GLP-1 Receptor Agonist in Primary Intracerebral Hemorrhage: A Phase 2 Randomized Trial

NCT07613437 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CREC 2026.169
• Study Type: interventional
• Target: 200
• Locations: 2 countries
• Sites: 3

Brief Summary

Intracerebral hemorrhage (ICH) is a devastating form of acute stroke with poor clinical outcomes. Although ICH accounted only for 28.8% of incident strokes, it was responsible for nearly half of the long-term burden of stroke measured in disability-adjusted life years . In contrast to the improving outcomes seen in ischemic stroke with advances in reperfusion therapy, outcomes of patients with ICH have shown little progress over the past two decades. Current standard care focuses primarily on blood pressure control and supportive management, yet rate of functional independence remained modest. Randomized evidence suggested that fewer than half of the ICH patients achieved independent activities of daily living even with intensive blood pressure lowering. A cascade of pathophysiological events is thought to determine the prognosis of ICH. First, the mass effect of the hematoma and its expansion with uncontrolled blood pressure cause primary neuronal injury. Second, neuroinflammation involving blood-brain barrier (BBB) dysfunction, activated microglia and astrocytes, together with neutrophil infiltration in response to extravascular blood, propagates neuronal injury, leading to perihematomal edema. Third, the direct neurotoxicity of blood breakdown products and oxidative stress may further amplify neuroinflammation. Mitigating hematoma expansion through intensive blood pressure control therefore only addresses one of these three pathophysiological processes, and is constrained by a short treatment window, mostly within 6 hours. Therapeutic strategies targeting secondary neuroinflammation should therefore be actively pursued. In addition, multimodal studies incorporating longitudinal imaging and omics markers are needed to elucidate the key pathways mediating neuroinflammation following ICH. Recent preclinical evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RA) may offer neuroprotective benefits in ICH. In animal models of ICH, intracerebroventricular liraglutide suppressed neuroinflammation, prevented brain edema, and reduced neurologic deficits. Previous work from our group has also shown that, across several animal models, GLP-1RA attenuates BBB dysfunction and suppresses neuroinflammatory signaling via microglial modulation. Importantly, a recent translational clinical trial by our team has also provided preliminary evidence that GLP-1RA exerts neuroprotective effects in patients with large vessel occlusion strokes. We therefore hypothesize that compared to standard therapy, administration of GLP-1RA in patients with primary ICH may limit perihaematomal edema, reduce secondary brain injury, and improve neurological outcomes. In this phase 2, randomized, open-label pilot study with blinded endpoint assessment, we aim to determine the safety and signals for efficacy of GLP-1RA in patients with primary ICH.

Conditions

Intracerebral Hemorrhage

Outcome Measures

Primary Outcomes (1)

• Edema extension distance on Day 7

  The perpendicular distance from the hematoma margin to the outermost extent of perihematomal edema on CT imaging.

  Day 7

Secondary Outcomes (9)

• Proportion of patients with excellent functional outcome (mRS 0-1)

  Day 90±14 and Day 180±14

• Proportion of patients with functional independence (mRS 0-2)

  Day 90±14 and Day 180±14

• Proportion of patients with ambulatory independence (mRS 0-3)

  Day 90±14 and Day 180±14

• Ordinal shift of modified Rankin Scale

  Day 90±14 and Day 180±14

• 6. Neurological function of participants assessed by National Institute of Health Stroke Scale

  Day 3, Day 7, Day 14, Day 30, Day 90 and Day 180

Other Outcomes (3)

• Cognitive function by Montreal Cognitive Assessment

  Day 90, Day 180

• Cognitive function by Mini Mental State Examination

  Day 90, Day 180

• Post ICH seizure or epilepsy

  Day 180

Study Arms (2)

Semaglutide Group

ACTIVE COMPARATOR

Patients randomized into the semaglutide group will receive subcutaneous injections of semaglutide on baseline (D0), Day 7 (D7), Day 14 (D14) and Day 21 (D21) after enrollment.

