1. Management of Poststroke Hyperglycemia: Results of the TEXAIS Randomized Clinical Trial.
- Author
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Bladin CF, Wah Cheung N, Dewey HM, Churilov L, Middleton S, Thijs V, Ekinci E, Levi CR, Lindley R, Donnan GA, Parsons MW, Meretoja A, Tiainen M, Choi PMC, Cordato D, Brown H, Campbell BCV, Davis SM, Cloud G, Grimley R, Lee-Archer M, Ghia D, Sanders L, Markus R, Muller C, Salvaris P, Wu T, and Fink J
- Subjects
- Adult, Humans, Aged, Exenatide therapeutic use, Prospective Studies, Glucagon-Like Peptide 1 therapeutic use, Treatment Outcome, Ischemic Stroke complications, Stroke complications, Stroke drug therapy, Hyperglycemia drug therapy, Hyperglycemia complications, Hypoglycemia complications
- Abstract
Background: 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., Competing Interests: Disclosures The authors declare no competing interests for the TEXAIS trial (Treatment With Exenatide in Acute Ischemic Stroke). Dr Grimley declares travel support from Boehringer Ingleheim. Dr Meretoja declares research funding support from Monash University. Dr Davis declares research funding support from Medtronic, Amgen, CSL Behring, AstraZeneca, and Boehringer Ingelheim. Dr Ekinci is a consultant in Eli Lilly, Australia and reports research funding support from Eli Lilly, Australia, Amgen, Boehringer Ingelheim, and Bayer. Dr Thijs is a consultant in Bayer, Boehringer Ingelheim, Medtronic, and Novo Nordisk. Dr Lee-Archer declares research funding support from Clifford Craig Foundation. The other authors report no conflicts.
- Published
- 2023
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