Minocycline for Acute Ischemic Stroke Undergoing Endovascular Treatment Due to Basilar Artery Occlusion: a Randomized, Open-label, Proof of Concept Study
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- The expanded NIH Stroke Scale (e-NIHSS) at 5-7 days or at discharge
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
All study staff is not masked to randomization except the following: independent outcome assessor and statistician.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-
- •Baseline expanded NIHSS (e-NIHSS) score ≥
- •Signed Informed Consent obtained.
- •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.
排除标准
- •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-
- •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.
- •Unlikely to be available for 90 days follow-up.
研究组 & 干预措施
Treatment group
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.
干预措施: Minocycline (Drug)
结局指标
主要结局
The expanded NIH Stroke Scale (e-NIHSS) at 5-7 days or at discharge
时间窗: 5-7 days or discharge after onset
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.
Incidence of symptomatic intracranial hemorrhage at 24 hours from randomization
时间窗: 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.
次要结局
- Length of Intensive Care Unit (ICU) stay and hospital stay(From the date of admission until discharged from ICU or hospital, up to 4 weeks)
- 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)
- Modified Barthel Index at 30 (±7) days and 90 (±14) days(30 (±7) days and 90 (±14) days from randomization)
- Incidence of symptomatic intracranial hemorrhage at 3 days from randomization(3 days from randomization)
- Mortality at 90 (±14) days from randomization(90 (±14) days from randomization)
- Change in infarct volume from baseline to day 5-7 or discharge(5-7 days from randomization or discharge)
- Pneumonia at 5-7 days or discharge, 30 (±7) days and 90 (±14) days(90 (±14) days from randomization)
- Time of mechanical ventilation or non-invasive ventilation at 5-7 days or at discharge(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(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(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(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(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(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(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(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(5-7 days from randomization or discharge)
研究者
Wen Jiang-3
Ph.D
Xijing Hospital