Drug: Semaglutide, 0.5 mg/mL

Standard of care

NO INTERVENTION

Standard medical therapy

Interventions

Semaglutide, 0.5 mg/mL DRUG

0.5mg weekly via subcutaneous injection, a total of 4 injections are given, on Day 0 (D0 day of enrollment, within 24 hours of ICH onset), Day 7 (D7), Day 14 (D14) and Day 21 (D21) after enrollment.

Semaglutide Group

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Primary spontaneous ICH with hematoma location in putamen (10-30mL) or thalamus (5-15mL) on admission CT imaging. Both locations are selected because they are strongly associated with hypertensive arteriopathy-related ICH and there is limited evidence supporting neurosurgical intervention compared with posterior fossa hemorrhages. The thalamic and putaminal volume cutoffs are based on a recent observational study showing that restricting enrolment to 5-15 mL (thalamus) and 10-30 mL (putamen) enriches for patients with substantial but potentially modifiable prognosis while avoiding extremes with ceiling or floor effects. For patients with hematoma involving both putamen and thalamus, a volume cutoff of 5-30mL will be used.
• \. National Institutes of Health Stroke Scale (NIHSS) score ≥ 6 AND ≤ 25 at presentation
• \. Glasgow Coma Scale (GCS) score ≥ 10
• \. Last-known-well (LKW) to presentation time ≤ 24 hours
• \. Pre-stroke modified Rankin Scale (mRS) ≤ 2
• \. Patients deemed not suitable for acute neurosurgical intervention at the time of randomization
• \. Informed consent obtained from patient (if mentally competent) or legal representative, as per national laws, regulations, and applicable ethics committee requirements

You may not qualify if:

• \. Secondary ICH: ICH due to macrovascular abnormalities (e.g., arteriovenous malformation, aneurysm, arterial dissection, cavernous malformation), coagulopathy, anticoagulant use, antiplatelet overdose, or thrombocytopenia.
• \. ICH with planned neurosurgical procedure prior to randomization, including hematoma evacuation, external ventricular drainage and decompressive craniectomy.
• \. Estimated or known body mass index (BMI) \< 18 kg/m².
• \. Pregnancy, lactation, or positive urine or serum beta human chorionic gonadotropin (β-hCG) test. β-hCG testing should be guided by clinical need.
• \. Creatinine clearance \< 30 mL/min (estimated by Cockcroft-Gault equation or measured)
• \. Severe or fatal comorbid illness with life expectancy \< 3 years (e.g., terminal malignancy, advanced organ failure)
• \. Known history of allergy or hypersensitivity to GLP-1RA.
• \. Family or personal history of multiple endocrine neoplasia (MEN), medullary thyroid carcinoma, or pancreatic carcinoma
• \. Active sepsis at time of randomization, defined as a body temperature of ≥ 38.5C, or suspected or documented infection and acute organ dysfunction, operationalized as an increase in SOFA score ≥ 2 points from baseline (baseline assumed 0 if no pre-existing organ dysfunction)
• \. Contraindications to proposed imaging studies (e.g., pacemaker incompatibility with MRI where applicable)

Sponsors & Collaborators

• Chinese University of Hong Kong: lead
• The First Affiliated Hospital of University of Science and Technology China: collaborator
• First Affiliated Hospital of Wenzhou Medical University: collaborator

Study Sites (3)

The First Affiliated Hospital of University of Science and Technology China

Hefei, Anhui, China

Location

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

Location

Chinese University of Hong Kong

Hong Kong, Hong Kong

Location

MeSH Terms

Conditions

Cerebral Hemorrhage

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Bonaventure Yiu Ming IP, MB ChB,PhD

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

• Wei HU, MD

  The First Affiliated Hospital of University of Science and Technology China

  PRINCIPAL INVESTIGATOR

• Xinshi WANG, MD

  First Affiliated Hospital of Wenzhou Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bonaventure Yiu Ming IP, MB ChB,PhD

CONTACT

852-28902002; bonaventureip@cuhk.edu.hk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 200 participants will be randomized in a 1:1 ratio to receive additional semaglutide or just standard therapy after a written informed consent.

Study Record Dates

• First Submitted: May 22, 2026
• First Posted: May 29, 2026
• Study Start: June 15, 2026
• Primary Completion (Estimated): June 14, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: May 29, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1); CN (2)