the necessary of re-administering 100mg based on the severity of vomiting. If the patient is considered to be at any risk for aspiration or is unable to swallow based on swallowing evaluation, study drug will be oral via feeding tube. Considering the risk of difficulty in feeding tube before EVT, minocycline administered within one hours after EVT is acceptable.

Drug: Minocycline

Control group

NO INTERVENTION

Patients randomized to the control group will receive endovascular treatment and other standard treatment, without minocycline treatment.

Interventions

Minocycline DRUG

200 mg minocycline orally or via feeding tube, followed by 100 mg every 12 hours times for a total of 5 days. If vomiting occurs within half an hour of the first dose, the clinician should assess the necessary of re-administering 100mg based on the severity of vomiting. Considering the risk of difficulty in feeding tube before EVT, minocycline administered within one hours after EVT is acceptable.

Also known as: Minocycline hydrochloride

Treatment group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years old.
• Patients had acute symptoms and signs compatible with ischemia due to basilar artery occlusion (BAO), treated with endovascular therapy. Patients with occlusion of intracranial segments of both vertebral arteries (VA) resulting in no flow to the basilar artery (eg, functional basilar artery occlusion) were also eligible for the study.
• Last known well to groin puncture between 0 to 24 hours, whether or not patients had thrombolysis with rt-PA.
• Pre-stroke mRS score of 0-1.
• Baseline expanded NIHSS (e-NIHSS) score ≥ 6.
• Signed Informed Consent obtained.

You may not qualify if:

• Age\<18 years old.
• Complete cerebellar infarct with significant mass effect or has the imaging features of acute hydrocephalus in NCCT.
• Intracranial hemorrhage.
• Previous stroke in the past 90 days;
• cardiopulmonary resuscitation was performed within 10 days prior to onset.
• Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency, INR \>3, or platelet\<40×109/L.
• Glucose \<2.2 or \>22 mmol/L.
• Systolic blood pressure persistently\>185mmHg post-MT despite antihypertensive intervention; Diastolic blood pressure persistently\>110mmHg post-MT despite antihypertensive intervention.
• Acute or chronic renal failure of CKD grade 3-4.
• Known allergy or hypersensitivity to contrast dye or tetracycline group of drugs.
• Epileptic seizure at symptom onset.
• Life expectancy (except for stroke) \< 3 months.
• Female who is pregnancy or breastfeeding, or whom do not use effective contraception at childbearing age.
• Pre-existing mental illness that interferes with neurological evaluation.
• Known current participation in another clinical investigation with experimental drug.

Sponsors & Collaborators

• Xijing Hospital: lead
• Xi'an No.3 Hospital: collaborator
• Xi'an Gaoxin Hospital: collaborator
• First People's Hospital of Xianyang: collaborator
• Xi'an XD Group Hospital: collaborator
• Central Hospital of Gansu Province: collaborator

Study Sites (1)

Department of Neurology, Xijing Hospital, Fourth Military Medical University

Xi'an, Shaanxi, 710032, China

Location

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MeSH Terms

Conditions

Ischemic Stroke; cyclopia sequence

Interventions

Minocycline

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: All study staff is not masked to randomization except the following: independent outcome assessor and statistician.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ph.D

Study Record Dates

• First Submitted: August 18, 2022
• First Posted: August 23, 2022
• Study Start: March 4, 2023
• Primary Completion: March 11, 2025
• Study Completion: June 4, 2025
• Last Updated: May 30, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)