Stroke

Learn about clinical trials related to stroke taking place at UCLA on clinicaltrials.gov >

In addition to those trials, UCLA is also leading the SEACOAST trial below:

SEACOAST 1

ClinicalTrials.gov ID: NCT03737786

SEdAtion with COllAteral Support in endovascular Therapy for acute ischemic stroke 1: a randomized controlled clinical trial

Design Hypothesis Criteria Protocol For Patients Contacts

Information for physicians

Study overview in lay language:
Ischemic stroke is a leading cause of disability and death worldwide. Approximately one third of all ischemic strokes are due to blockage of large brain vessel resulting in diminished flow to the brain and potentially devastating outcome. The currently accepted treatment of this type of stroke is a minimally invasive procedure called thrombectomy. The goal of this procedure is to restore blood flow to the brain as fast as possible and thereby reverse the patient’s deficits. The procedure involves reaching the occluded brain vessel and removing the culprit clot by advancing a catheter through one of the peripheral arteries (usually the femoral artery). However, thrombectomy is only beneficial if done rapidly and only in patients with viable brain tissue. The main factor determining brain tissue viability and salvageability in setting of acute stroke due to large vessel occlusion is collateral circulation. As such, patients who are able to sustain brain perfusion vial collateral circulation benefit the most from thrombectomy. The procedure can be associated with substantial discomfort and patient movement, and it requires patients to be sedated. There are two types of sedations: 1) conscious sedation (CS), during which the patients is partially sedated but still awake, or 2) general anesthesia (GA), during which the patient is completely sedated and paralyzed with a breathing tube for assisted mechanical ventilation. The existing knowledge regarding the choice between these two methods of sedation is controversial and therefore they are both acceptable options in current practice. While GA completely eliminates patient movement and pain, it may be associated with potential delays, complications from mechanical ventilation, and overall higher cost. However, one potential advantage of GA over CS is to improve collateral circulation by increasing blood flow to the brain through tight control of important physiologic parameters such as blood pressure and CO2 levels in the body. CO2 is a well-known factor that directly impacts brain flow to the brain and can be easily regulated through mechanical ventilation in setting of GA. In this study, we propose to investigate the effect of two distinct GA strategies upon collateral circulation and clinical outcome: a) GA with normal CO2 levels (normocarbia) and b) GA with slightly elevated CO2 levels (mild hypercarbia). We hypothesize that patients with acute ischemic stroke due to large vessel occlusion who undergo thrombectomy under GA mild hypercarbia will have better collateral flow and better clinical outcome as compared with GA with normocarbia. The results of this study will allow us to select the better GA strategy to test against CS in subsequent final phase and ultimately determine the best possible sedation strategy for acute stroke thrombectomy.

Study overview
The SEACOAST investigators plan a series of two trials (Figure 1). The current protocol is for SEACOAST 1, a biomarker efficacy trial to determine the most promising form of general anesthesia (GA) to advance to a pivotal trial against conscious sedation with monitored anesthesia care (MAC). 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. SEACOAST 1 is to be conducted in Ronald Reagan UCLA Medical Center and Santa Monica UCLA 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).

Study design

SEACOAST 1 is a prospective, randomized, blinded endpoint trial comparing collateral vigor and clinical outcomes, focusing on two distinct sedation strategies:
A. General anesthesia with mild hypercarbia (GAH) during the sedation up until full revascularization versus
B. General anesthesia with normocarbia (GAN) during the sedation up until full revascularization

Study Hypothesis

We hypothesize that GA with strict blood pressure support and controlled mild hypercarbia (GAH) will lead to better neurologic outcome as compared to MAC with strict blood pressure support. This study will use a two-phase strategy using cerebral collateral circulation as a highly informative biomarker in the initial phase 2 to determine if a non-standard GA approach (GAH) shows evidence of a differential, likely beneficial biologic effect as compared with a standard GA approach (GAN- GA with normocarbia). If there is biomarker evidence suggesting potential differential benefit of GAH, we will proceed to test GAH against MAC in the subsequent pivotal phase 3 trial using clinical end points. If there is no biomarker evidence suggesting potential differential benefit of GAH, we will proceed to test GAN against MAC in the subsequent pivotal phase 3 trial using clinical end points.

