Argatroban Plus R-tPA for Acute Ischemic Stroke

NCT03740958 | Completed Phase 4 DMC

• 1 other identifier: k （2018）45
• Study Type: interventional
• Target: 808
• Locations: 1 country
• Sites: 1

Brief Summary

Acute ischemic stroke (AIS) is the most common type of stroke, which has high rate of morbidity, mortality and disability. A large number of studies have confirmed that the thrombolytic therapy can effectively open blood vessels and improve the functional prognosis of acute ischemic stroke. Therefore, all guidelines recommend intravenous thrombolysis as the first treatment of ischemic stroke patients within 4.5 hours of onset. However, about 1/3 patients receiving thrombolysis will have good prognosis, while a large number of patients will still be disabled and even dead. How to improve the neurological prognosis of thrombolytic patients has been a hot topic in the world. Recent studies have found that the combined application of argatroban and rt-PA in the treatment of AIS might improve the clinical prognosis and not significantly increase bleeding. Some studies have reported that the combined application of argatroban and rt-PA could improve the blood vessel opening rate, and prevent re-occlusion after opening. Based on the discussion, the present study is designed to explore the efficacy and safety of argatroban plus rt-PA in the treatment of AIS.

Conditions

Stroke

Outcome Measures

Primary Outcomes (1)

• Proportion of mRS (0-1）

  90±7 days

Secondary Outcomes (5)

• Proportion of mRS (0-2）

  90±7 days

• proportion of more than 2 decrease in NIHSS score

  48 hours

• proportion of early neurological deterioration

  48 hours

• Vascular Events

  90±7 days

• symptomatic intracranial hemorrhage

  48 hours

Study Arms (2)

Argatroban combined with rt-PA

EXPERIMENTAL

Drug: Argatroban combined with rt-PA Argatroban as a 100 ug/kg bolus over 3 to 5 minutes was administered intravenously within 1 hour of the tPA bolus followed by a continuous Argatroban infusion of 1.0 ug/kg per minute for 48 hours adjusted to a target activated partial thromboplastin time of 1.75 X baseline (about 10%)

Drug: rt-PA; Drug: Argatroban

rt-PA

ACTIVE COMPARATOR

Drug: rt-PA Intravenous throbolysis with 0.9mg/kg rtPA.

Drug: rt-PA

Interventions

rt-PA DRUG

Intravenous throbolysis with 0.9mg/kg rtPA

Argatroban combined with rt-PA; rt-PA

Argatroban DRUG

100 ug/kg bolus over 3 to 5 minutes was administered intravenously, followed by a continuous Argatroban infusion of 1.0 ug/kg per minute for 48 hours adjusted to a target activated partial thromboplastin time of 1.75 X baseline (about 10%)

Argatroban combined with rt-PA

Eligibility Criteria

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

You may qualify if:

• years old;
• Time from onset to treatment ≤4.5 hours;
• NIHSS ≥ 6
• Diagnosis of ischemic stroke
• Signed informed consent by patient self or legally authorized representatives.

You may not qualify if:

• mRS≥2;
• History of stroke within 3 months;
• History of intracranial hemorrhage;
• Suspected subarachnoid hemorrhage;
• Intracranial tumour, vascular malformation or arterial aneurysm;
• Major surgery within 1 month;
• Systolic pressure ≥180 mmHg or diastolic pressure ≥110 mmHg;
• Platelet count \< 105/mm3;
• Heparin therapy or oral anticoagulation therapy within 48 hours;
• Abnormal APTT;
• Thrombin or Xa factor inhibitor;
• Severe disease with a life expectancy of less than 3 months;
• Blood glucose \< 50 mg/dL (2.7mmol/L);
• Patients who have received any other investigational drug or device within 3 months;
• Pregnancy;

Sponsors & Collaborators

• General Hospital of Shenyang Military Region: lead

Study Sites (1)

General Hospital of ShenYang Military Region

Shenyang, China

Location

Related Publications (3)

• Cui Y, Wang EQ, Wang YH, Chen HS. Efficacy of argatroban plus alteplase according to time from onset to thrombolysis in acute ischemic stroke: a prespecified post-hoc analysis of the ARAIS trial. Front Neurol. 2025 Jun 25;16:1582513. doi: 10.3389/fneur.2025.1582513. eCollection 2025.

  PMID: 40635702 DERIVED

• Chen HS, Cui Y, Zhou ZH, Dai YJ, Li GH, Peng ZL, Zhang Y, Liu XD, Yuan ZM, Jiang CH, Yang QC, Duan YJ, Ma GB, Zhao LW, Wang RX, Sun YL, Shen L, Wang EQ, Wang LH, Feng YF, Wang FY, Zou RL, Yang HP, Wang K, Wang DL, Wang YL; ARAIS Investigators. Effect of Argatroban Plus Intravenous Alteplase vs Intravenous Alteplase Alone on Neurologic Function in Patients With Acute Ischemic Stroke: The ARAIS Randomized Clinical Trial. JAMA. 2023 Feb 28;329(8):640-650. doi: 10.1001/jama.2023.0550.

  PMID: 36757755 DERIVED

• Yang Y, Zhou Z, Pan Y, Chen H, Wang Y; ARAIS Protocol Steering Group. Randomized trial of argatroban plus recombinant tissue-type plasminogen activator for acute ischemic stroke (ARAIS): Rationale and design. Am Heart J. 2020 Jul;225:38-43. doi: 10.1016/j.ahj.2020.04.003. Epub 2020 Apr 8.

  PMID: 32485328 DERIVED

MeSH Terms

Conditions

Stroke

Interventions

argatroban

Condition Hierarchy (Ancestors)

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

Study Officials

• Huisheng Chen, Doctor

  Neurology Department

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department Chairman

Study Record Dates

• First Submitted: November 12, 2018
• First Posted: November 14, 2018
• Study Start: December 21, 2018
• Primary Completion: January 30, 2022
• Study Completion: January 30, 2022
• Last Updated: February 22, 2022

Record last verified: 2022-02

Locations

CN (1)