Safety and Efficacy of Adjunctive GM1 to Mechanical Thrombectomy for Acute Anterior Circulation Large Vessel Occlusion

Phase 4RecruitingNCT07519044

Xuanwu Hospital, Beijing868 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

868

Conditions

Stroke Acute Ischemic Stroke

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Rate of mRS score of 0-2

Time frame: 90 days (±7 days) after randomization

Secondary Outcomes

Rate of mRS score of 0-1

Time frame: 90 days (±7 days) after randomization

Rate of mRS score of 0-3

Time frame: 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. 1. No significant disability despite symptoms; able to carry out all usual duties and activities. 2. Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance. 3. Moderate disability; requiring some help, but able to walk without assistance. 4. Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance. 5. Severe disability; bedridden, incontinent, and requiring constant nursing care and attention. 6. Dead.

Time frame: 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 1. c Level of Consciousness Commands 0-2 2. Best Gaze 0-2 3. Visual Fields 0-3 4. Facial Palsy 0-3 5. 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

Time frame: 48hours (±48 hours) after randomization

Rate of early neurological improvement

the NIHSS score 0-1 or decrease ≥4 from baseline NIHSS

Time frame: 48hours (±12 hours) after randomization

NIHSS Score Change

Time frame: 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.

Time frame: 90 days (±7 days) after randomization

Barthel Index

Time frame: 90 days (±7 days) after randomization

Safety and Efficacy of Adjunctive GM1 to Mechanical Thrombectomy for Acute Anterior Circulation Large Vessel Occlusion

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts