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

Официальное название

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)

Обзор

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.

Вмешательства

• Препарат 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.
• Препарат 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.

Первичные конечные точки

• Rate of mRS score of 0-2 [Срок оценки: 90 days (±7 days) after randomization]

Вторичные конечные точки (8)

• Rate of mRS score of 0-1 [Срок оценки: 90 days (±7 days) after randomization]
• Rate of mRS score of 0-3 [Срок оценки: 90 days (±7 days) after randomization]
• mRS scores (ordinal-shift analysis) [Срок оценки: 90 days (±7 days) after randomization]
• NIHSS Score Change [Срок оценки: 48hours (±48 hours) after randomization]
• Rate of early neurological improvement [Срок оценки: 48hours (±12 hours) after randomization]
• NIHSS Score Change [Срок оценки: 7 days after randomization or discharge]
• EQ-5D score [Срок оценки: 90 days (±7 days) after randomization]
• Barthel Index [Срок оценки: 90 days (±7 days) after randomization]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

• Xuanwu Hospital, Capital Medical University. — Пекин
• Heze Municipal Hospital — Shandong

Идентификаторы

NCT: NCT07519044 · IAT-GIANT

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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