Reperfusion Injury After Cerebral Ischemia: an "in Vivo" Study Using Neuro-imaging Markers
试验速览
- 阶段
- 不适用
- 入组人数
- 140
- 试验地点
- 1
- 主要终点
- Number of patients with hemorrhagic transformation (type 2 OR any type of parenchyma hemorrhage according to ECASS II criteria) OR cerebral edema (comprising at least 1/3 of the hemisphere OR causing midline shift) at 24h CT
研究概览
简要总结
Background: stroke is a major cause of death and disability. Intravenous thrombolysis and mechanical thrombectomy are able to re-open occluded vessels and save the ischemic tissue from death. However, recanalization of the occluded vessel may trigger activation of detrimental molecular pathways and exacerbate blood brain barrier (BBB) disruption, eventually determining hemorrhagic transformation (HT) or cerebral edema (CE), causing the so-called "reperfusion injury". There is increasing evidence that a number of factors measurable as circulating biomarkers, particularly metalloproteinases (MMP), contribute to reperfusion brain injury. Preliminary data show that BBB disruption can be traced in vivo by Computed Tomography Perfusion (CTP) imaging. The aim of this study is to evaluate the effects of circulating and imaging biomarkers in relation to reperfusion injury.
Methods: consecutive patients presenting with acute ischemic stroke in the anterior circulation territory, scoring≥7 on NIHSS, candidates to intravenous thrombolysis or to endovascular treatment, will be enrolled in one hospital centre. Circulating levels of pro-, anti-inflammatory, immunomodulatory factors, metalloproteinases and their inductors/inhibitors, factors of endothelial dysfunction and fibrin resistance to lysis will be measured in blood samples taken from each patients pre-thrombolysis and 24 hours after thrombolysis. Biomarker levels will be studied in relation to CTP measures of BBB permeability and in relation to imaging signs of reperfusion injury after acute interventions, such as hemorrhagic transformation and cerebral edema.
Results: enrollment started on October 2015. As of January 2017, 70 patients have been included. Results are expected by the end of 2018 with an estimated sample size of 140 patients. Using a definite protocol, a prospective collection of data, and an adequate number of patients assuring statistically powered data, this study will integrate clinical information with imaging and biological factors involved in reperfusion injury after cerebral ischemia.
详细描述
Study design:
This is an observational hospital-based study that will include 140 patients with ischemic stroke in the anterior circulation within 12 hours from last seen well, treated either with intravenous thrombolysis or endovascular thrombectomy. Included patients have National Institutes of Health Stroke Scale (NIHSS) ≥7. Both circulating biomarkers sampling and CT Perfusion will be performed before acute interventions. Clinical/functional and imaging assessments will be repeated 24 hours after interventions and at 3 months after stroke.
Work Methodology:
Stroke severity will be measured using the NIHSS, post-stroke disability by the modified Rankin Scale (mRS) administered at 3 months by visit or phone interview. Investigators will rate hemorrhagic transformation (HT) grade using the European Cooperative Acute Stroke Study (ECASS II) criteria and CE according to the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) protocol.
Cerebral imaging will include baseline plain CT, CT angiography and CT perfusion at baseline. CT will be repeated at 24 h, and at any time when clinical deterioration will be observed. Collection of imaging data will be blinded to both clinical and laboratory data. Baseline and follow up CT scans will be assessed by three stroke physicians (FA, BP, VP) for presence of early ischemic signs (Alberta Stroke Programme Early CT score, hyperdensity of middle cerebral artery), presence and severity of small vessel disease markers (white matter changes, preexisting lacunar infarcts, brain atrophy), presence and grading of HT, when present. Perfusion maps will be generated for each patient with a deconvolution-based delay-insensitive algorithm. For permeability calculation, an adiabatic approximation of distributed parameter analysis will be used. Permeability maps will be generated by a dedicated software. Recanalization rate will be assessed at 24 hours with either CT angiography, Magnetic Resonance angiography or transcranial doppler. In case of effective recanalization (Thrombolysis In Cerebral Infarction scale=2b/3) at the end of endovascular procedure and clinical improvement, recanalization will not be reassessed at 24 hours.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Ischemic stroke patients in the anterior circulation territory
- •within 12 hours from last seen well
排除标准
- •Controindications for iodine contrast medium
结局指标
主要结局
Number of patients with hemorrhagic transformation (type 2 OR any type of parenchyma hemorrhage according to ECASS II criteria) OR cerebral edema (comprising at least 1/3 of the hemisphere OR causing midline shift) at 24h CT
时间窗: 24 hours from symptom onset
Relevant Hemorrhagic Transformation OR Relevant Cerebral Edema
次要结局
- Categorical shift in mRS score at 3 months(3 months from symptom onset)
- Symptomatic hemorrhagic transformation(24 hours from symptom onset)
研究者
Domenico Inzitari
Professor
University of Florence