New Predictive Biomarkers of Functional Recovery Prior the Endovascular Treatment of Acute Ischemic Stroke. PROMISE (Somatosensory Evoked POtEntials MonItoring During Acute Ischemic StrokE) Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 228
- 试验地点
- 1
- 主要终点
- Functional independence at 7 days or discharge
研究概览
简要总结
Endovascular treatment in patients with acute ischemic stroke due to large vessel occlusion does not always lead to good clinical and functional outcome, despite achieving complete arterial recanalization. The rate of significant functional disability or death after three months of an acute ischemic stroke still ranges from 40% to 67%. There is experimental and clinical evidence that somatosensory evoked potentials (SEPs) are good indicators of cerebral blood flow.
The primary objective of this study is to determine the sensitivity and specificity of N20 response of SEPs prior to mechanical thrombectomy (MT) as a predictor of functional independence at 90 days after endovascular treatment. Secondly, the investigators will study whether SEPs may be neurophysiological markers of brain tissue in ischemic penumbra and optimal collateral circulation.
Bilateral median nerve SEPs will be recorded before and continuously during MT in patients with acute ischemic stroke and anterior large vessel occlusion. N20 response ipsilateral to the cerebral hemisphere affected will be measured (qualitatively and quantitatively). The adjusted predictive value of the N20 biomarker on functional independence after MT will be analyzed by binary logistic regression and its predictive value on the full range of disability by ordinal logistic regression. The investigators will construct different regression models with other clinical predictors available at the prehospital setting and with those determined after hospital admission to determine the independent predictive power of the N20 response for a potential treatment decision-making. Finally, the investigators will study whether SEP can be neurophysiological markers ischemic penumbra tissue and optimal collateral circulation through its correlation with multimodal neuroimaging techniques.
SEPs recording is non-invasive technique that can be performed at the bedside of the patient. The development of a portable device which could allow SEPs recording by sanitary staff (pre- and intrahospitally) would provide early data about N20 value, speeding up streamline decision making.
详细描述
PROMISE (somatosensory evoked PotEntials MonItoring during the acute ischemic StrokE) is a prospective, observational, single center study of somatosensory evoked potentials (SEPs) monitoring with blinded clinical and neuroimaging evaluation of a cohort of patients with acute ischemic stroke undergoing endovascular mechanical thrombectomy (MT). The study is conducted under clinical routine protocols following the ESO and ASA guidelines (29). All patients, or their surrogates, provide written informed consent for using their clinical data for the research purposes.
The study has been designed to confirm in a large cohort a diagnostic hypothesis previously tested in a pilot academic study. The invention, as a solution to a specific technological problem, novelty, usefulness, and non-obviousness, has been protected by an European patent. The pilot study was founded by our academic Institution. This confirmatory study aims to validate the presence of the N20 response on SEPs monitoring prior to- and during the mechanical thrombectomy (MT) as a non-invasive and useful biomarker of functional recovery after MT.
Patients Recruitment period has started in February 2018 and will be open until June 2020 since the project end is expected for December 2020. Eligible patients are older than 18 years with an score equal or less of 2 in the modified Rankin Scale, and an occlusion in the anterior circulation (M1 or M2 segment of middle cerebral artery with or without ipsilateral internal carotid artery (ICA) significant stenosis or occlusion diagnosed by CT angiography (CTA) or angio-MRI) The study site is a certified comprehensive stroke center (CSC) that treats more than 500 patients with acute stroke and performs more than 100 mechanical stroke thrombectomy procedures annually and is staffed by trained neurointerventional technique.
A sample of 228 patients has been estimated to be necessary to demonstrate the utility of SEPs. They are going to be recruited from acute stroke patients gone under urgent thrombectomy in our center. Data of the patient is going to be register manually on paper and electronically with a statistical program (SPSS).
Medical treatment and mechanical thrombectomy workflow. Intravenous alteplase is given within 4.5 hours in eligible patients following a model ship or drip and ship model with a DTN target median time of less than 35 min. The target time from hospital arrival at the CSC to groin puncture is 80 minutes or less and from study baseline neuroimaging to first reperfusion is 90 minutes or less. MT is performed with stent retrievers or thrombus aspiration. The use of general anesthesia or conscious sedation is left at the discretion of the neurointerventional staff, but conscious sedation is preferred over intubation (30,31). BP and vital signs are continuously monitored during the procedure. Patients are admitted at acute stroke units (or ICU if needed) and treated following the European Stroke Organization ESO guidelines(32)
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
- •Acute stroke with a demonstrated occlusion in the anterior circulation (M1 or M2 segment of middle cerebral artery with or without ipsilateral internal carotid artery (ICA)significant stenosis or occlusion diagnosed by CT angiography (CTA) or angio-MRI) undergoing urgent thrombectomy procedure.
- •Prestroke functional independence of 2 or less on the modified Rankin scale (ranging from 0 [no symptoms] to 6 [death]),
- •Baseline score of at least 6 points on the National Institutes of Health Stroke Scale (NIHSS), which ranges from 0 to 42, with higher values indicating more severe deficit.
排除标准
- •Evidence by imaging of a large ischemic core, as indicated by an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of less than 5 on computed tomography (CT) without the use of contrast material or a score of less than 4 on diffusion-weighted magnetic resonance imaging (MRI) (ASPECTS values range from 0 to 10, with higher values indicating less infarct burden). These cutoff values of the ischemic core have been selected in agreement with the treatment effect showed in the HERMES trial meta-analysis collaboration (Presented at the International Stroke Conference, Houston, 2017).
- •Well-documented history of neuromuscular disorders, stroke or central nervous system tumors that could interfere in the SEPs assessment.
结局指标
主要结局
Functional independence at 7 days or discharge
时间窗: Baseline to 7 days or the day of discharge from hospital if it happens before the 7th day
The primary outcome is the functional independence at 7 days or discharge, defined by the modified Rankin scale score 0- 2. This early and more feasible outcome has a very high correlation with functional dependence at 90 days (Davalos A et al. Lancet Neurol 2017). Local certified assessors who are unaware of the SEPs monitoring findings evaluate the primary outcome variable in each patient by means of a structured interview.
次要结局
- Functional independence at 90 days from the stroke(Baseline to 90 days)
- Neurologic improvement(Baseline to 24 hours)
- Clinical status(Baseline to 7 days or the day of discharge from hospital if it happens before the 7th day)
- Infarct volume at 24 hours(Baseline to 24 hours)
- Postprocedural revascularization(Baseline to end of thrombectomy treatment, an average of 1 hour)
- Early dramatic response to treatment(Baseline to 24 hours)
- Vessel revascularization(Baseline to 24 hours)
- Perfusion recovery(Baseline to end of thrombectomy treatment, an average of 1 hour)