INdobufen Versus aSpirin in acUte Ischemic stRokE,INSURE

NCT03871517 | Completed Phase 4 DMC

• 1 other identifier: KY 2018-075-02
• Study Type: interventional
• Target: 5,438
• Locations: 1 country
• Sites: 1

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.

Conditions

Ischemic Stroke; Indobufen; Aspirin

Outcome Measures

Primary Outcomes (2)

• Any new stroke event (ischemic stroke or hemorrhagic stroke)

  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.

  3 months after randomization

• Severe or moderate bleeding

  GUSTO definition

  3 months after randomization

Secondary Outcomes (11)

• Any new stroke event

  1 year after randomization

• New vascular events

  1 year after randomization

• New ischemic stroke events

  within 3 months and 1 year after randomization

• modified Rankin Scale (mRS) score was compared between 0-2 and 3-6 in the two groups.

  During the 3-month and 1-year follow-up

• The proportion of mRS scores between 3 to 6 points

  3 months and 1 year

Study Arms (2)

Indobufen

EXPERIMENTAL

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

Drug: Indobufen

Aspirin

ACTIVE COMPARATOR

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

Drug: Aspirin

Interventions

Indobufen DRUG

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

Indobufen

Aspirin DRUG

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

Aspirin

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead

Study Sites (1)

Beijing Tian Tan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100050, China

Location

Related Publications (2)

• 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.

  PMID: 37121237 DERIVED

• 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.

  PMID: 35393360 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Interventions

indobufen; Aspirin

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Executive Vice-President

Study Record Dates

• First Submitted: March 4, 2019
• First Posted: March 12, 2019
• Study Start: June 3, 2019
• Primary Completion: March 1, 2022
• Study Completion: December 1, 2022
• Last Updated: January 9, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)