Clinical trial NCT05885919: Effect of Early Versus Late Initiation of Edaravone Dexborneol on Neural Function in Patients With Acute Ischemic Stroke
Official title: Effect of Early Versus Late Initiation of Edaravone Dexborneol on Neural Function in Patients With Acute Ischemic Stroke-A Multicenter, Randomized, Double-blind, Placebo-controlled, Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Ischemic Stroke, Acute
Treatment Outcome
Keywords: Acute ischemic stroke
Semi-dark band
Brain cell protection
Time window
Erafurone dextrol injection
Treatment Outcome
Lead sponsor: Xiangya Hospital of Central South University
Sponsor class: OTHER
Collaborators: name: Jiangsu Simcere Pharmaceutical Co., Ltd.
First posted: 2023-06-02
Enrollment: 212
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects with AIS who met the criteria for inclusion were stratified 1:1 from onset to use of the investigational drug: early (\< 3 hours) and late (3-6 hours).

Each layer was then randomly assigned to two groups in a 1:1 ratio: the right group and the placebo group.

Test group:

Edaravone dextronicol concentrated solution for injection, 15ml / time (37.5mg / time, of which edaravone 30mg, (+)-2-camphol 7.5mg), that is, 3 bottles / time, 2 times a day, for 12±2 days;

Control group:

Equal dose of placebo, 15 ml / time, that is, 3 sticks / time, 2 times a day for 12±2 days.
Primary purpose: TREATMENT

Brief summary: The primary objective of this study was to evaluate the efficacy and safety of initiation of edaravone dextivel therapy compared with placebo in patients with acute ischaemic stroke (early and late) and to explore the optimal time window for "brain cell protective therapy" of edaravone dexborneol.

Detailed description: This is a multicentre, randomized, double-blind, placebo-controlled trial that aims to investigate the efficacy and safety of (early and late) initiation treatment of Edaravone Dexborneol versus placebo in patients with acute ischemic stroke, and to explore the optimal time window for "brain cell protective therapy" of Edaravone Dexborneol. Patients who were eligible to the inclusion criteria and ineligible to the exclusion criteria will be stratified by time to trial drug: early (\<3 hours) and late (3-6 hours). Then each layer will be randomly assigned into two groups by a 1:1 ratio after the ICF was received. Patients in one arm will be given 15ml edaravone and dexborneol concentrated solution for injection (37.5mg, containing edaravone 30mg and dexborneol 7.5mg) twice a day for 10-14 days, and those in the other arm will be given an equivalent placebo drug. All patients will be followed up for 90 days. The primary outcome is the proportion of modified Rankin Scale 0-2 and the safety outcome is the proportion of severe adverse events.

Eligibility criteria: Inclusion Criteria:

* Age 18-80 years old, gender is not limited;
* Clinically confirmed acute ischemic stroke;
* Within 6 hours of the onset of this stroke;
* NIHSS score of 4-24 at enrollment;
* mRS score before onset≤ 1 point;
* Subject and subject's agent are able and willing to sign informed consent.

Exclusion Criteria:

* CT indicates intracranial hemorrhagic diseases, such as hemorrhagic stroke, subdural hematoma, ventricular hemorrhage, or subarachnoid hemorrhage, etc.;
* Previously known severe liver or kidney insufficiency (ALT or AST is greater than 3.0×ULN; serum Creatinine (SCr) is greater than 1.5×ULN, Creatinine Clearance (CrCl) is less than 50 ml/min or dialysis;
* Systolic blood pressure≥220 mmHg or \<90mmHg；
* Recent stroke within prior 1 month；
* Hypersensitive to edaravone, (+)-2- dexborneol or auxiliary materials;
* Prior receipt of edaravone or any other neuroprotective drugs;
* History of congenital or acquired hemorrhagic disease, coagulation factor deficiency disease, or thrombocytopenic disease, etc.;
* Pregnancy, lactation, or planned pregnancy within 90 days;
* Those who cannot complete informed consent or follow-up treatment due to severe mental disorder or dementia;
* Those with a malignant tumor, severe systemic diseases, or predict survival time \<90 days;
* Participate in another interventional clinical study within 30 days before randomization or participate in another interventional clinical study;
* The investigators consider the patients are not suitable for this trial.

Primary outcomes:
measure: A 90-day mRS score of 0 to 2 in participants with acute ischaemic stroke
timeFrame: 90 days
Secondary outcomes:
measure: Neurological recovery
timeFrame: 90 days
measure: Modified Rankin scale
timeFrame: 90 days
measure: Quality of life score (EQ-5D)
timeFrame: 90 days
measure: The incidence of serious adverse events
timeFrame: 90 days
measure: All-cause mortality
timeFrame: 90 days
Other outcomes:
Locations:
city: Changsha
country: China
facility: Brain Hospital of Hunan Province
state: Hunan
city: Changsha
country: China
facility: Hunan Provincial People's Hospital
state: Hunan
city: Changsha
country: China
facility: XiangYa School of Medicine
state: Hunan
Study officials:
affiliation: Department of Neurology，XiangYa School of Medicine
name: Zhang Le, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Xu J, Wang A, Meng X, Yalkun G, Xu A, Gao Z, Chen H, Ji Y, Xu J, Geng D, Zhu R, Liu B, Dong A, Mu H, Lu Z, Li S, Zheng H, Chen X, Wang Y, Zhao X, Wang Y; TASTE Trial Investigatorsdagger. Edaravone Dexborneol Versus Edaravone Alone for the Treatment of Acute Ischemic Stroke: A Phase III, Randomized, Double-Blind, Comparative Trial. Stroke. 2021 Mar;52(3):772-780. doi: 10.1161/STROKEAHA.120.031197. Epub 2021 Feb 16.
citation: GBD 2019 Stroke Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol. 2021 Oct;20(10):795-820. doi: 10.1016/S1474-4422(21)00252-0. Epub 2021 Sep 3.