Methylprednisolone Adjunctive to Endovascular Thrombectomy for Stroke (MIRACLE)

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Patients With Acute Ischemic Strokes With Large Infarct: a Multicenter, Randomized, Double-blind, Placebo-controlled Trial (MIRACLE)

The efficacy and safety of methylprednisolone in acute ischemic stroke patients with large infarct cores (ASPECTS score < 6 or infarct volume ≥50 mL) due to anterior circulation large vessel occlusion have not been clearly established. This is a multi-center, randomized, double-blind, placebo-controlled trial to investigate early combination therapy with methylprednisolone for reperfusion in acute large core infarction.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Ischemic Stroke; Large Infarct Core
• Intervention / Treatment: Drug: Methylprednisolone sodium succinate; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 928
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230001
      • The First Affiliated hospital of USTC
    • Hefei, Anhui, China, 230061
      • Hefei First People's Hospital
    • Taihe Chengguanzhen, Anhui, China, 236600
      • Taihe County People's Hospital
    • Wuhu, Anhui, China, 241001
      • Yijishan Hospital of Wannan Medical College
  • Fujian
    • Anxi, Fujian, China, 362400
      • Anxi County Hospital
    • Anxi, Fujian, China, 362400
      • Anxi Hospital of Traditional Chinese Medicine
    • Fuqing, Fujian, China, 350300
      • Fuqing City Hospital of Fujian
    • Fuzhou, Fujian, China, 350001
      • Union Hospital Affiliated to Fujian Medical University
    • Fuzhou, Fujian, China, 350001
      • Fuzhou University Affiliated Provincial Hospital
    • Fuzhou, Fujian, China, 350003
      • The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine
    • Fuzhou, Fujian, China, 350005
      • Department of Neurology, First Affiliated Hospital Fujian Medical University
    • Fuzhou, Fujian, China, 350025
      • 900th Hospital of PLA Joint Logistic Support Force
    • Longyan, Fujian, China, 364000
      • Longyan First Affiliated Hospital of Fujian Medical University
    • Nanping, Fujian, China, 353000
      • Nanping First Hospital
    • Ningde, Fujian, China, 352100
      • Ningde Municipal Hospital, Ningde Normal University
    • Ningde, Fujian, China, 352100
      • Mindong Hospital
    • Putian, Fujian, China, 351100
      • The First Hospital of Putian City
    • Putian, Fujian, China, 351100
      • Putian University Affiliated Hospital
    • Quanzhou, Fujian, China, 362000
      • The Second Affiliated Hospital of Fujian Medical University
    • Quanzhou, Fujian, China, 362000
      • Quanzhou First Hospital Affiliated to Fujian Medical University
    • Quanzhou, Fujian, China, 362000
      • The 910th Hospital of the Joint Logistics Support Force of the Chinese PLA
    • Sanming, Fujian, China, 365000
      • Sanming First Hospital
    • Shaowu, Fujian, China, 354000
      • Shaowu Municiple Hospital
    • Xiamen, Fujian, China, 361003
      • The First Affiliated hospital of Xiamen University
    • Xiamen, Fujian, China, 361004
      • Zhongshan Hosipital Xiamen University
    • Zhangzhou, Fujian, China, 363000
      • Zhangzhou Municipal Hospital of Fujian Province
    • Zhangzhou, Fujian, China, 363000
      • 909th Hospital of PLA Joint Logistic Support Force
  • Gansu
    • Lanzhou, Gansu, China, 730050
      • Gansu Province Central Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
    • Maoming, Guangdong, China, 525000
