INdobufen Versus aSpirin in acUte Ischemic stRokE,INSURE

Capital Medical University

Status and phase

Completed

Phase 4

Conditions

Indobufen

Ischemic Stroke

Aspirin

Treatments

Drug: Aspirin

Drug: Indobufen

Study type

Interventional

Funder types

Other

Identifiers

NCT03871517

KY 2018-075-02

Details and patient eligibility

About

China has the largest burden of cerebrovascular disease in the world. About 60% to 80% of which are ischemic stroke. In recent years, stroke has replaced heart disease and tumor diseases as the first cause of death and disability in adult population. The primary purpose of this study is to evaluate the efficacy of indobufen treatment in reducing the risk of a 3-month new stroke (any type of stroke, including ischemic stroke and hemorrhagic stroke) for patients with moderate/severe ischemic stroke is not inferior to aspirin therapy.

Full description

Non-inferiority analysis was performed on the primary efficacy analysis, and both intent analysis (ITT) and compliance program set (PPS) were used for analysis. If the indobufen group was confirmed to be non-inferior to aspirin (control group), a superiority analysis was further performed to analyze whether the indobufen was superior to aspirin. At the same time, Kaplan-Meier curves were used to simulate the cumulative risk of stroke (ischemic or hemorrhagic) at 90-day follow-up, and the Cox proportional hazards model was used to calculate the hazard ratio (HR) and 95% confidence interval, Log-rank test was used to evaluate the treatment effect. All statistics will be two-sided with p<0.05 considered significant.

All patients who received study drugs and with at least one safety follow-up record will be included in the safety population. The data for safety evaluation included adverse reactions observed during the trial and changes in laboratory data before and after treatment.

Enrollment

5,438 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Female or male aged≥18 years and<80years.
Acute moderate/severe ischemic stroke, 4≤NIHSS（National Institute of Health stroke scale）≤18 at the time of randomization.
Patients can be randomized within 72 hours of symptoms onset.
Provision of informed consent prior to any study specific procedures. * Symptom onset is defined by the "last seen normal" principle

Exclusion criteria

Diagnosis of intracerebral hemorrhage such as cerebral hemorrhage, subarachnoid hemorrhage, etc.
Diagnosis of hemorrhage or other pathology, such as vascular malformation, tumor, abscess or other major non-ischemic brain disease (e.g., multiple sclerosis) on baseline head CT or MRI.
Moderate to severe ischemic stroke induced by angioplasty/vascular surgery.
Modified Rankin Scale Score>2 at randomization (pre-morbid historical assessment).
History of aneurysm (including intracranial aneurysm or peripheral aneurysms).
Clear indication for anticoagulation (presumed cardiac source of embolus, e.g., atrial fibrillation, atrial myxoma, prosthetic cardiac valves known or suspected endocarditis).
History of Hemostatic disorder, systemic bleeding, thrombocytopenia or neutropenia.
History of previous symptomatic non-traumatic intracerebral bleed or cerebral artery amyloidosis.
Gastrointestinal (GI) bleed within the past 6 months before randomization.
Major surgery within the past 3 months before randomization.
Severe renal or hepatic insufficiency. (Severe hepatic insufficiency is defined as alanine aminotransferase (ALT) value>3 times normal upper limit or Aspartate aminotransferase (AST)>2 times normal upper limit; Severe renal insufficiency is defined as creatinine>2 times normal upper limit).
Diagnosis or of acute coronary syndrome.
Other antithrombotic therapy are required during the study, including antiplatelet therapy(such as open-labeled aspirin, GPIIb/IIIa inhibitors, clopidogrel, ticagrelor, prasugrel, dipyridamole, ozagrel, cilostazol, etc.) and anticoagulant therapy(such as warfarin, thrombin and factor Xa inhibitors, bivalirudin, hirudin, argatroban, heparin and low molecular heparin, etc.).
Within randomized 24 hours prior to any venous or arterial thrombolysis, mechanical bolt, snake venom, defibrase, lumbrokinase, etc.
Heparin or oral anticoagulants were used within 10 days of randomization.
Have a history of drug or food allergy and are known to be allergic to the study drug ingredients
Planned or likely revascularization (any angioplasty or vascular surgery) within the next 3 months (if clinically indicated, vascular imaging should be performed prior to randomization whenever possible)
Anticipated requirement for long-term (>7 days) non-steroidal antiinflammatory drugs (NSAIDs).
The blood pressure needs to be controlled within the range of 90mmHg/60mmHg to 220mmHg/120mmHg.
Suffering from serious cardiopulmonary disease, the researchers believe that it is not suitable for this study
Patients with life expectancy<3 months or patients who are unable to complete the study for other reasons.
Women of childbearing age who are negative in pregnancy test but refuse to practice reliable contraception. Women who are pregnant or lactating.
Involving in other investigational drug or device tests within the past 30 days before randomization.
Inability of the patient to understand and/or comply with study procedures and/or follow-up due to mental illness, cognitive or emotional disorders