SEdation Versus General Anesthesia for Endovascular Therapy in Acute Ischemic Stroke (SEGA)

SEGA - SEdation Versus General Anesthesia for Endovascular Therapy in Acute Ischemic Stroke - a Randomized Comparative Effectiveness Trial.

Objectives:

This study aims to estimate overall treatment benefit (improvement in disability) among acute ischemic stroke patients that are randomized to General Anesthesia (GA) compared with Sedation (CS) during endovascular therapy. Assess safety (as measured by incidence of symptomatic intracranial hemorrhage); rates of Endovascular therapy (EVT) procedural complications, reperfusion; and quality of life.

Hypothesis:

GA during EVT for acute ischemic stroke improves functional outcomes at 90 days compared to sedation.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Drug: Sedation; Procedure: Intra-arterial Thrombectomy; Drug: General Anesthesia (GA)

• Study Type: Interventional
• Enrollment (Actual): 260
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Peng Roc Chen, MD; Phone Number: 713-486-8016; Email: peng.r.chen@uth.tmc.edu
• Study Contact Backup: Name: Eddie Aguilar, BA; Phone Number: 713-486-7764; Email: Eddie.Aguilar@uth.tmc.edu

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University College of Medicine
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Kentucky
    • Louisville, Kentucky, United States, 48150
      • Henry Ford Health System
  • New York
    • Rochester, New York, United States, 14617
      • Rochester Regional Health
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Health
    • Philadelphia, Pennsylvania, United States, 19122
      • Temple University
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77024
      • Memorial Hermann Hospital System - Memorial City Medical Center
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center Houston with Memorial Hermann Hospital System - The Medical Center
    • The Woodlands, Texas, United States, 77380
      • Memorial Hermann Hospital System - The Woodlands Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Acute ischemic stroke due to large intracranial vessel occlusion demonstrated on CT-angiography in the following anterior circulation locations that will be treated by endovascular therapy (EVT):

   1. Internal Carotid Artery (terminal "T" or "L-type"- occlusion)
   2. Middle Cerebral Artery (MCA) M1 or proximal M2

   3. Anterior Cerebral Artery (ACA) A1 or proximal A2

      • Patients who receive IV-tPA thrombolysis are eligible provided the drug was delivered within 4.5 hours of stroke onset or last seen normal and in accordance with local hospital standard of care.
2. Ages 18-90.
3. National Institute of Health Stroke Scale (NIHSS) score 6-30
4. Time of from stroke symptom onset of last seen normal to start of EVT (defined as groin puncture) ≤ 16 hours.

5. Limited infarct core, as defined below and adapted from the 2018 American Heart Association guidelines

   1. For patients presenting ≤ 6 hours from time of symptom onset or last seen normal, Alberta Stroke Program Early Computed Tomography Score (ASPECTS) ≥ 6
   2. For patients presenting > 6 hours and ≤ 16 hours from time of symptom onset or last seen normal, they must satisfy EITHER ONE of the two following criteria:

   i. Ischemic core by CT Perfusion or MRI/MR Perfusion < 70 mL, a ratio of volume of penumbral tissue to infarct core of ≥ 1.8, and and absolute volume of penumbral tissue of ≥ 15 mL OR ii. For patients with NIHSS ≥ 10, infarct core of < 31 mL by CT Perfusion or MRI; For patients with NIHSS ≥ 20, infarct core < 51 mL.

6. Subject willing/able to return for protocol required follow up visits.
7. No significant pre-stroke disability (modified Rankin Score must be ≤ 2).
8. Females of childbearing potential must have a negative serum or urine pregnancy test.
9. Patient or patient's legally authorized representative has given Informed Consent according to Good Clinical Practices (GCP) and/or local IRB policies.

Exclusion Criteria:

