Argatroban Plus R-tPA for Acute Ischemic Stroke

NCT ID: NCT03740958

Last Updated: 2022-02-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 808 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-21
• Study Completion Date: 2022-01-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Argatroban combined with rt-PA

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%)

Group Type: EXPERIMENTAL

rt-PA

Intervention Type: DRUG

Intravenous throbolysis with 0.9mg/kg rtPA

Argatroban

Intervention Type: 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%)

rt-PA

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

Group Type: ACTIVE_COMPARATOR

rt-PA

Intervention Type: DRUG

Intravenous throbolysis with 0.9mg/kg rtPA

Interventions

rt-PA

Intravenous throbolysis with 0.9mg/kg rtPA

Intervention Type: DRUG

Argatroban

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%)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 18-80 years old;

2. Time from onset to treatment ≤4.5 hours;

3. NIHSS ≥ 6

4. Diagnosis of ischemic stroke

5. Signed informed consent by patient self or legally authorized representatives.

Exclusion Criteria

1. mRS≥2;

2. History of stroke within 3 months;

3. History of intracranial hemorrhage;

4. Suspected subarachnoid hemorrhage;

5. Intracranial tumour, vascular malformation or arterial aneurysm;

6. Major surgery within 1 month;

7. Systolic pressure ≥180 mmHg or diastolic pressure ≥110 mmHg;

8. Platelet count < 105/mm3;

9. Heparin therapy or oral anticoagulation therapy within 48 hours;

10. Abnormal APTT;

11. Thrombin or Xa factor inhibitor;

12. Severe disease with a life expectancy of less than 3 months;

13. Blood glucose < 50 mg/dL (2.7mmol/L);

14. Patients who have received any other investigational drug or device within 3 months;

15. Pregnancy;

16. Researchers consider patients inappropriate to participate in the registry.

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

Sponsors

General Hospital of Shenyang Military Region

OTHER

Sponsor Role: lead

Responsible Party

Hui-Sheng Chen

Department Chairman

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Huisheng Chen, Doctor

Role: STUDY_CHAIR

Neurology Department

Locations

General Hospital of ShenYang Military Region

Shenyang, , China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 40635702 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36757755 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32485328 (View on PubMed)

Other Identifiers

k （2018）45

Identifier Type: -

Identifier Source: org_study_id