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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
90
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.
Department of Neurology, Xijing Hospital, Fourth Military Medical University
Xi'an, Shaanxi, China
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.
Time frame: 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.
Time frame: 24 hours from randomization
mRS at 90 (±14) days
Secondary outcome measure is the degree of disability or dependence at 90 (±14) days as assessed by the mRS scale. The scale runs from 0-6 with "0" being perfect health without symptoms to "6" being death.
Time frame: 90 (±14) days from randomization
Good outcome at 90 (±14) days from randomization
An mRS score of 0-3 indicated a good outcome, whereas a score of \>3 indicated a poor outcome.
Time frame: 90 (±14) days from randomization
Favorable outcome at 90 (±14) days from randomization
An mRS score of 0-2 indicated a favorable outcome, whereas a score of \>2 indicated a poor outcome.
Time frame: 90 (±14) days from randomization
Excellent outcome at 90 (±14) days from randomization
An mRS score of 0-1 indicated an excellent outcome, whereas a score of \>1 indicated a poor outcome
Time frame: 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
11-item neurologic examination scale for severity of stroke. Ratings for each item are scored with 3 to 5 grades. A total NIHSS of 0 is normal; 1-4 is considered a minor stroke; 5-15 moderate; 16-20 moderate to severe; and 21-42 severe.
Time frame: 90 (±14) days from randomization
Modified Barthel Index at 30 (±7) days and 90 (±14) days
The modified Barthel Index (mBI) is an ordinal scale used to measure performance in activities of daily living (ADL). The Barthel Index score are scored, a higher number being a reflection of greater ability to function independently following hospital discharge.
Time frame: 30 (±7) days and 90 (±14) days from randomization
Incidence of symptomatic intracranial hemorrhage at 3 days from randomization
The secondary safety outcome was the incidence of symptomatic intracranial hemorrhage, defined as neurological deterioration (≥4-point increase on the NIHSS score) within 3 days from randomization and evidence of intracranial hemorrhage on imaging studies.
Time frame: 3 days from randomization
Mortality at 90 (±14) days from randomization
All-cause mortality occurring within 90 (±14) days follow-up were recorded.
Time frame: 90 (±14) days from randomization
Change in infarct volume from baseline to day 5-7 or discharge
Changes of infarct volume from baseline (measured by DWI) to day 5-7 or discharge of stroke onset (measured by Flair). Images are processed by imSTROKE software.
Time frame: 5-7 days from randomization or discharge
Length of Intensive Care Unit (ICU) stay and hospital stay
Length of ICU or hospital stay
Time frame: From the date of admission until discharged from ICU or hospital, up to 4 weeks
Pneumonia at 5-7 days or discharge, 30 (±7) days and 90 (±14) days
Determine whether rates of pneumonia are different in the two arms. Rates will be measured as percentages of the entire population at risk.
Time frame: 90 (±14) days from randomization
Time of mechanical ventilation or non-invasive ventilation at 5-7 days or at discharge
Determine whether time of mechanical ventilation or non-invasive ventilation are different in the two arms. Rates will be measured as percentages of the entire population at risk.
Time frame: 5-7 days from randomization or discharge
Change in hematology assessments: percentage of the lymphocyte subpopulations (%) at 5-7 days or at discharge as compared to Baseline
The percentage of lymphocyte subpopulations in % will be assessed by flow cytometry.
Time frame: 5-7 days from randomization or discharge
Change in hematology assessments: matrix metalloproteinase-9 (ng/ml) at 5-7 days or at discharge as compared to Baseline
The level of matrix metalloproteinase-9 in ng/ml will be assessed by ELISA method.
Time frame: 5-7 days from randomization or discharge
Change in hematology assessments: IL-6 (pg/ml) at 5-7 days or at discharge as compared to Baseline
The level of IL-6 in pg/ml will be assessed by ELISA method.
Time frame: 5-7 days from randomization or discharge
Change in hematology assessments: IL-10 (pg/ml) at 5-7 days or at discharge as compared to Baseline
The level of IL-10 in pg/ml will be assessed by ELISA method.
Time frame: 5-7 days from randomization or discharge
Change in hematology assessments: TNF-α (nmol/L) at 5-7 days or at discharge as compared to Baseline
The level of TNF-α in nmol/L will be assessed by ELISA method.
Time frame: 5-7 days from randomization or discharge
Change in hematology assessments: leucocytes (x 10^9 /L) at 5-7 days or at discharge as compared to Baseline
Change in the level of leucocytes x 10\^9 /L.
Time frame: 5-7 days from randomization or discharge
Change in hematology assessments: neutrophilic granulocyte percentage (%) at 5-7 days or at discharge as compared to Baseline
Change in the neutrophilic granulocyte percentage in %.
Time frame: 5-7 days from randomization or discharge
Change in hematology assessments: absolute neutrophil value (x 10^9 /L) at 5-7 days or at discharge as compared to Baseline
Change in the level of absolute neutrophil value x 10\^9 /L.
Time frame: 5-7 days from randomization or discharge
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