1. Coma on admission (Glasgow Coma Scale <8), need for intubation upon ED arrival, or transferred patients who present previously intubated.
2. Severe agitation or seizures on admission that preclude safe vascular access.
3. Loss of airway protective reflexes and/or vomiting on admission.
4. Predicted or known difficult airway.
5. Pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, e.g. dementia.
6. Presumed septic embolus, or suspicion of bacterial endocarditis
7. Currently participating or has participated in any investigational drug or device study within 30 days.
8. Inability to follow-up for 90-day assessment.
9. Known history of allergy to anesthesia drugs.
10. Known history or family history of malignant hyperthermia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sedation; The protocol does not specify a particular combination of drugs that must be used for sedation. The choice of specific drugs and dosages for achieving sedation will be up to the anesthesiologist.	Drug: Sedation; The protocol does not specify a particular combination of drugs that must be used for sedation. The most common drugs utilized for sedation and wide dosing ranges are included in the protocol (i.e., sedation will be provided under the supervision of an anesthesiologist and may use a combination of fentanyl, midazolam, dexmedetomidine infusion (with or without loading dose), and/or low-dose propofol by intermittent bolus or infusion); however, the choice of specific drugs and dosages for achieving conscious sedation or general anesthesia will not be specified by the protocol but will be up to the anesthesiologist.; Procedure: Intra-arterial Thrombectomy; The first line therapeutic embolectomy device should be a stent retriever. Additional Endovascular therapies including, but not limited to, intra- or extracranial angioplasty ± stenting; antithrombotics (oral, IV or IA antiplatelets or anticoagulants) intra-arterial thrombolytics; are left to the decision of the local treatment team.; Other Names: Endovascular Therapy
Active Comparator: General Anesthesia; The protocol does not specify a particular combination of drugs that must be used for general anesthesia. The choice of specific drugs and dosages for achieving general anesthesia will be up to the anesthesiologist.	Procedure: Intra-arterial Thrombectomy; The first line therapeutic embolectomy device should be a stent retriever. Additional Endovascular therapies including, but not limited to, intra- or extracranial angioplasty ± stenting; antithrombotics (oral, IV or IA antiplatelets or anticoagulants) intra-arterial thrombolytics; are left to the decision of the local treatment team.; Other Names: Endovascular Therapy; Drug: General Anesthesia (GA); The protocol doesn't specify drugs that must be used for GA, the choice of drugs and dosages for achieving general anesthesia will not be specified by the protocol but will be up to the anesthesiologist. The most common drugs utilized for GA and wide dosing ranges included in the protocol are (GA will be provided under the supervision of an anesthesiologist and induction of anesthesia may be achieved with propofol and/or etomidate; muscle paralysis may be achieved with succinylcholine or non-depolarizing paralytic (rocuronium or vecuronium); and adjuvant lidocaine and fentanyl; if intravenous maintenance of anesthesia is used, it may be achieved by propofol infusion at 50 to 150 mcg/kg/min with redosing of non-depolarizing paralytic and fentanyl as needed; if inhalational maintenance of anesthesia is used it will be achieved with sevoflurane 1% to 2% or desflurane 3% to 6% end-tidal concentration with redosing of non-depolarizing paralytic and fentanyl as needed)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
modified Rankin Scale (mRS)	Comparison of independent clinical outcome as measured by the modified Rankin Scale (mRS) at 90 days (scores 5 and 6 combined) among patients randomized to GA versus Sedation assessed by study personnel blinded to treatment.	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dichotomized modified Rankin Scale (mRS)	Dichotomized modified Rankin Scale (mRS) at 90 days (0-2 vs 3-6) adjusted for stratification variable	90 days
Rates of recanalization	Rates of recanalization using modified TICI scores	post procedure within 6 hours
National Institute of Health Stroke Scale (NIHSS) scale	Early clinical improvement measured by difference NIHSS scale	24-36 hours post procedure
modified Rankin Scale (mRS)	Independent functional outcome in General Anesthesia patients treated with inhalational vs. intravenous medications.	90 days
Quality of life as assessed by the European Quality of Life-5 Dimensions (EQ-5D) instrument		90 days
Incidence of symptomatic intracerebral hemorrhage	Safety measured by incidence of symptomatic intracerebral hemorrhage	18-36 hours post procedure
Incidence of mortality	Safety measured by incidence of mortality	18-36 hours post procedure
Incidence of device related complications	Safety measured by incidence of device related complications	18-36 hours post procedure

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: Stryker Neurovascular
• Investigators: Principal Investigator: Sean Savitz, MD, The University of Texas Health Science Center, Houston; Study Chair: Peng Roc Chen, MD, The University of Texas Health Science Center, Houston; Principal Investigator: Carlos Artime, MD, The University of Texas Health Science Center, Houston; Principal Investigator: Sunil Sheth, MD, The University of Texas Health Science Center, Houston; Principal Investigator: Claudia Pedroza, PhD, The University of Texas Health Science Center, Houston; Principal Investigator: Andrew Barreto, MD, The University of Texas Health Science Center, Houston

Publications and helpful links

General Publications

• Tosello R, Riera R, Tosello G, Clezar CN, Amorim JE, Vasconcelos V, Joao BB, Flumignan RL. Type of anaesthesia for acute ischaemic stroke endovascular treatment. Cochrane Database Syst Rev. 2022 Jul 20;7(7):CD013690. doi: 10.1002/14651858.CD013690.pub2.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2018
• Primary Completion (Actual): April 22, 2023
• Study Completion (Actual): April 22, 2023

Study Registration Dates

• First Submitted: August 16, 2017
• First Submitted That Met QC Criteria: August 23, 2017
• First Posted (Actual): August 28, 2017

Study Record Updates

• Last Update Posted (Actual): May 12, 2023
• Last Update Submitted That Met QC Criteria: May 10, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Acute stroke; Cerebral Stroke
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics
• Other Study ID Numbers: HSC-MS-17-0436

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No