Clinical trial NCT05512910: Minocycline for Acute Ischemic Stroke Undergoing Endovascular Treatment Due to Basilar Artery Occlusion (MIST-B)
Official title: Minocycline for Acute Ischemic Stroke Undergoing Endovascular Treatment Due to Basilar Artery Occlusion: a Randomized, Open-label, Proof of Concept Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Ischemic Stroke, Acute
Minocycline
Endovascular Treatment
Basilar Artery Occlusion
Keywords: Ischemic Stroke
Basilar Artery Occlusion
Endovascular Treatment
Minocycline
Neuroprotection
Futile Recanalization
Lead sponsor: Xijing Hospital
Sponsor class: OTHER
Collaborators: name: Xi'an No.3 Hospital
name: Xi'an Gaoxin Hospital
name: First People's Hospital of Xianyang
name: Xi'an XD Group Hospital
name: Central Hospital of Gansu Province
First posted: 2022-08-23
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years old.
2. 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.
3. Last known well to groin puncture between 0 to 24 hours, whether or not patients had thrombolysis with rt-PA.
4. Pre-stroke mRS score of 0-1.
5. Baseline expanded NIHSS (e-NIHSS) score ≥ 6.
6. Signed Informed Consent obtained.
7. Neuroimaging Inclusion Criteria: (1) Proven large vessel occlusion in BAO or VA-V4 occlusion (mTICI score 0-1) determined by MRA or CTA; (2) pc-ASPECTS score ≥ 5 (Non-Contrast CT or DWI); Pons-midbrain-index of\<3.

Exclusion Criteria:

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

Primary outcomes:
measure: The expanded NIH Stroke Scale (e-NIHSS) at 5-7 days or at discharge
timeFrame: 5-7 days or discharge after onset
measure: Incidence of symptomatic intracranial hemorrhage at 24 hours from randomization
timeFrame: 24 hours from randomization
Secondary outcomes:
measure: mRS at 90 (±14) days
timeFrame: 90 (±14) days from randomization
measure: Good outcome at 90 (±14) days from randomization
timeFrame: 90 (±14) days from randomization
measure: Favorable outcome at 90 (±14) days from randomization
timeFrame: 90 (±14) days from randomization
measure: Excellent outcome at 90 (±14) days from randomization
timeFrame: 90 (±14) days from randomization
measure: NIH Stroke Scale (NIHSS) at 24 hours, 5-7 days or discharge, 30 (±7) days and 90 (±14) days from randomization
timeFrame: 90 (±14) days from randomization
measure: Modified Barthel Index at 30 (±7) days and 90 (±14) days
timeFrame: 30 (±7) days and 90 (±14) days from randomization
measure: Incidence of symptomatic intracranial hemorrhage at 3 days from randomization
timeFrame: 3 days from randomization
measure: Mortality at 90 (±14) days from randomization
timeFrame: 90 (±14) days from randomization
measure: Change in infarct volume from baseline to day 5-7 or discharge
timeFrame: 5-7 days from randomization or discharge
measure: Length of Intensive Care Unit (ICU) stay and hospital stay
timeFrame: From the date of admission until discharged from ICU or hospital, up to 4 weeks
measure: Pneumonia at 5-7 days or discharge, 30 (±7) days and 90 (±14) days
timeFrame: 90 (±14) days from randomization
measure: Time of mechanical ventilation or non-invasive ventilation at 5-7 days or at discharge
timeFrame: 5-7 days from randomization or discharge
measure: Change in hematology assessments: percentage of the lymphocyte subpopulations (%) at 5-7 days or at discharge as compared to Baseline
timeFrame: 5-7 days from randomization or discharge
measure: Change in hematology assessments: matrix metalloproteinase-9 (ng/ml) at 5-7 days or at discharge as compared to Baseline
timeFrame: 5-7 days from randomization or discharge
measure: Change in hematology assessments: IL-6 (pg/ml) at 5-7 days or at discharge as compared to Baseline
timeFrame: 5-7 days from randomization or discharge
measure: Change in hematology assessments: IL-10 (pg/ml) at 5-7 days or at discharge as compared to Baseline
timeFrame: 5-7 days from randomization or discharge
measure: Change in hematology assessments: TNF-α (nmol/L) at 5-7 days or at discharge as compared to Baseline
timeFrame: 5-7 days from randomization or discharge
measure: Change in hematology assessments: leucocytes (x 10^9 /L) at 5-7 days or at discharge as compared to Baseline
timeFrame: 5-7 days from randomization or discharge
measure: Change in hematology assessments: neutrophilic granulocyte percentage (%) at 5-7 days or at discharge as compared to Baseline
timeFrame: 5-7 days from randomization or discharge
measure: Change in hematology assessments: absolute neutrophil value (x 10^9 /L) at 5-7 days or at discharge as compared to Baseline
timeFrame: 5-7 days from randomization or discharge
Other outcomes:
Locations:
city: Xi'an
country: China
facility: Department of Neurology, Xijing Hospital, Fourth Military Medical University
state: Shaanxi
Study officials:
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