INdobufen Versus aSpirin in acUte Ischemic stRokE,INSURE

NCT ID: NCT03871517

Last Updated: 2023-01-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 5438 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-03
• Study Completion Date: 2022-12-01

Brief Summary

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.

Detailed Description

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. The study is a multicenter, randomized, double-blind, positive drug parallel control and non-inferiority clinical design.

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.

Conditions

Ischemic Stroke; Indobufen; Aspirin

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Indobufen

Drug: Indobufen and aspirin mimetic Day 1 to 90±7: The first time : Indobufen 100mg + aspirin mimetic The second time: indobufen 100mg

Group Type: EXPERIMENTAL

Indobufen

Intervention Type: DRUG

Indobufen inhibits platelet aggregation by reversibly inhibiting the platelet cyclooxygenase enzyme thereby suppressing thromboxane synthesis.

Aspirin

Drug: Aspirin and Indobufen mimetic Day 1 to 90±7: The first time : aspirin 100mg+ Indobufen mimetic, The second time: indobufen mimetic.

Group Type: ACTIVE_COMPARATOR

Aspirin

Intervention Type: DRUG

Aspirin is a salicylate (sa-LIS-il-ate). It works by reducing substances in the body that cause pain, fever, and inflammation.

Interventions

Indobufen

Indobufen inhibits platelet aggregation by reversibly inhibiting the platelet cyclooxygenase enzyme thereby suppressing thromboxane synthesis.

Intervention Type: DRUG

Aspirin

Aspirin is a salicylate (sa-LIS-il-ate). It works by reducing substances in the body that cause pain, fever, and inflammation.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Tiantan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Yongjun Wang

Executive Vice-President

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Beijing Tian Tan Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Countries

China

References

Pan Y, Meng X, Yuan B, Johnston SC, Li H, Bath PM, Dong Q, Xu A, Jing J, Lin J, Jiang Y, Xie X, Jin A, Suo Y, Yang H, Feng Y, Zhou Y, Liu Q, Li X, Liu B, Zhu H, Zhao J, Huang X, Li H, Xiong Y, Li Z, Wang Y, Zhao X, Liu L, Wang Y; INSURE Investigators. Indobufen versus aspirin in patients with acute ischaemic stroke in China (INSURE): a randomised, double-blind, double-dummy, active control, non-inferiority trial. Lancet Neurol. 2023 Jun;22(6):485-493. doi: 10.1016/S1474-4422(23)00113-8. Epub 2023 Apr 27.

Reference Type: DERIVED

PMID: 37121237 (View on PubMed)

Pan Y, Meng X, Chen W, Jing J, Lin J, Jiang Y, Johnston SC, Bath PM, Dong Q, Xu AD, Li H, Wang Y. Indobufen versus aspirin in acute ischaemic stroke (INSURE): rationale and design of a multicentre randomised trial. Stroke Vasc Neurol. 2022 Oct;7(5):457-461. doi: 10.1136/svn-2021-001480. Epub 2022 Apr 7.

Reference Type: DERIVED

PMID: 35393360 (View on PubMed)

Other Identifiers

KY 2018-075-02

Identifier Type: -

Identifier Source: org_study_id