Title : SEACOAST 1 SEdAtion With COllAteral Support in Endovascular Therapy for Acute Ischemic Stroke 1: a Randomized Controlled Phase 2B Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 90
- 试验地点
- 2
- 主要终点
- Modified Angiographic collateral circulation assessed by blinded core lab
研究概览
简要总结
SEACOAST 1 is a prospective, randomized, blinded endpoint trial comparing collateral vigor and clinical outcomes, with different forms of GA in patients with acute ischemic stroke due to anterior circulation large vessel occlusion (LVO) undergoing mechanical thrombectomy. The study compares GA with normocarbia (GAN) versus GA with mild hypercarbia (GAH), with a primary outcome of collateral robustness at measured at catheter angiography and clinical efficacy as secondary outcome. It is anticipated that the SEACOAST 1 will be followed by a larger, pivotal trial, SEACOAST 2, with primary clinical endpoints, in which the best method of GA identified in SEACOAST 1 is compared with the alternative strategy of anesthesia care (MAC) with minimal or no sedation. The current study focuses uppn SEACOAST 1, which is to be conducted in University of California, Los Angeles Ronald Reagan Medical Center and Santa Monica Medical Center. All acute stroke patients who arrive to one of these two stroke centers and are deemed eligible for thrombectomy will be considered for the proposed study. Physician-investigators will determine study eligibility. Informed consent to participate in the study will be obtained from legally authorized representatives or competent patients. For non-competent patients without on-scene legally authorize representatives, the consent process will utilize enrollment in emergency circumstances with exemption of informed consent (EFIC).
详细描述
Study design:
SEACOAST 1 is a prospective, randomized, blinded endpoint trial comparing collateral vigor and clinical outcomes, focusing on two distinct sedation strategies:
- General anesthesia with mild hypercarbia (GAH) during the sedation up until full revascularization versus
- General anesthesia with normocarbia (GAN) during the sedation up until full revascularization
Neuroanesthesia protocol, focused on maintenance of baseline BP, avoidance of hypotension during induction, and targeted partial pressure of carbon monoxide (PCO2) levels (normocarbia or mild hypercarbia):
- Anesthesia must not delay target initiation of procedure (groin puncture) of 90 min from ED arrival
- Standard American Society of Anesthesiologists (ASA) monitoring: 5 lead ECG, end-tidal CO2 (ETCO2), Pulse oximeter, BP monitor, Body temperature per esophageal probe, ET gas analyser
- Neuromuscular block (NMB) monitor for depth of neuromuscular blockade
- Arterial line placement is encouraged if it can be inserted within 5 min. Otherwise noninvasive BP per cuff. If arterial line has not been placed prior to induction monitor noninvasive blood pressure (NIBP) every 1 min per cuff until arterial line becomes available.
- BP goals - keep at baseline with goal of no more than 10% drop (last recorded BP prior to induction) and cannot exceed 185/105 if patients received intravenous tissue plasminogen activator (IV TPA).
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)
入排标准
- 年龄范围
- 18 Years 至 110 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •NIHSS ≥ 6 within 0-16h or NIHSS ≥ 10 within 16-24h
- •Anterior circulation large vessel occlusion (ICA, M1, M2)
- •ASPECTS score ≥ 6 within the first 6h, or DEFUSE trial imaging criteria within 6-16h; or DAWN trial clinical/imaging mismatch criteria within 16-24h
- •Premorbid modified Rankin Scale (mRS) 0-2
- •Patient deemed candidate for mechanical thrombectomy with anticipated groin puncture within 24 hours of last known well and within 90 min of ED arrival
排除标准
- •Intubation in ED prior to anesthesiologist evaluation, or intubation for any other medical reason other than planned thrombectomy
- •Rapid neurological improvement, suggestive of revascularization
- •Known serious sensitivity to radiographic contrast agents.
- •Current participation in another investigational drug or device treatment study.
