Glucagon-like Peptide-1 Receptor Agonists for Endovascular Stroke Thrombectomy (LEAST)

A Multicentre, Prospective, Randomized, Open-label, Blinded Endpoint, Pilot Clinical Trial Evaluating Subcutaneous Semaglutide in Patients With Acute Ischaemic Stroke Due to Anterior Circulation Large Vessel Occlusion Treated With Endovascular Thrombectomy

Endovascular thrombectomy (EVT) is a procedure that improves recovery for people who suffer from a stroke by removing blood clots from large blood vessels in the brain. However, even with this treatment, over half of the patients either pass away or are left with serious disabilities within three months. This is partly because, even in cases of a successful EVT, brain tissue damage continues to grow. Extent of brain damage is a major factor in how well a patient recovers. Studies in animals have shown that a drug called semaglutide might help protect the brain and improve recovery after a stroke. Semaglutide is currently used for the treatment of diabetes and obesity and is given as a weekly injection under the skin.

The investigators are hoping to test whether giving semaglutide to stroke patients undergoing EVT can improve their recovery. A very large study at many hospitals is needed to answer this question. The investigators are starting with a smaller study to gain information on whether it is possible to perform a larger definitive one, and if so, how best to plan for it. In this first step the investigators will study 100 patients with stroke who are scheduled for EVT in approximately 10 stroke centers across Canada. These patients will be randomly divided (like flipping a coin) into two groups: one will receive weekly semaglutide injections for 12 weeks, while the other will not receive the drug. The investigators will track how many patients agree to participate, how many stay in the study, and how well they follow the treatment plan. The investigators will also monitor the patients' recovery, overall health, and any side effects from the treatment. These results will provide important information to plan the larger study with the goal of reducing death rates and long-term disability in stroke patients undergoing EVT.

Study Overview

• Status: Not yet recruiting
• Conditions: Ischemic Stroke
• Intervention / Treatment: Drug: Semaglutide

Detailed Description

Background/Importance:

Endovascular thrombectomy (EVT) has substantially improved functional outcomes and decreased mortality in acute ischemic stroke patients with large vessel occlusions (LVOs). However, more than half of the patients die or have significant disability at 90 days after EVT. Studies suggest considerable infarct growth despite successful EVT and infarct volume predicts survival and functional outcome after EVT. There is an unmet need for interventions to reduce infarct growth and improve the functional outcomes of patients with an acute LVO who undergo EVT. Glucagon-Like Peptide-1 receptor agonists (GLP-1 RAs) have been suggested to decrease infarct growth and improve motor and sensory impairments in both diabetic and non-diabetic animal models of stroke. GLP-1 RAs also consistently decreased the risk of major adverse cardiovascular events (MACE), with the most profound effect in stroke prevention, in large-scale randomized clinical trials (RCTs) of patients with and without history of diabetes.

Research Aims:

The overall goal of this study is to test whether semaglutide can improve the functional outcomes of adults with acute ischemic stroke attributed to an intracranial LVO who are planned for treatment with EVT. We are performing a pilot trial to obtain the factual feasibility prerequisites essential for the planning, design, funding and execution of a subsequent main phase trial.

Methods:

Glucagon-like peptide-1 receptor agonists for Endovascular Stroke Thrombectomy (LEAST) is a multicentre, prospective, randomized, open label, blinded endpoint (PROBE) pilot clinical trial. LEAST will recruit a total of 100 adult patients scheduled to receive EVT at approximately 10 high-volume stroke research centres in Canada over 1.5 to 2 years. Participants fulfilling the inclusion and exclusion criteria will be randomly assigned up to 6 hours from the end of the EVT procedure, defined as the time of the last angiographic run, to either receive semaglutide (0.25 mg subcutaneous [SC] weekly for 4 weeks followed by 0.5 mg SC weekly for another 8 weeks) or to no semaglutide treatment.

Outcomes:

The primary feasibility endpoint is recruitment rate. Secondary feasibility endpoints include retention rates and medication compliance. Exploratory outcomes include: Proportion of participants with functional independence (mRS scores 2 or less) at 90±14 days; Absolute difference in the NIHSS scores between randomization and 36±12 hours; Functional outcome at day 7±2, assessed with the ordinal mRS scores; Proportion of participants with functional independence (mRS scores 2 or less) at day 7±2; Functional outcome at day 30±7, assessed with the ordinal mRS scores; Proportion of participants with functional independence (mRS scores 2 or less) at day 30±7; Functional outcome at 90±14 days, assessed with the ordinal mRS scores; Quality of life at 90±14 days, assessed with the EQ-5D-5L scale; Recurrent stroke (ischemic, hemorrhagic or uncertain) by 90±14 days; Occurrence of MACE (any stroke, myocardial infarction cardiovascular death) by 90±14 days.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jodi Miller, PhD; Phone Number: 905-521-2100; Email: least@phri.ca
• Study Contact Backup: Name: Amanda Taylor; Phone Number: 905-521-2100; Email: least@phri.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18 years or above on the date of randomization.
2. EVT for an LVO in the anterior circulation, defined as the intracranial segment of the internal carotid artery (ICA) and/or the M1 or proximal M2 segment of the middle cerebral artery (MCA).
3. National Institutes of Health Stroke Scale (NIHSS) ≥ 6 points at the time of randomization.
4. Pre-stroke modified Rankin Scale (mRS) 0 or 1.
5. Ability to randomize within 6 hours from the end of EVT.
6. Capable of giving signed informed consent either independently, or by a legally authorized representative (LAR).

Exclusion Criteria:

1. Pregnancy or breast-feeding.
2. Renal insufficiency (creatinine clearance < 30mL/min).
3. Cirrhosis or severe hepatic dysfunction, characterized by jaundice, encephalopathy or coagulopathy.
4. History of pancreatitis in the year prior to randomization or evidence of acute pancreatitis on randomization.
5. Active sepsis on randomization.
6. Cancer, regionally advanced or metastatic, or for which treatment had been administered within 6 months from randomization, or hematological cancer that is not in complete remission.
7. Any terminal medical condition with life expectancy of less than 3 months.
8. Personal or family history of medullary thyroid carcinoma (MTC) or patients with multiple endocrine neoplasia syndrome type 2 (MEN 2).
9. Body mass index (BMI) less than 19.
10. Known hypersensitivity to GLP-1 RAs.
11. Active treatment with an GLP-1RA prior to randomization.
12. Refusal or inability to administer subcutaneous (SC) injections by the patient or a caregiver.
13. Close affiliation with the investigational site.

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
No Intervention: No Intervention
Experimental: Semaglutide	Drug: Semaglutide; Glucagon-like peptide-1 (GLP-1) receptor agonist; Other Names: Ozempic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility - Recruitment	Recruitment of approximately 10 patients per site per year at approximately 10 Canadian stroke centres	From site activation until the end of recruitment (approximately 24 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility - Medication Adherence	Target >75% medication adherence	From randomization to day 90±14
Feasibility - Retention Rate	Target >90% of study participants remaining in the trial	From randomization to day 90±14

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Outcome	Recurrent stroke (ischemic, hemorrhagic or uncertain)	Randomization to day 90±14
Exploratory Outcome	Occurrence of MACE (any stroke, myocardial infarction cardiovascular death)	Randomization to day 90±14
Exploratory Outcome	Proportion of participants with functional independence (modified Rankin Scale (mRS) scores 2 or less)	At day 90±14
Exploratory Outcome	Absolute difference in the National Institutes of Health Stroke Scale (NIHSS) scores between randomization and 36±12 hours	Randomization and 36±12 hours
Exploratory Outcome	Functional outcome assessed with the ordinal modified Rankin Scale (mRS) scores	At day 7±2
Exploratory Outcome	Proportion of participants with functional independence (modified Rankin Scale (mRS) scores 2 or less)	At day 7±2
Exploratory Outcome	Functional outcome assessed with the ordinal modified Rankin Scale (mRS) scores	At day 30±7
Exploratory Outcome	Proportion of participants with functional independence (modified Rankin Scale (mRS) scores 2 or less)	At day 30±7
Exploratory Outcome	Functional outcome assessed with the ordinal modified Rankin Scale (mRS) scores	At day 90±14
Exploratory Outcome	Quality of life assessed with the EuroQol 5-Dimension 5-Level (EQ-5D-5L) scale	At day 90±14

Collaborators and Investigators

• Sponsor: Population Health Research Institute
• Investigators: Principal Investigator: Aristeidis Katsanos, MD, Population Health Research Institute; Principal Investigator: Ashkan Shoamanesh, MD, Population Health Research Institute; Principal Investigator: Mike Sharma, MD, Population Health Research Institute

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: March 30, 2026
• First Submitted That Met QC Criteria: March 30, 2026
• First Posted (Actual): April 6, 2026

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: stroke; semaglutide; GLP-1 RA; large vessel occlusion; glucagon-like peptide-1 receptor agonist; endovascular thrombectomy
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Ischemic Stroke; Stroke; semaglutide
• Other Study ID Numbers: LEAST

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

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