Safety and Efficacy of Adjunctive GM1 to Mechanical Thrombectomy for Acute Anterior Circulation Large Vessel Occlusion (IAT-GIANT)

Safety and Efficacy of Adjunctive GM1 to Mechanical Thrombectomy for Acute Anterior Circulation Large Vessel Occlusion: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study-IAT-GIANT (Ganglioside GM1 to Improve Outcomes in Anterior CirculatioN Thrombectomy)

Stroke is a leading cause of global mortality and morbidity, with acute ischemic stroke (AIS) accounting for approximately 65.3% of cases and resulting in roughly 3.4 million new cases annually in China. While endovascular thrombectomy (EVT) is the recommended first-line therapy for large vessel occlusion (LVO), achieving 80-90% recanalization, fewer than 50% of patients reach functional independence (mRS 0-2) due to "futile recanalization" caused by mechanisms like no-reflow and reperfusion injury. Monosialotetrahexosylganglioside (GM1) is a unique glycosphingolipid that crosses the blood-brain barrier to provide neuroprotection by suppressing oxidative stress, excitotoxicity, and apoptosis while promoting neurogenesis. Although Phase III trials like the FOCUS study confirmed GM1's safety and efficacy in AIS populations, its benefit specifically for patients undergoing mechanical thrombectomy remains unkown. Therefore, the IAT-GIANT study is a multicenter, randomized, double-blind, placebo-controlled trial designed to evaluate the safety and efficacy of adjunctive GM1 in improving 90-day functional outcomes for AIS-LVO patients treated with EVT.

Study Overview

• Status: Recruiting
• Conditions: Stroke; Acute Ischemic Stroke
• Intervention / Treatment: Drug: Placebo Therapy; Drug: Intravenous GM1 Therapy

• Study Type: Interventional
• Enrollment (Estimated): 868
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Xuesong Bai; Phone Number: Xuanwu Hospital; Email: bxsben@163.com

Study Locations

• China
  • Heze
    • Shandong, Heze, China
      • Recruiting
      • Heze Municipal Hospital
      • Contact: Kai Li, MD.; Phone Number: +86-18661581160; Email: 18661581160.bz0508@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1.Age ≥18 years and ≤80 years
• 2.Symptoms and signs consistent with anterior circulation ischemia;
• 3.Computed tomography angiography (CTA) /magnetic resonance angiography (MRA) /digital subtraction angiography (DSA) confirmed occlusion of intracranial segment of internal carotid artery (ICA) or M1/M2 segments of the middle cerebral artery (MCA M1/M2);
• 4.Acute ischemic stroke (AIS) selected for emergency endovascular treatment;
• 5.Premorbid mRS ≤1;
• 6.Time from symptom onset to randomization was within 24 hours, including patients with wake-up stroke or unwitnessed stroke; The time of symptom onset was defined as the Last Known Well (LKW);
• 7.National Institutes of Health Stroke Score (NIHSS) ≥6 at admission;
• 8.ASPECTS ≥3;
• 9.Informed consent obtained from the patient or his/her legal representative.

Exclusion Criteria:

