Compound Edaravone Injection for Acute Ischemic Stroke

Compound Edaravone Injection for Acute Ischemic Stroke, a Multi-center, Randomized, Double-blind, Multi-dose, Parallel, and Controlled Phase II Trial

1. To investigate the efficacy and safety of multi-doses Compound Edaravone Injection versus Edaravone Injection for acute ischemic stroke patients;
2. To provide evidence for the design of Compound Edaravone Injection Phase III trial.

Study Overview

• Status: Completed
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Compound Edaravone Injection; Drug: Edaravone Injection

• Study Type: Interventional
• Enrollment (Actual): 400
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100191
      • Peking University Third Hospital
    • Beijing, Beijing, China, 100048
      • Navy General Hospital of The Chinese PLA
    • Beijing, Beijing, China, 100050
      • Beijing Tiantan Hospital Affiliated to Capital Medical University
  • Chongqing
    • Chongqing, Chongqing, China, 400010
      • The First Affiliated Hospital of Chongqing Medical University
    • Chongqing, Chongqing, China, 400038
      • The First Affiliated Hospital of Third Military Medical University of Chinese PLA
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital of Sun Yat-sen University
    • Shenzhen, Guangdong, China, 518036
      • Peking University Shenzhen Hospital
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • The Second Hospital of Hebei Medical University
    • Shijiazhuang, Hebei, China, 050051
      • Hebei General Hospital
  • Heilongjiang
    • Haerbin, Heilongjiang, China, 150001
      • The Second Affiliated Hospital of Haerbin Medical University
  • Hunan
    • Changsha, Hunan, China, 410005
      • Hunan Provincial People's Hospital
  • Inner Mongolia
    • Baotou, Inner Mongolia, China, 014040
      • Central Hospital of Baotou
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Nanjing Brain Hospital
    • Nanjing, Jiangsu, China, 210006
      • Nanjing First Hospital
    • Nanjing, Jiangsu, China, 210011
      • The Second Affiliated Hospital of Nanjing Medical University
    • Xuzhou, Jiangsu, China, 221006
      • The Affiliated Hospital of Xuzhou Medical College
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Jiangxi Provincial People's Hospital
  • Liaoning
    • Shenyang, Liaoning, China, 110016
      • The General Hospital of Shenyang Military, Chinese PLA
  • Shandong
    • Jinan, Shandong, China, 250012
      • Qilu Hospital of Shandong University
    • Jinan, Shandong, China, 250033
      • The Second Hospital of Shandong University
    • Qingdao, Shandong, China, 266011
      • QingDao Municipal Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200003
      • Shanghai Changzheng Hospital
    • Shanghai, Shanghai, China, 200025
      • Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
  • Shanxi
    • Taiyuan, Shanxi, China, 030001
      • The Second Affiliated Hospital of Shanxi Medical University
    • Taiyuan, Shanxi, China, 030001
      • The First Affiliated Hospital of Shanxi Medical University
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Tianjin Medical University General Hospital
    • Tianjin, Tianjin, China, 300060
      • Tianjin Huanhu Hospital
    • Tianjin, Tianjin, China, 300000
      • Tianjin People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 33 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Hospitalized patients, diagnosed of ischemic stroke;
• Onset of stroke is less than or equal to 48 hours;
• There are clear signs of neurological deficit: 4≤NIHSS score≤24, and also, the sum of NIHSS score for the upper limb and the lower limb is greater than or equal to 2;
• Patients signed written inform consent.

Exclusion Criteria:

• Cranial CT scan finds intracranial bleeding disorders: hemorrhagic stroke, epidural hematoma, intracranial hematoma, intraventricular hemorrhage, subarachnoid hemorrhage;
• Iatrogenic stroke;
• Severe disturbance of consciousness: NIHSS category 1a for consciousness is greater than 1；
• The mRS score prior to this onset is greater than 1;
• Transient ischemic attack (TIA);
• SBP after blood pressure control is still greater than to equal to 220 mmHg, or DBP after blood pressure control is still greater than or equal to 120 mmHg;
• Patients with severe mental disorders and dementia;
• ALT or AST is greater than 2.0×ULN or previously known liver diseases, such as acute hepatitis, chronic active hepatitis, liver cirrhosis;
• Creatinine clearance is less than 30 ml/min or previously known severe renal diseases;
• Therapeutic neuroprotective agents have been applied after onset, including commercially available edaravone, nimodipine, ganglioside, citicoline, piracetam, butyl benzene peptides, Urinary Kallidinogenase;
• Arterial or venous thrombolytic therapy has been applied after onset;
• With malignant tumors or receiving concurrent antitumor treatment;
• With severe systemic disease, life expectancy is less than 90 days;
• Pregnant or lactating women;
• Participate in other clinical studies within 30 days before randomization;
• The investigators consider the patients are not suitable for this trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-dose group; Compound Edaravone Injection, 12.5mg/dose (Edaravone 10mg, (+)-Borneol 2.5mg), one dose every 12 hours, continue for 14 days	Drug: Compound Edaravone Injection
Experimental: Medium-dose group; Compound Edaravone Injection, 37.5mg/dose (Edaravone 30mg, (+)-Borneol 7.5mg), one dose every 12 hours, continue for 14 days	Drug: Compound Edaravone Injection
Experimental: High-dose group; Compound Edaravone Injection, 62.5mg/dose (Edaravone 50mg, (+)-Borneol 12.5mg), one dose every 12 hours, continue for 14 days	Drug: Compound Edaravone Injection
Active Comparator: Control group; Edaravone Injection，30 mg/dose, one dose every 12 hours, continues for 14 days	Drug: Edaravone Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
mRS score on day 90	day 90
Change from baseline NIHSS score on day 14	day 14

Secondary Outcome Measures

Outcome Measure	Time Frame
The proportion of patients with NIHSS score 0-1 (including motor function) on day 14, 30, 90	day 14, 30, 90
The proportion of patients with Barthel Index (BI) score greater than or equal to 95 on day 14, 30, 90	day 14, 30, 90
The Montreal Cognitive Assessment(MoCA) score on day 14, 30, 90	day 14, 30, 90
Stroke Impact Scale (SIS) score on day 90	day 90

Collaborators and Investigators

• Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Yongjun Wang, MD, Beijing Tiantan Hospital

Publications and helpful links

General Publications

• Xu J, Wang Y, Wang A, Gao Z, Gao X, Chen H, Zhou J, Zhao X, Wang Y. Safety and efficacy of Edaravone Dexborneol versus edaravone for patients with acute ischaemic stroke: a phase II, multicentre, randomised, double-blind, multiple-dose, active-controlled clinical trial. Stroke Vasc Neurol. 2019 Apr 22;4(3):109-114. doi: 10.1136/svn-2018-000221. eCollection 2019 Sep.

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: August 22, 2013
• First Submitted That Met QC Criteria: August 22, 2013
• First Posted (Estimate): August 27, 2013

Study Record Updates

• Last Update Posted (Estimate): July 3, 2015
• Last Update Submitted That Met QC Criteria: July 1, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neuroprotective Agents; Protective Agents; Antioxidants; Free Radical Scavengers; Edaravone
• Other Study ID Numbers: SIM-23-01