A. Primary endpoint hypothesis:

GAH will lead to better collateral cerebral circulation as compared to GAN during the procedure

The primary endpoint analyzed to test this hypothesis is collateral robustness at measured at catheter angiography on the ordinal 0-4 ASITN scale.

B. Secondary endpoint hypothesis:

GAH will lead to better clinical outcome at 90 days

The endpoints analyzed to test this hypothesis is difference in::

90 day global disability assessed via the blinded evaluation of modified Rankin scale (mRS)
Functional independence as defined by modified Rankin Scale (mRS) score 2 at 90 days
NIH Stroke Scale score at: 24 hrs, 30, and 90 days post randomization

C. Other physiologic, technical, and safety endpoints will include:

Physiologic endpoints:
- Volume of cerebral infarction as measured by a CT or MRI scan at 24 ±6hrs post randomization by RAPID software imaging
- Growth of cerebral infarction defined by % difference in volume between baseline pre-intervention CT or MRI and 24 ±6hrs CT or MRI post randomization RAPID software imaging
Technical endpoints :
- Arterial revascularization measured by TICI scoring at the end of the procedure
- Door to first intracranial device placement time interval
- Number of thrombectomy attempts
- Procedural duration measured by fluoroscopy time
Safety endpoints:
- Symptomatic hemorrhagic transformation (ECASS 3 definition)
- All radiologic intracranial hemorrhage
- All-cause mortality through 3 months
- Pneumonia rates during first 7 days
- Hypotension rates during first 24 hours

Patient Selection Criteria:

Inclusion Criteria

Age 18-85
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 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

Clinical Exclusion Criteria:

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] < 30.
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

Neuroanesthesia protocol, focused on maintenance of baseline BP, avoidance of hypotension during induction, and targeted PCO2 levels (normocarbia or mild hypercarbia):

Anesthesia must not delay target initiation of procedure (groin puncture) of 90 min from ED arrival
Standard ASA monitoring: 5 lead ECG, end-tidal CO2 (ETCO2), Pulse oximeter, BP monitor, Body temperature per esophageal probe, ET gas analyser
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 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 iv TPA. *BP can be lowered to desired goal only after revascularization as deemed necessary by the neurointerventionalist
Induction with propofol or etomidate and rocuronium 1.2 mg/kg or succinylcholine
Etomidate has been proven to preserve hemodynamic stability during induction of general anesthesia even in sick, volume depleted patients. 49 47 The drug has the unique ability to spare vascular tone, myocardial contractility, and heart rate while rapidly achieving hypnotic state. When it comes to maintaining blood pressure at pre induction levels Etomidate is a far superior drug than Propofol particularly in patients with cardiovascular instability such as trauma, cardiac comorbidity, volume depletion, etc 50. Etomidate has become a logical choice for many anesthesiologists, intensivists, and ED providers in this patient population 51 52 One notable side effect of Etomidate is the temporary suppression of cortisol synthesis with ensuing lower cortisol plasma levels for up to 24 hours after administration of a single dose. However, no study has shown a definitive link between adrenal suppression caused by Etomidate and higher mortality or bad clinical outcome in non-septic patients.
Short acting vasoactive drugs (Phenylephrine, Ephedrine, Esmolol, Clevidipine) should be readily available to maintain BP in the predefined range throughout procedure. Phenylephrine drip recommended to maintain BP
Anesthesia maintenance with volatile anesthetic and fentanyl; doses to be titrated to BP per anesthesiologist
Qualitative end-tidal CO2 (ETCO2) measurement
Immediately upon groin puncture interventionalist will provide blood gas sample to test arterial C02
Normocarbia arm:
Controlled ventilation with PCO2 levels 40 (±5%)
Mild hypercarbia arm:
Controlled ventilation with PCO2 levels 50 (±5%)
Normalize PCO2 levels to 40 (±5%) immediately after adequate revascularization (TICI 2B)
Baseline arterial blood gas values for correlation/correction with PCO2 level detected on ETCO2 measurements
Mandatory extubation attempt within 60 minutes after procedure completion. Reasons for failed extubation should be documented

Information For Patients

What is this research study?

