Glucagon-like Peptide 1 Receptor Agonist in Acute Large Vessel Occlusion Stroke After Endovascular Treatment (GALLOP2)

The goal of this clinical trial is to learn if semaglutide works to treat acute ischemic stroke (AIS). It will also learn about the safety of semaglutide in AIS. The main question it aims to answer is: Does semaglutide improve the 90-days functional outcome in participants with acute large vessel occlusion who receive the endovascular treatment (EVT)? Researchers will compare semaglutide injection to non-injection to see if semaglutide works to improve the functional outcome in participants with EVT.

Participants will:

• Receive 0.5mg semaglutide injection before (Day 0) and 1 week (Day 7) after EVT , or EVT alone.
• Have additional blood test before and after EVT.
• Receive neurological assessment before EVT, Day 1, Day 3, Day 5-7 after EVT or on hospital discharge (whichever earlier), Day 90±14 after EVT. Audio or video of the assessment may be recorded if possible.
• Receive brain CT + CT angiogram + CT perfusion and MRI after EVT, where the CT scan may be repetitive.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Ischemic Stroke; Large Vessel Occlusion; Endovascular Treatment; Neuroprotective Drugs
• Intervention / Treatment: Drug: Semaglutide 0.5 mg; Other: Standard medical treatment

• Study Type: Interventional
• Enrollment (Estimated): 390
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Wei Hu, MD, PhD; Phone Number: +86 055162284313; Email: andinghu@ustc.edu.cn

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • The First Affiliated Hospital of University of Science and Technology of China
      • Contact: Wei Hu, MD,PhD; Phone Number: +8615155510611; Email: andinghu@ustc.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. LVO stroke at terminal ICA, M1 or dominant M2 with an LKW-to-randomization ≤24 hours
2. Age ≥ 18 years old
3. National Institute of Health Stroke Scale ≥ 6 at the time of brain imaging
4. Acute LVO stroke due to thromboembolism or intracranial stenosis
5. Patients who received computer tomographic or magnetic resonance angiography
6. ASPECTS ≥ 6 for patients with LKW-to-randomization ≤6 hours
7. Salvageable ischemic penumbra demonstrated by CT perfusion or MRI for patients with LKW-to-randomization between 6 and 24 hours
8. Informed consent obtained from patient or acceptable patient surrogate.

Exclusion Criteria:

1. Use of intravenous thrombolytic therapy (alteplase or tenecteplase)
2. Pre-stroke mRS > 2 for patients <80 years and > 1 for patients ≥ 80 years old
3. Intracranial hemorrhage or brain tumour on initial imaging (except small meningiomas)
4. Simultaneous occlusion of bilateral anterior circulation, or both anterior and posterior circulation
5. Unstable hemodynamics on presentation that require resuscitation
6. Systolic blood pressure >185mmHg or diastolic blood pressure >110mmHg that cannot be controlled by antihypertensive drugs
7. Severe comorbid illness, e.g. terminal malignancy with life expectancy <1 year
8. Pregnant or lactating female
9. Participation in another clinical trial
10. Contraindications to GLP1-RA, including history of allergy to GLP-1RA, family or personal history of multiple endocrine neoplasia, medullary thyroid or pancreatic carcinoma, or proliferative diabetic retinopathy
11. Blood glucose <2.7 or > 22.2 mmol/L; platelet count <50x10^9 /L; INR >1.7
12. Patients with known estimated glomerular filtration rate of <30ml/min/1.73m2 or creatinine >3mg/dL (265.2µmol/L); chronic liver disease with Child's Pugh score C or above; or recurrent unexplained hypoglycemia.
13. Suspected or confirmed vasculitis of the central nervous system
14. Unable to complete 90-day follow-up assessment

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
Experimental: semaglutide; Participants will receive 0.5mg semaglutide injection before (Day 0) and 1 week (Day 7) after EVT. Additionally, they will receive antiplatelet drugs, anticoagulation or combinations of these treatment modality according to national and institutional guidelines.	Drug: Semaglutide 0.5 mg; 0.5mg semaglutide injection before and 1 week after endovascular treatment.; Other: Standard medical treatment; Standard medical management
Placebo Comparator: Standard medical management; Standard medical management. Participants will receive EVT, antiplatelet drugs, anticoagulation or combinations of these treatment modality according to national and institutional guidelines.	Other: Standard medical treatment; Standard medical management

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The ordinal shift of modified Rankin Scale	The Modified Rankin Scale (mRS) measures degree of disability/dependence after a stroke, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death	90±14 days after procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with functional independence outcome (mRS 0-1) at day 90	Modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)	90±14 days after procedure
Proportion of patients with functional independence outcome (mRS 0-2) at day 90	modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)	90±14 days after procedure
Proportion of patients with ambulatory and self-care capable outcome (mRS 0-3) at day 90	Modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)	90±14 days after procedure
Neurological Function of Participants Assessed by National Institute of Health Stroke Scale	Zero indicates no stroke symptoms, 1-4 , 5-15, 16-20, 21-42 indicate minor, moderate, moderate to severe, and severe stroke, respectively.	Day 1, Day 3, Day 5-7 after EVT (or at discharge, when the patient is discharged on day 5-7)
Health-related Quality of Life of Participants Assessed by EuroQol-5 Dimension-5 Level	Participants rated themselves on five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension was distributed from "no problems at all" to "very serious problems".	90±14 days after endovascular treatment
Activities of Daily Living of Participants Assessed by Bathel Index	10 rating items, each of which is categorized into 2-3 out of 5 levels: Unable, Needs major help, Needs help, Needs minor help, and Independent, and each item has a different score for each level. Independence was positively correlated with the final score.	90±14 days after procedure

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracranial Hemorrhage (ICH)	ICH means Heidelberg classification 2 or above intracerebral hemorrhage with increment of NIHSS ≥ 4.	48-72 hours after EVT

Collaborators and Investigators

• Sponsor: Wei Hu
• Collaborators: Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: January 14, 2025
• First Submitted That Met QC Criteria: January 21, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 21, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Ischemic Stroke; Stroke; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; Semaglutide
• Other Study ID Numbers: GALLOP2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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.: No