- •Renal Failure as defined by a serum creatinine > 2.0 mg/dl (or 176.8 μmol/l) or Glomerular Filtration Rate [GFR] <
- •Subject who requires hemodialysis or peritoneal dialysis, or who have a contraindication to an angiogram for whatever reason.
- •Life expectancy of less than 90 days.
- •Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT or MRI scan is normal
- •Subject with a co-morbid disease or condition that would confound the neurological and functional evaluations or compromise survival or ability to complete follow up assessments.
- •Subject currently uses or has a recent history of illicit drug(s) or abuses alcohol (defined as regular or daily consumption of more than 4 alcoholic drinks per day.
- •Septic or cardiogenic shock with severe life-threatening hypotension
- •Imaging Exclusion Criteria:
- •Computed tomography (CT) or Magnetic Resonance Imaging (MRI) evidence of acute intracranial hemorrhage on presentation.
- •CT or MRI evidence of mass effect or intracranial tumor (except small meningioma).
- •CT showing hypodensity or MRI showing hyperintensity involving greater than 1/3 of the middle cerebral artery (MCA) territory (or in other territories, >100 cc of tissue) on presentation.
- •Baseline non contrast CT or DWI MRI evidence of a moderate/large core defined as extensive early ischemic changes of Alberta Stroke Program Early CT score (ASPECTS) < 6
- •CT or MRI evidence that ischemia is not in anterior circulation distribution.
- •Imaging evidence that suggests, in the opinion of the investigator, the subject is not appropriate for mechanical thrombectomy intervention (e.g., inability to navigate to target lesion, moderate/large infarct with poor collateral circulation, etc.).
- •Anesthesia exclusion criteria (relative):
- •History of Malignant Hyperthermia
- •History of allergic reaction/anaphylaxis to anesthetic drugs
- •Inability to tolerate supine position (severe CHF)
- •Chronic O2 dependence or any other known pulmonary condition that might lead to difficult extubation and prolonged mechanical ventilation including known pulmonary hypertension
结局指标
主要结局
Modified Angiographic collateral circulation assessed by blinded core lab
时间窗: Immediately prior to revascularization
Modified American Society of Interventional and Therapeutic Neuroradiology (ASITN) grading scale is an ordinal 0-4 scale for angiographic collateral assessment. It runs from 0 (no collaterals) to 4 (excellent collaterals) as follows: 0: No visible collaterals to the ischemic site; 1: Slow collaterals to the periphery of the ischemic site with persistence of some defect; 2 (-): rapid collaterals to the periphery of the ischemic site with collateral filling in \<50% of the territory; 2 (+): rapid collaterals to the periphery of the ischemic site with collateral filling \> 50% of the territory; 3: Collaterals with slow but complete angiographic blood flow of the ischemic bed by the venous phase; 4: Complete and rapid collateral blood flow to the vascular bed in the entire ischemic territory by retrograde perfusion.
次要结局
- infarct growth assessed by blinded core lab(From the first brain imaging upon arrival to emergency department (ED) up to 72 hours after intervention)
- modified Rankin Scale assessed by a blinded investigator(90 days after intervention)
- safety endpoints (defined as any parenchymal hematoma (PH), subarachnoid hemorrhage (SAH), or intraventricular (IVH) associated with death, or worsening of National Institute of Health Stroke Scale score (NIHSS) by 4 or more within 24 hours)(from the end of thrombectoy procedure up to 24 hours after intervention)
- infarct growth assessed by blinded core lab(From the first brain imaging upon arrival to emergency department (ED) up to 72 hours after intervention)
- modified Rankin Scale assessed by a blinded investigator(90 days after intervention)
- safety endpoints (defined as any parenchymal hematoma (PH), subarachnoid hemorrhage (SAH), or intraventricular (IVH) associated with death, or worsening of National Institute of Health Stroke Scale score (NIHSS) by 4 or more within 24 hours)(from the end of thrombectoy procedure up to 24 hours after intervention)
研究者
Radoslav Raychev
Assistant Clinical Professor
University of California, Los Angeles