Argatroban Combined With Antiplatelet Versus Antiplatelet for Acute Ischemic Stroke

Argatroban Combined With Antiplatelet Versus Antiplatelet for Acute Mild or Moderate Ischemic Stroke With Large-artery Atherosclerosis: a Prospective, Single Center Study

Intravenous thrombolysis is considered as the first choice for ischemic stroke. In the recent years, endovascular therapy is demonstrated to be effective to treat ischemic with big vessel occlusion. However, only a minority of patients can get intravenous thrombolysis or endovascular therapy due to the restricted time window and strict indications. Dual antiplatelet has been demonstrated to be effective in the patients with high risk of TIA or minor ischemic stroke (NIHSS<4). But there is still stroke progression although dual antiplatelet. The ischemic stroke patients with NIHSS > 3 has been recommended to give aspirin in most guidelines. Of those patients, mild to moderate stroke patients (3<NIHSS<10) will result in the poor outcomes if the progression occurs. In addition, large artery atherosclerosis (LAA) stroke is prone to progress. So, we argue that the mild to moderate stroke with LAA should be give more intensive antiplatelet. In the present study, argatroban combined with antiplatelet therapy (3-5 days) is used to treat the proposed patients to investigate the safety and effectiveness.

Study Overview

• Status: Completed
• Conditions: Stroke, Ischemic
• Intervention / Treatment: Drug: Argatroban plus dual antiplatelet

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Liaoning
    • Shenyang, Liaoning, China, 10016
      • General Hospital of Shenyang Military Region

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18-80 years old;
2. Clear diagnosis of ischemic stroke patients with head CT or MRI examination;
3. The time of onset is less than 72 hours;
4. NIHSS score is less than 12 points;
5. the large artery atherosclerosis etiology
6. Signed informed consent.

Exclusion Criteria:

1. Hemorrhagic stroke or mixed stroke;
2. Patients with planned thrombolytic therapy;
3. Serious diseases such as severe infection or liver, kidney, hematopoietic system, endocrine system, etc.;
4. The history of stroke and had serious sequelae (mRS> 1);
5. Allergic to aspirin/clopidogrel and argatroban;
6. ischemic stroke caused by other causes, such as small vessel lesions, cardiogenic embolism, arterial dissection, vasculitis and other cerebral infarction;
7. Previous history of cerebral hemorrhage;
8. It is expected to use other anti-platelet agents or non-steroidal anti-inflammatory agents that affect platelet function;
9. within 3 months of gastrointestinal bleeding or major surgery;
10. any unqualified patients judged by researchers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Argatroban combined with antiplatelet	Drug: Argatroban plus dual antiplatelet; A continuous argatroban infusion of 1.0 ug/kg per minute for 2-5 days adjusted to a target activated partial thromboplastin time of 1.75 X baseline (about 10%). For the first day, clopidogrel with loading dose 300mg, and aspirin 100mg were given, and followed by clopidogrel 75 mg and aspirin 100mg each day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of 1 or more increase in NIHSS	early neurological deterioration is defined as 1 or more increase in NIHSS	7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of mRS 0-1	the excellent outcome is defined as modifed Rankin Score (mRS) 0-1 at 90 day	90±7 days
Proportion of mRS 0-2	the good outcome is defined as modifed Rankin Score (mRS) 0-2 at 90 day	90±7 days
proportion of intracranial haemorrhages	intracranial hemorrhage was defined as acute extravasation of blood into the brain parenchyma or subarachnoid space with associated neurologic symptoms	90±7 days
proportion of organs hemorrhage	including gastrointestinal bleeding and mucocutaneous hemorrhage	90±7 days
death	death due to any cause	90±7 days

Collaborators and Investigators

• Sponsor: General Hospital of Shenyang Military Region

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2017
• Primary Completion (Actual): October 8, 2018
• Study Completion (Actual): January 8, 2019

Study Registration Dates

• First Submitted: April 27, 2018
• First Submitted That Met QC Criteria: May 29, 2018
• First Posted (Actual): June 11, 2018

Study Record Updates

• Last Update Posted (Actual): July 22, 2020
• Last Update Submitted That Met QC Criteria: July 20, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Ischemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Argatroban
• Other Study ID Numbers: k(2017)38

Drug and device information, study documents

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