• 1.Simultaneous acute occlusion of large vessels in both the anterior and posterior circulation or bilateral cerebral hemispheres.
• 2.Baseline NIHSS is not obtained by a neurologist or emergency physician prior to sedation or intubation;
• 3.Seizures at stroke onset which would preclude obtaining a baseline NIHSS;
• 4.Bilateral dilated pupils;
• 5.Allergy to GM1 or excipients;
• 6.Severe contrast allergy or absolute contraindication to iodinated contrast;
• 7.Systolic pressure >185 mmHg or diastolic pressure >110 mmHg, and cannot be controlled by antihypertensive drugs;
• 8.Blood glucose <50 mg/dl (2.8 mmol/L) or >400 mg/dl (22.2 mmol/L);
• 9.Platelet <50*10^9/L;
• 10.Known genetic or acquired bleeding diathesis, deficiency of anticoagulant factors, or oral anticoagulant drugs and INR > 1.7, or treated with direct oral anticoagulant agents in the prior 48 hours;
• 11.Known Severe renal Failure as defined by a serum creatinine > 3.0 mg/dl (or 265.2 μmol/l) or glomerular filtration rate (GFR) <30, or patient requires hemodialysis or peritoneal dialysis;
• 12.Patients that cannot complete 90-day follow-up (e.g. no fixed residence, overseas patients, etc.);
• 13.Presumed vasculitis or septic embolization;
• 14.Suspicion of aortic dissection;
• 15.Evidence indicates intracranial tumors (excluding small meningiomas), acute intracranial hemorrhage, tumors, or arteriovenous malformations (AVMs).
• 16. Significant mass effect causing midline shift.
• 17. The patient has neurological disease or mental disorder before onset, which affects the assessment of the condition;
• 18.Females who are pregnant or in lactation;
• 19.Hereditary glycolipid metabolic disorders (ganglioside storage diseases, such as familial amaurotic idiocy, retinal degenerative diseases);
• 20.Autoimmune diseases, spine injuries, demyelinating diseases (e.g., Guillain-Barre syndrome)
• 21.Participating in other clinical trials that could confound the evaluation of the study;
• 22.Other circumstances that the investigator considers inappropriate for participation or may pose a significant risk to patients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Therapy	Drug: Placebo Therapy; The control group will receive a placebo containing excipients only (without GM1). The placebo will be dissolved in normal saline and administered using the same methods, duration, and dosage regimen as the active treatment group. The appearance, preparation, and administration procedures of the placebo will be identical to those of the investigational drug to ensure blinding.
Experimental: Intravenous GM1 Therapy	Drug: Intravenous GM1 Therapy; Patients should receive intravenous administration of GM1 as soon as possible after randomization (Highly recommend within 2 hours.) The GM1 group will receive 200mg daily until day 7 after randomization or hospital discharge by intravenous infusion (Qilu Pharmaceutical Co., Ltd., Jinan, China). GM1 will be dissolved in 100ml normal saline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of mRS score of 0-2	90 days (±7 days) after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of mRS score of 0-1		90 days (±7 days) after randomization
Rate of mRS score of 0-3		90 days (±7 days) after randomization
Rate of early neurological improvement	the NIHSS score 0-1 or decrease ≥4 from baseline NIHSS	48hours (±12 hours) after randomization
Barthel Index		90 days (±7 days) after randomization
mRS scores (ordinal-shift analysis)	The modified Rankin Scale (mRS) is an ordinal scale ranging from 0 to 6 that measures the degree of disability or dependence in daily activities after stroke. Higher scores indicate greater disability. 0 No symptoms at all.; No significant disability despite symptoms; able to carry out all usual duties and activities.; Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance.; Moderate disability; requiring some help, but able to walk without assistance.; Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance.; Severe disability; bedridden, incontinent, and requiring constant nursing care and attention.; Dead.	90 days (±7 days) after randomization
NIHSS Score Change	The National Institutes of Health Stroke Scale (NIHSS) is a standardized neurological examination scale used to quantify stroke-related neurological deficits and assess stroke severity. The NIHSS evaluates level of consciousness, gaze, visual fields, facial palsy, motor arm and leg function, limb ataxia, sensory function, language, dysarthria, and extinction/inattention. The total NIHSS score is calculated by summing the individual item scores and ranges from 0 to 42, with 0 indicating no neurological deficit and higher scores indicating greater stroke severity. 1a Level of Consciousness 0-3 1b Level of Consciousness Questions 0-2; c Level of Consciousness Commands 0-2; Best Gaze 0-2; Visual Fields 0-3; Facial Palsy 0-3; a Motor Arm, Left 0-4 5b Motor Arm, Right 0-4 6a Motor Leg, Left 0-4 6b Motor Leg, Right 0-4 7 Limb Ataxia 0-2 8 Sensory 0-2 9 Best Language 0-3 10 Dysarthria 0-2 11 Extinction and Inattention 0-2	48hours (±48 hours) after randomization
NIHSS Score Change	The National Institutes of Health Stroke Scale (NIHSS) is a standardized neurological examination scale used to quantify stroke-related neurological deficits and assess stroke severity. The NIHSS evaluates level of consciousness, gaze, visual fields, facial palsy, motor arm and leg function, limb ataxia, sensory function, language, dysarthria, and extinction/inattention. The total NIHSS score is calculated by summing the individual item scores and ranges from 0 to 42, with 0 indicating no neurological deficit and higher scores indicating greater stroke severity. 1a Level of Consciousness 0-3 1b Level of Consciousness Questions 0-2; c Level of Consciousness Commands 0-2; Best Gaze 0-2; Visual Fields 0-3; Facial Palsy 0-3; a Motor Arm, Left 0-4 5b Motor Arm, Right 0-4 6a Motor Leg, Left 0-4 6b Motor Leg, Right 0-4 7 Limb Ataxia 0-2 8 Sensory 0-2 9 Best Language 0-3 10 Dysarthria 0-2 11 Extinction and Inattention 0-2	7 days after randomization or discharge
EQ-5D score	The EQ-5D-5L is a standardized measure of health-related quality of life developed by the EuroQol Group. It consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has five response levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Responses across the five dimensions are combined into a 5-digit health state profile. The EQ VAS records the respondent's self-rated health on a vertical visual analogue scale, with endpoints anchored at 100 = the best health the respondent can imagine and 0 = the worst health the respondent can imagine. EQ-5D health states may be converted into a single index value using an appropriate EQ-5D value set, with higher index values indicating better health status.	90 days (±7 days) after randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of any ICH and subtypes	according to the Heidelberg Classification	within 48 hours after randomization
Rate of sICH	according to the Heidelberg Definition	within 48 hours after randomization
Mortality		90 days (±7 days) after randomization

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2026
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): August 31, 2028

Study Registration Dates

• First Submitted: April 1, 2026
• First Submitted That Met QC Criteria: April 1, 2026
• First Posted (Actual): April 9, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Mechanical Thrombectomy; GM1; Acute Anterior Circulation Large Vessel Occlusion
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Ischemic Stroke; Stroke
• Other Study ID Numbers: IAT-GIANT

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No