      • Maoming People's Hospital
    • Maoming, Guangdong, China, 525000
      • Maoming Hospital of Traditional Chinese Medicine
    • Shantou, Guangdong, China, 515031
      • Shantou Central Hospital
    • Zhanjiang, Guangdong, China, 524001
      • Affiliated Hospital of Guangdong Medical University
    • Zhanjiang, Guangdong, China, 524037
      • Central people' s hospital of zhanjiang
  • Guangxi
    • Yulin, Guangxi, China, 537000
      • Red Cross Hospital of Yulin City
  • Guangzhou
    • Guangzhou, Guangzhou, China, 510180
      • Guangzhou First People's Hospital
  • Guizhou
    • Qingzhen, Guizhou, China, 551400
      • The First People's Hospital of Qingzhen
  • Hainan
    • Haikou, Hainan, China, 570102
      • The First Affiliated Hospital of Hainan Medical University
    • Haikou, Hainan, China, 570311
      • The Second Affiliated Hospital of Hainan Medical University
  • Henan
    • Bishui, Henan, China, 463700
      • Biyan People's Hospital
    • Wacheng Neighborhood, Henan, China, 466600
      • Xihua People's Hospital
    • Zhoukou, Henan, China, 466000
      • Zhoukou Centeral Hospital
    • Zhumadian, Henan, China, 463000
      • ZhuMaDian Centeral Hospital
    • Zhumadian, Henan, China, 463000
      • Zhumadian First People's Hospital
  • Hubei
    • Enshi, Hubei, China, 445000
      • The Central Hospital of Enshi Tujia And Miao Automomous Prefecture
    • Ezhou, Hubei, China, 436000
      • Ezhou Central Hospital
    • Huanggang, Hubei, China, 435300
      • Qichun People's Hospital
    • Huanggang, Hubei, China, 438000
      • Huanggang Central Hospital
    • Huangshi, Hubei, China, 435000
      • Huangshi Central Hospital
    • Jingzhou, Hubei, China, 434000
      • Yangtze University Affiliated Hospital
    • Jingzhou, Hubei, China, 434020
      • Jingzhou Hospital Affiliated to Yangtze University
    • Lichuan, Hubei, China, 445400
      • Lichuan City Ethnic Traditional Chinese Medical Hospital
    • Shiyan, Hubei, China, 442000
      • Shiyan Renmin Hospital
    • Shiyan, Hubei, China, 442000
      • Shiyan Hospital of Integrated Traditional and Western Medicine
    • Shiyan, Hubei, China, 442000
      • Taihe Hospital Affiliated to Hubei University of Medicine
    • Tianmen, Hubei, China, 431700
      • The First People's Hospital of Tianmen in Hubei Province
    • Wuhan, Hubei, China, 430071
      • Zhongnan Hospital of Wuhan University
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
    • Wuhan, Hubei, China, 430022
      • Wuhan No.1 Hospital
    • Wuhan, Hubei, China, 430012
      • Wuhan Hankou Hospital
    • Wuhan, Hubei, China, 430014
      • The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology
    • Wuhan, Hubei, China, 430033
      • The Third People's Hospital of Hubei Province
    • Wuhan, Hubei, China, 430060
      • Wuhan University Renmin Hospital
    • Wuhan, Hubei, China, 430200
      • The First people's Hospital of Jiangxia District
    • Xiangyang, Hubei, China, 441000
      • Xiangyang Hospital of Traditional Chinese Medicine
    • Xiangyang, Hubei, China, 441000
      • Xiangyang No.1 People's Hospital, Hubei University of Medicine.
    • Xianning, Hubei, China, 437100
      • Xianning Central Hospital
    • Yichang, Hubei, China, 443000
      • The Second People's Hospital of Yichang
  • Inner Mongolia
    • Baotou, Inner Mongolia, China, 14040
      • Baotou Central Hospital
  • Jiangsu
    • Xuzhou, Jiangsu, China, 221002
      • The Affiliated Hospital of Xuzhou Medical University
