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Management of Poststroke Hyperglycemia : Results of the TEXAIS Randomized Clinical Trial
Bladin, Christopher Wah Cheung, Ngai Dewey, Helen M. Churilov, Leonid Middleton, Sandra Jane Thijs, Vincent Ekinci, Elif I Levi, Chris Lindley, Richard Donnan, Geoffrey
Bladin, Christopher
Wah Cheung, Ngai
Dewey, Helen M.
Churilov, Leonid
Middleton, Sandra Jane
Thijs, Vincent
Ekinci, Elif I
Levi, Chris
Lindley, Richard
Donnan, Geoffrey
Author
Bladin, Christopher
Wah Cheung, Ngai
Dewey, Helen M.
Churilov, Leonid
Middleton, Sandra Jane
Thijs, Vincent
Ekinci, Elif I
Levi, Chris
Lindley, Richard
Donnan, Geoffrey
Parsons, Mark William
Meretoja, Atte
Tiainen, Marjaana
Choi, Philip M C
Cordato, Dennis
Brown, Helen
Campbell, Bruce C V
Davis, Stephen
Cloud, Geoffrey
Grimley, Rohan
Lee-Archer, Matthew
Ghia, Darshan
Sanders, Lauren
Markus, Romesh
Muller, Claire
Salvaris, Patrick
Wu, Teddy
Fink, John
Wah Cheung, Ngai
Dewey, Helen M.
Churilov, Leonid
Middleton, Sandra Jane
Thijs, Vincent
Ekinci, Elif I
Levi, Chris
Lindley, Richard
Donnan, Geoffrey
Parsons, Mark William
Meretoja, Atte
Tiainen, Marjaana
Choi, Philip M C
Cordato, Dennis
Brown, Helen
Campbell, Bruce C V
Davis, Stephen
Cloud, Geoffrey
Grimley, Rohan
Lee-Archer, Matthew
Ghia, Darshan
Sanders, Lauren
Markus, Romesh
Muller, Claire
Salvaris, Patrick
Wu, Teddy
Fink, John
Abstract
Hyperglycemia in acute ischemic stroke reduces the efficacy of stroke thrombolysis and thrombectomy, with worse clinical outcomes. Insulin-based therapies are difficult to implement and may cause hypoglycemia. We investigated whether exenatide, a GLP-1 (glucagon-like peptide-1) receptor agonist, would improve stroke outcomes, and control poststroke hyperglycemia with minimal hypoglycemia.
Methods:The TEXAIS trial (Treatment With Exenatide in Acute Ischemic Stroke) was an international, multicenter, phase 2 prospective randomized clinical trial (PROBE [Prospective Randomized Open Blinded End-Point] design) enrolling adult patients with acute ischemic stroke ≤9 hours of stroke onset to receive exenatide (5 µg BID subcutaneous injection) or standard care for 5 days, or until hospital discharge (whichever sooner). The primary outcome (intention to treat) was the proportion of patients with ≥8-point improvement in National Institutes of Health Stroke Scale score (or National Institutes of Health Stroke Scale scores 0–1) at 7 days poststroke. Safety outcomes included death, episodes of hyperglycemia, hypoglycemia, and adverse event.
Results:From April 2016 to June 2021, 350 patients were randomized (exenatide, n=177, standard care, n=173). Median age, 71 years (interquartile range, 62–79), median National Institutes of Health Stroke Scale score, 4 (interquartile range, 2–8). Planned recruitment (n=528) was stopped early due to COVID-19 disruptions and funding constraints. The primary outcome was achieved in 97 of 171 (56.7%) in the standard care group versus 104 of 170 (61.2%) in the exenatide group (adjusted odds ratio, 1.22 [95% CI, 0.79–1.88]; P=0.38). No differences in secondary outcomes were observed. The per-patient mean daily frequency of hyperglycemia was significantly less in the exenatide group across all quartiles. No episodes of hypoglycemia were recorded over the treatment period. Adverse events of mild nausea and vomiting occurred in 6 (3.5%) exenatide patients versus 0 (0%) standard care with no withdrawal.
Conclusions:Treatment with exenatide did not reduce neurological impairment at 7 days in patients with acute ischemic stroke. Exenatide did significantly reduce the frequency of hyperglycemic events, without hypoglycemia, and was safe to use. Larger acute stroke trials using GLP-1 agonists such as exenatide should be considered.
Registration:URL: www.australianclinicaltrials.gov.au; Unique identifier: ACTRN12617000409370. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03287076.
Keywords
Exenatide, Hyperglycemia, Ischemic stroke, Stroke, Thrombectomy
Date
2023
Type
Journal article
Journal
Book
Volume
54
Issue
12
Page Range
2962-2971
Article Number
ACU Department
Nursing Research Institute
Faculty of Health Sciences
Faculty of Health Sciences
Collections
Relation URI
Event URL
Open Access Status
Published as ‘gold’ (paid) open access
License
CC BY 4.0
File Access
Open
Notes
The TEXAIS (Treatment With Exenatide in Acute Ischemic Stroke) was supported by research grant 1126070 from the National Health and Medical Research Council of Australia. The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Material support from Medtronic in the use of Medtronic iPro2 Professional Continuous Glucose Monitors.
© 2023 The Authors. Stroke is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.
© 2023 The Authors. Stroke is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.