UCLA Ronald Reagan Medical Center (RRMC) has been selected to participate in the study sponsored by the Society of Vascular and Interventional Neurology (SVIN) called Sedation with Collateral Support in Endovascular Therapy for Acute Ischemic Stroke (SEACOAST). This trial is testing a specific method of sedation during a procedure called thrombectomy. This procedure has been established as a standard of care of treatment of acute ischemic stroke and is routinely performed at RRMC as well as many stroke centers in US and around the world. There are two types of accepted sedations for this procedure : 1) conscious sedation (CS), during which patients are partially sedated but still awake, or 2) general anesthesia (GA), during which patients are completely sedated and paralyzed with a breathing tube for assisted mechanical ventilation. The existing knowledge regarding the choice between these two methods of sedation is controversial and therefore they are both acceptable options in current practice. This trial is testing whether one specific type of non-standard type GA with mildly elevated carbon dioxide levels (CO2) is better than standard type of GA with normal CO2 levels. CO2 has been shown to improve blood flow to the brain and may help patients with acute ischemic stroke.

Who will be enrolled in the study?

If you are having symptoms of a stroke and meet the study criteria, you may be enrolled in the SEACOAST trial. The UCLA stroke team who evaluate all patients with acute strokes in the emergency department (ED) are trained to identify potential study patients by following very strict criteria. If you are having a stroke and you are eligible to receive thrombectomy, you may be eligible for the study.

If you are able to make decisions for yourself, you will be asked to read a study consent form, have any questions answered by a study doctor, and decide whether or not you would like to enroll in the study.

You may be unable to make a decision for yourself because the stroke has impaired your ability to use language or to think. If this happens and the study doctor finds that you meet all study criteria, you may still be enrolled in the study. The study doctor will still try to determine your feelings about the study and will not enroll you if you seem to not want to participate.

Will my family help determine if I participate in the study?

You will only be enrolled in the study if family, friends, coworkers or other individuals who know you are with you at the time. The study doctor will explain the study to them and give family an opportunity to decline your participation.

If I participate, what is involved in the study?

You will receive all the standard and routine tests and treatments normally received by stroke patients.
You will be randomly assigned to either receive standard GA or non-standard GA with mildly elevated carbon dioxide levels (CO2) . Half of the patients receive GA with normal CO2 levels the other half will receive GA with mildly elevated CO2 levels. You will receive either method of sedation during the procedure, which typically lasts 1-2 hours.
You will receive routine clinical and imaging assessment as part of the standard of care for all patients with acute stroke
You will answer questions by phone in about 30 and 90 days to report how you are doing in activities of daily living (5 minute phone interview).
You will have a 40 minute follow-up visit in about 90 days to undergo a brief (5 minute) neurologic exam and to answer questions regarding activities of your daily living, attitudes, and motor and communication function (30 minutes).

Study Results: Pending

Contacts:

Radoslav Raychev (Study Principal Investigator):
email: [email protected]
tel: 310-794-6379

Avila Gilda (Study Coordinator)
email: [email protected]
tel: 310-825-1806

Study Team:
Radoslav Raychev: Principal Investigator (Neurology)
Natalie Moreland: Co-Principal Investigator (Anesthesiology)
Clinical Research Coordinator: Gilda Avila

Study Steering Committee:
Radoslav Raychev (Neurology)
Natalie Moreland (Anesthesiology)
Jeffery Saver, MD (Neurology)
Reza Jahan, MD (Interventional Neuroradiology)
Keren Ziv, MD (Anesthesiology)
Barbara M Van de Wiele, MD (Anesthesiology)

Data Safety Monitoring Board:
Ameer Hassan, MD (Interventional and Stroke Neurology)
Director, Endovascular Surgical Neuroradiology, Neurocritical care, and Clinical Neuroscience research at Valley Baptist Medical Center Harlingen, Texas
Dimiter Arnaudov MD (Neuro Anesthesiology)
Department of Anesthesiology, USC
Bill Mack, MD (Interventional Neuroradiology/Neurointerventional Surgery)
Professor of Neurological Surgery (Clinical Scholar); Director, Neurointerventional Program, Keck Hospital of USC; Director, Neurosurgery Ambulatory Services, Keck Medical Center of USC; Vice Chair, Academic Affairs
Nerses Sanossian, MD (Stroke Neurology, Neurocritical Care)
Associate Professor of Neurology (Clinical Scholar)
Director, Roxanna Todd Hodges Stroke Program
USC Department of Neurology
Fernando Vinuela, MD (Interventional Neuroradiology)
Professor Emeritus, UCLA Department of Radiology