  • Jiangxi
    • Ganzhou, Jiangxi, China, 341000
      • First Affiliated Hospital of Gannan Medical University
    • Ganzhou, Jiangxi, China, 341000
      • Ganzhou People's Hospital, Ganzhou (G.Z.)
    • Jingdezhen, Jiangxi, China, 333000
      • Jingdezhen First People's Hospital
    • Jiujiang, Jiangxi, China, 332000
      • Jiujiang University Affiliated Hospital
    • Jiujiang, Jiangxi, China, 332000
      • The First People's Hospital of Jiujiang
    • Nanchang, Jiangxi, China, 330006
      • Jiangxi Provincial People's Hospital
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital, Jiangxi Medical College, Nanchang University
    • Yingtan, Jiangxi, China, 335000
      • Yingtan People's Hospital
  • Shaanxi
    • Xianyang, Shaanxi, China, 712000
      • The First People's Hospital of Xianyang
  • Shandong
    • Jinan, Shandong, China, 250011
      • Affiliated Hospital of Shandong University of Traditional Chinese Medicine
    • Jinan, Shandong, China, 250013
      • Jinan Central Hospital Affiliated to Shandong First Medical University
    • Liaocheng, Shandong, China, 252000
      • Liaocheng People's Hospital
    • Liaocheng, Shandong, China, 252000
      • Liaocheng Third People's Hospital
    • Qingdao, Shandong, China, 266003
      • The Affiliated Hospital of Qingdao Univercity
    • Tai’an, Shandong, China, 271000
      • The Second Affiliated Hospital of Shandong First Medical University
    • Zoucheng, Shandong, China, 273500
      • Zoucheng People's Hospital, Shandong Province
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200025
      • Ruijin Hospital, Shanghai Jiaotong University School of Medicine
  • Shanxi
    • Taiyuan, Shanxi, China, 30012
      • Shanxi Provincial People's Hospital
    • Taiyuan, Shanxi, China, 30001
      • Cardiovascular Hospital Affiliated to Shanxi Medical University
  • Sichuan
    • Chengdu, Sichuan, China, 611230
      • Chongzhou People's Hospital
    • Gulin, Sichuan, China, 646500
      • Gulin County People's Hospital
    • Mianyang, Sichuan, China, 621000
      • Mianyang 404 Hospital
    • Mianyang, Sichuan, China, 621000
      • Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China
    • Nanchong, Sichuan, China, 637000
      • Affiliated Hospital of North Sichuan Medical College
    • Suining, Sichuan, China, 629000
      • Suining Central Hospital
    • Zigong, Sichuan, China, 643020
      • Zigong Third People's Hospital
  • Tian
    • Tianjin, Tian, China, 300350
      • Tianjin Huanhu Hospital
  • Xinjiang
    • Bole, Xinjiang, China, 833400
      • Bozhou People's Hospital
  • Yunnan
    • Qujing, Yunnan, China, 655000
      • Qujing NO.1 Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 years.
• The time from onset to randomization was within 12 hours.
• Anterior circulation ischemic stroke was preliminarily determined according to clinical symptoms or imaging examination.
• Occlusion of the intracranial internal carotid artery, the M1- or M2-segment of the middle cerebral artery by confirmed by CT angiography (CTA), MR angiography (MRA), or digital subtraction angiography (DSA).
• Baseline National Institutes of Health Stroke Scale (NIHSS) ≥ 6.
• Baseline Alberta Stroke Program Early CT Score (ASPECTS) < 6 (based on non-contrast CT or MRI) and/or core infarct volume ≥ 50 ml (based on CTP with rCBF < 30%).
• Planned treatment with endovascular thrombectomy (EVT).
• Informed consent obtained from patients or their legal representatives.

