Glucagon-like Peptide 1 Receptor Agonist in Acute Large Vessel Occlusion Stroke Treated by Reperfusion Therapies

Status

Completed

Phase

Phase 2

Enrollment

140 participants (actual)

Sponsor

Chinese University of Hong Kong · Other

Design

Randomized · Open label (no masking)

Countries

2 countries

China, Hong Kong

Start

1 Aug 2023

Primary completion

25 Oct 2024

Completion

25 Oct 2024

First posted

27 Jun 2023

Last update posted

7 Mar 2025

Conditions

Stroke · Stroke, Acute · Stroke, Ischemic · Brain Diseases

Endovascular thrombectomy (EVT) is a highly effective therapy for acute ischemic stroke with large vessel occlusion (LVO). EVT was proven efficacious in selected patients with symptoms onset or last-known-well time of up to 24 hours. With a number-needed-to-treat (NNT) of 2.3-2.8 to achieve functional independence, EVT had become the current state-of-the-art treatment for ischemic stroke with LVO. Nevertheless, more than half of LVO strokes suffered from functional dependence or death despite EVT. Futile EVTs were contributed by peri-procedural malignant brain edema (MBE) and symptomatic intracranial hemorrhage (sICH). Studies suggested that 26.9% of EVTs were complicated by MBE, whereas sICH was present in 6-9% of LVO patients who received EVT. The fundamental pathophysiology of MBE and sICH is blood-brain-barrier (BBB) disruption secondary to ischemia, mechanical and reperfusion injury. These pathological processes can result in increased tissue permeability, excess production of oxygen free radicals and inflammatory response that eventually lead to hemorrhage and edema. Poor collateral circulation, proximal LVOs, intravenous thrombolysis, blood pressure and glucose fluctuation had all been implicated to in MBE and sICH. However, these risk factors were either unmodifiable or not shown to improve EVT outcomes. The preliminary results of a recent randomized trial even suggested harmful effects of intensive blood pressure following EVT. With indications of EVT are expanding to patients with prolonged ischemia and large ischemic cores, enhancing BBB and neuronal tolerance to ischemia and reperfusion therapies may hugely impact on EVT outcomes. Recent animal models have shown that glucagon-like peptide peptide-1 receptor agonists (GLP-1RA) significantly reduced infarct volume and neurological deficits following temporary or permanent middle cerebral artery occlusion. These effects were likely due to the anti-oxidant, anti-inflammatory and anti-apoptotic properties of GLP-1RA that protected BBB integrity and ischemic neurons during induced LVO and/or reperfusion. Investigator hypothesizes that compared to standard reperfusion strategies, administration of GLP-1RA in LVO patients who receive EVT may prevent the development of MBE and sICH, and improve neurological outcomes. In this randomized, open-label pilot study, investigator aims to determine the effect of semaglutide, a GLP-1RA, on the radiological and clinical outcomes in LVO patients undergoing EVT.

• Active comparator

  Semaglutide Group

  Prescribe study drug: Patients randomized into the semaglutide group will receive 0.5mg subcutaneous injection of the drug before or during EVT, and 7 days after the procedure. i.e. semaglutide group will receive a total of 2 injections.

• No intervention

  Standard of care

  Standard medical therapy

1. Change of Modified Rankin Score

   Time frame · Day 90

   Registry description

   Change of Modified Rankin Score to measure degree of disability/dependence. Scores 0-2 is considered good outcome, while scores 3-6 is considered poor outcome.

2. Composite Safety Outcome

   Time frame · Day 90

   Registry description

   Composite of Death, Intracranial Hemorrhage (ICH) and Malignant Brain Edema (MBE)