Safety and Efficacy of Edaravone Dexborneol for Acute Ischemic Stroke

Safety and Efficacy of Edaravone Dexborneol for Acute Ischemic Stroke: A Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial

The purpose of this study is to determine the efficacy and safety of edaravone dexborneol in treating acute ischemic stroke.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Edaravone dexborneol; Drug: Placebo

Detailed Description

In this study, 1200 patients with acute ischemic stroke within 48 hours from the onset are included in several centres in China according to the principles of randomization, double-blind, and parallel control. The experimental group receives basic treatment and edaravone dexborneol injection for 7 consecutive days, and sequentially receives a sublingual dose of edaravone dexborneol for 21 consecutive days. The placebo group receives basic treatment and edaravone dexborneol placebo injection for 7 consecutive days and sequentially receives a sublingual dose of edaravone dexborneol placebo drug for 21 consecutive days. Two groups will be followed up at day 90 to evaluate the efficacy and safety of edaravone dexborneol in treating acute ischemic stroke.

• Study Type: Interventional
• Enrollment (Estimated): 1200
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yi Yang, MD,PhD; Phone Number: 0086 13756661217; Email: doctoryangyi@163.com
• Study Contact Backup: Name: Zhen-Ni Guo, MD,PhD; Phone Number: 0086 18186872986; Email: zhen1ni2@163.com

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China, 130000
      • The First Hospital of Jilin University
      • Contact: Yi Yang, MD,PhD; Phone Number: +86-18186872986; Email: doctoryangyi@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥ 18 years old and ≤ 80 years old, regardless of gender;
2. Patients diagnosed as acute ischemic stroke according to "key points for diagnosis of all kinds of major cerebrovascular diseases in China 2019", and able to randomise and initiate edaravone dexborneol treatment less than or equal to 48 hours of stroke onset.
3. Total National Institute of Health stroke scale (NIHSS)≥6 and ≤24, and the sum of NIHSS score for the upper limb and the lower limb is greater than or equal to 2;
4. modified Rankin Scale (mRS) score of 1 or less before onset.
5. Did not receive edaravone dexborneol treatment before enrollment;
6. The informed consent approved by the ethics committee was voluntarily signed by the patient or his legal representative.

Exclusion Criteria:

1. Reperfusion therapy (intravenous thrombolysis and endovascular therapy) has been received or planned after stroke onset.
2. Transient ischemic attack (TIA);
3. Posterior circulation stroke;
4. Intracranial hemorrhagic diseases seen in head imaging: hemorrhagic stroke, epidural hematoma, intracranial hematoma, intraventricular hemorrhage, subarachnoid hemorrhage, etc;
5. Severe disturbance of consciousness: the item score of 1a consciousness level of NIHSS was more than 1;
6. Patients with severe mental disorders and dementia;
7. Systolic blood pressure after blood pressure control is still higher than 220mmhg or diastolic blood pressure was higher than 120mmhg;
8. Severe cardiac insufficiency, dissection and acute pericarditis; Severe liver insufficiency, ALT or AST > 3.0 × ULN; Or severe active liver diseases have been diagnosed, such as acute hepatitis, chronic active hepatitis, cirrhosis, etc;Severe renal insufficiency, Serum Creatinine (SCr) is greater than 200μmol/L, Creatinine Clearance (CrCl) is less than 30 ml/min or receiving hemodialysis; Or suffering from severe systemic diseases, the estimated survival time is less than 90 days;
9. Complicated with malignant tumor or undergoing anti-tumor treatment;
10. Therapeutic neuroprotective agents have been applied after onset of stroke, including commercially available edaravone, nimodipine, ganglioside, citicoline, piracetam, butyl benzene peptides, Urinary Kallidinogenase, Ginkgolide.
11. Patients during pregnancy, lactation and planned pregnancy;
12. Allergic to dexborneol or edaravone or excipients;
13. Have participated in other clinical studies or are participating in other clinical studies within 30 days before randomization;
14. Patients who are unwilling to be followed up，and 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Edaravone dexborneol group; Edaravone dexborneol injection 37.5mg every 12 hours for 7 days and a sublingual dose of edaravone dexborneol 36 mg twice a day for 21 days.	Drug: Edaravone dexborneol; Edaravone dexborneol injection 37.5mg (edaravone 30mg and dexborneol 7.5mg) and 100ml of 0.9% saline every 12 hours for 7 days; sequentially a sublingual dose of edaravone dexborneol 36 mg (edaravone, 30 mg; dexborneol, 6 mg) twice a day for 21 days.
Placebo Comparator: Placebo group; Placebo injection every 12 hours for 7 days and a sublingual dose of placebo drug twice a day for 21 days.	Drug: Placebo; Placebo injection every 12 hours for 7 days; sequentially a sublingual dose of placebo drug twice a day for 21 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
modified rankin scale (mRS) score ≤ 1	The proportion of patients with mRS score of 1 or less on day 90 after randomization. Ranged from 0 to 6, a low value represents a better outcome.	Day 90 after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum ubiquitin C-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), S100β, neuron-specific enolase (NSE) levels		Day 3 after randomization
Serum ubiquitin C-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), S100β, neuron-specific enolase (NSE) levels		Day 7 after randomization
NIHSS score on day 7	NIHSS (National Institute of Health stroke scale) score on day 7 after randomization. NIHSS ranged from 0 to 42, a low value represents a better outcome.	Day 7 after randomization
mRS score ≤ 2	The proportion of patients with an mRS score of 2 or less on day 90 after randomization. Ranged from 0 to 6, a low value represents a better outcome.	Day 90 after randomization
Distribution of mRS score	Distribution of modified Rankin score on day 90 after randomization. Ranged from 0 to 6, a low value represents a better outcome.	Day 90 after randomization

Collaborators and Investigators

• Sponsor: Yi Yang

Study record dates

Study Major Dates

• Study Start (Estimated): October 30, 2024
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): January 30, 2027

Study Registration Dates

• First Submitted: October 15, 2024
• First Submitted That Met QC Criteria: October 15, 2024
• First Posted (Actual): October 17, 2024

Study Record Updates

• Last Update Posted (Actual): October 17, 2024
• Last Update Submitted That Met QC Criteria: October 15, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Acute Ischemic Stroke; Edaravone Dexborneol
• 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: ED-AIS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No