Exclusion Criteria:

• Intracranial hemorrhage confirmed by cranial CT or MRI.
• mRS score > 2 before onset.
• Pregnant or lactating women.
• Allergic to contrast agents or glucocorticoids.
• Participating in other clinical trials.
• The artery is tortuous so that the thrombectomy device cannot reach the target vessel.
• Bleeding history (gastrointestinal and urinary tract bleeding) in recent 1 month.
• Chronic hemodialysis and severe renal insufficiency (glomerular filtration rate < 30 ml/min or serum creatinine > 220 umol/L [2.5 mg/ dL]).
• Life expectancy due to any advanced disease < 6 months.
• Follow-up is not expected to be completed.
• Intracranial aneurysm and arteriovenous malformation.
• Brain tumors with imaging mass effect.
• Systemic infectious disease.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Methylprednisolone sodium succinate group	Drug: Methylprednisolone sodium succinate; Intravenous injection of methylprednisolone sodium succinate (Chongqing Lai Mei Pharmaceutical Co., Ltd., 40mg/bottle) with a dose of 2mg/kg (maximum dose of 160mg), once daily, for three consecutive days. The initial study drug will be administered as soon as possible after randomisation. It is recommended that the initial study drug administrated before arterial access closure, but it should not be delayed more than 2 hours after arterial access closure.
Placebo Comparator: Placebo group; Methylprednisolone sodium succinate simulant	Drug: Placebo; Intravenous injection of placebo (Chongqing Lummy Pharmaceutical Co., Ltd., 40mg/bottle) with a dose of 2mg/kg (maximum dose of 160mg), once daily, for three consecutive days. The initial study drug will be administered as soon as possible after randomization. It is recommended that the initial study drug administrated before arterial access closure, but it should not be delayed more than 2 hours after arterial access closure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality at 90 (±14) days	Primary Efficacy Outcome. Defined as the number of any cause deaths observed divided by the number of subjects observed over the 90-day study period.	From randomization to 90 (±14) days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of any complications	Secondary Safety Outcome	From date of randomization until the date of discharge, an average of 1 week
Time from randomization to the occurrence of death from any cause at 90 (±14) days	Secondary Efficacy Outcome; To evaluate death rate of the two treatment groups	From randomization to 90 (±14) days
Proportion of patients with mRS score 0 to 4 at 90 (±14) days	Secondary Efficacy Outcome	From randomization to 90 (±14) days
Proportion of patients with mRS score 0 to 3 at 90 (±14) days	Secondary Efficacy Outcome	From randomization to 90 (±14) days
Proportion of patients with decompressive craniectomy after EVT	Secondary Efficacy Outcome	From randomization until the date of discharge, an average of 1 week
NIHSS score at 5-7 days or at early discharge	Secondary Efficacy Outcome	From randomization to 5-7 days ( or at early discharge)
EQ-5D-5L VAS at 90 (±14) days	Secondary Efficacy Outcome	From randomization to 90 (±14) days
Proportion of patients with symptomatic intracranial haemorrhage (SICH) within 48 hours after EVT	Primary Safety Outcome. Based on the modified Heidelberg Bleeding Classification.	From randomization to 48 hours
Proportion of patients with any intracranial haemorrhage (ICH) within 48 hours after EVT	Secondary Safety Outcome. Based on the modified Heidelberg Bleeding Classification.	From randomization to 48 hours
Proportion of patients with pneumonia	Secondary Safety Outcome	From randomization until the date of discharge, an average of 1 week
Proportion of patients with gastrointestinal haemorrhage within 7 days after EVT	Secondary Safety Outcome	From randomization to 7 days
Incidence of any (serious) adverse events	Secondary Safety Outcome	From randomization to 90 (±14) days
Midline shift at 48 hours	Secondary Efficacy Outcome	From randomization to 48 hours
Net water uptake at 48 hours	Secondary Efficacy Outcome	From randomization to 48 hours
mRS ordinal shift at 90 (±14) days (scores 5 and 6 are merged)	Secondary Efficacy Outcome	From randomization to 90 (±14) days
Proportion of patients with mRS score 0 to 2 at 90 (±14) days	Secondary Efficacy Outcome	From randomization to 90 (±14) days
Proportion of patients with mRS score 0 to 1 at 90 (±14) days or return to pre-stroke mRS score (for patients with pre-stroke mRS > 1)	Secondary Efficacy Outcome	From randomization to 90 (±14) days
Proportion of patients with midline shift >5 mm within 48 hours after EVT	Secondary Efficacy Outcome	From randomization to 48 hours
Relative hemispheric volume at 48 hours	Secondary Efficacy Outcome.	From randomization to 48 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
EQ-5D-5L VAS at 1 year	Tertiary Efficacy Outcome	From randomization to 1 year
EQ-5D-5L VAS at 5 years	Tertiary Efficacy Outcome	From randomization to 5 years
mRS ordinal shift at 1 year (scores 5 and 6 are merged)	Tertiary Efficacy Outcome	From randomization to 1 year
Proportion of patients with mRS score 0 to 2 at 1 year	Tertiary Efficacy Outcome	From randomization to 1 year
Proportion of patients with mRS score 0 to 1 at 1 year or return to pre-stroke mRS score (for patients with pre-stroke mRS > 1)	Tertiary Efficacy Outcome	From randomization to 1 year
mRS ordinal shift at 5 years (scores 5 and 6 are merged)	Tertiary Efficacy Outcome	From randomization to 5 years
Proportion of patients with mRS score 0 to 2 at 5 years	Tertiary Efficacy Outcome	From randomization to 5 years
Proportion of patients with mRS score 0 to 1 at 5 years or return to pre-stroke mRS score (for patients with pre-stroke mRS > 1)	Tertiary Efficacy Outcome	From randomization to 5 years

Collaborators and Investigators

• Sponsor: Wan-Jin Chen

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2024
• Primary Completion (Actual): September 30, 2025
• Study Completion (Estimated): June 30, 2030

Study Registration Dates

• First Submitted: April 7, 2024
• First Submitted That Met QC Criteria: April 7, 2024
• First Posted (Actual): April 11, 2024

Study Record Updates

• Last Update Posted (Estimated): December 3, 2025
• Last Update Submitted That Met QC Criteria: November 25, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienetriols; Methylprednisolone; Prednisolone; Methylprednisolone Hemisuccinate
• Other Study ID Numbers: MRCTA,ECFAH of FMU[2024]368-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No