Stroke, Acute Ischemic Stroke
Conditions
Keywords
GM1, Mechanical Thrombectomy, Acute Anterior Circulation Large Vessel Occlusion
Brief summary
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.
Interventions
DRUGIntravenous 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.
DRUGPlacebo 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.
Sponsors
Xuanwu Hospital, Beijing
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Rate of mRS score of 0-2 | 90 days (±7 days) after randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| mRS scores (ordinal-shift analysis) | 90 days (±7 days) after randomization | 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. |
| NIHSS Score Change | 48hours (±48 hours) after randomization | 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 |
| Rate of early neurological improvement | 48hours (±12 hours) after randomization | the NIHSS score 0-1 or decrease ≥4 from baseline NIHSS |
| EQ-5D score | 90 days (±7 days) after randomization | 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. |
| Barthel Index | 90 days (±7 days) after randomization | — |
Countries
China
Contacts
CONTACTXuesong Bai
Outcome results
None listed