Methylprednisolone With Endovascular Thrombectomy for Large Ischemic Stroke

Official title

Methylprednisolone With Endovascular Thrombectomy for Large Ischemic Stroke (MATCH): A Randomized Controlled Trial

Overview

It is uncertain whether intravenous methylprednisolone improves outcomes for acute anterior circulation large vascular occlusion (LVO) patients with a large infarct core. In this study, the investigators assume that methylprednisolone plus endovascular thrombectomy (EVT) might be superior to EVT alone for patients who have evidence of a large infarct volume. The objective of the study was to establish the efficacy and safety of methylprednisolone with EVT in patients presenting with symptoms of acute ischemic stroke from LVO in the anterior circulation and having a large infarct volume.

Detailed description

MATCH is a multicentered, prospective, randomized, controlled trial. A total of 1614 patients (age ≥18 years) with NIHSS ≥6 and pre-stroke modified Rankin Scale (mRS) 0-2, within 24 hours of symptom onset of acute ischemic stroke, who has the imaging evidence of an occlusion of the intracranial internal carotid artery (ICA) and/or M1/M2 segment of middle cerebral artery (MCA), large infarct core \[defined as: 1) NCCT (non-contrast computed tomography) ASPECTS (Alberta Stroke Program Early CT Score) 0-5, decided on last head CT scan before randomization. Or 2) Ischemic core volume ≥70ml, determined either on a diffusion-weighted MRI map based on an ADC (Apparent Diffusion Coefficient) threshold of less than 620 or on CTP (computed tomography perfusion) image with rCBF\<30%\] will be enrolled. Patients fulfilling all of the inclusion criteria and none of the exclusion criteria will be randomized 1:1 into two groups after offering informed content. One group will receive methylprednisolone plus EVT, the other group will receive methylprednisolone simulant plus EVT. The primary objective is to evaluate the efficacy of methylprednisolone with EVT in patients presenting with symptoms of acute ischemic stroke from LVO in the anterior circulation and having a large infarct volume. The study consists of four visits including the day of randomization, 36 hours after randomization, 7 days or discharge, and 90 days. The primary outcome is a shift in the distribution of scores on the mRS at 90 days. All the related investigative organization and individuals will obey the Declaration of Helsinki and Chinese Good Clinical Practice standard. A Data and Safety Monitoring Board (DSMB) will regularly monitor safety during the study. The trial has been approved by Institutional Review Board (IRB) and Ethics Committee (EC) in Sun Yat-Sen Memorial Hospital.

Interventions

• Drug Methyprednisolone sodium succinate
  Methylprednisolone at a dose of 2 mg/kg/day for 3 consecutive days, with a maximum daily dose of 160 mg (4 vials, 40 mg per vial, Hanhui Pharmaceutical Co., Ltd.). The initial study drug will be administered as soon as possible after randomization. It is recommended that the initial study drug be administered before arterial access closure.
• Drug Placebo
  Placebo for 3 consecutive days, with a maximum daily dose of 4 vials (Hanhui Pharmaceutical Co., Ltd.)

Primary outcome measures

• 90-day distribution of patients across the ordinal modified Rankin Scale (mRS) [Time frame: 90±14 days after randomization]

Secondary outcome measures (8)

• modified Rankin Scale (mRS) 0-1 at 90±14 days [Time frame: 90±14 days after randomization]
• modified Rankin Scale (mRS) 0-2 at 90±14 days [Time frame: 90±14 days after randomization]
• modified Rankin Scale (mRS) 0-3 at 90±14 days [Time frame: 90±14 days after randomization]
• modified Rankin Scale (mRS) 0-4 at 90±14 days [Time frame: 90±14 days after randomization]
• Quality of Life (EuroQoL 5-Dimension 5-Level) at 90±14 days [Time frame: 90±14 days after randomization]
• National Institutes of Health Stroke Scale (NIHSS) score change from baseline [Time frame: 7±1 days after randomization/discharge]
• Infarct core volume change from baseline [Time frame: 7±1 days after randomization/discharge or at 36±12 hours after randomization]
• Rate of hemicraniectomy within 7 days [Time frame: 7±1 days after randomization/discharge]

Eligibility criteria

Inclusion criteria

• 1\. Age ≥18 years;
• 2\. Clinically diagnosed with acute ischemic stroke and NIHSS ≥6;
• 3\. CT angiography (CTA), MR angiography (MRA) or digital subtraction angiography (DSA) confirmed occlusion of intracranial internal carotid artery (ICA) or M1/M2 segments of middle cerebral artery (MCA) and plan to undergo EVT;
• 4\. ASPECTS ≤5 (based on NCCT) or infarct core volume ≥70mL (defined as rCBF <30% on CT perfusion or ADC <620 on MRI);
• 5\. Time from symptom onset to randomization within 24 hours (from last known well);
• 6\. Pre-stroke mRS score 0-2;
• 7\. Written informed consent signed by patients or their family members.

Exclusion criteria

• 1\. Intracranial hemorrhage confirmed by CT or MRI;
• 2\. Allergic to glucocorticoids or placebo components;
• 3\. Allergic to contrast agent;
• 4\. Presence of severe infectious disease unsuitable for glucocorticoid therapy or any other contraindication to glucocorticoid use;
• 5\. Known genetic or acquired coagulopathy, coagulation factor deficiency, use of warfarin with an international normalized ratio (INR) >1.7, or use of novel oral anticoagulants within 48 hours of symptom onset;
• 6\. Platelet count <90×10\^9/L;
• 7\. Random blood glucose <2.8 mmol/L or >22.2 mmol/L;
• 8\. History of gastrointestinal or urinary tract bleeding within the last month;
• 9\. Current participation in another interventional clinical study;
• 10\. Pregnant or lactating women;
• 11\. Renal dysfunction (glomerular filtration rate <30 ml/min or serum creatinine >220 μmol/L \[2.5 mg/dl\]);
• 12\. Uncontrolled hypertension with persistent systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg, refractory to medical management;
• 13\. Life expectancy less than 6 months due to malignancy or severe cardiopulmonary disease;
• 14\. Other conditions deemed unsuitable for the study by the investigator, such as inability to comprehend or comply with study procedures or follow-up due to mental illness, cognitive or emotional disorder.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Sun Yat-sen Memorial Hospital, Sun Yat-sen University — Guangzhou

Identifiers

NCT: NCT06870448 · SYS-5010-202501

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