Argatroban Plus R-tPA for Acute Ischemic Stroke

Argatroban Plus R-tPA for Acute Ischemic Stroke: a Prospective, Random, Open Label, Blinded Assessment of Outcome Multi-center Study

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.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Drug: rt-PA; Drug: Argatroban

• Study Type: Interventional
• Enrollment (Actual): 808
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • ShenYang, China
    • 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. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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%)	Drug: rt-PA; Intravenous throbolysis with 0.9mg/kg rtPA; 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%)
ACTIVE_COMPARATOR: rt-PA; Drug: rt-PA Intravenous throbolysis with 0.9mg/kg rtPA.	Drug: rt-PA; Intravenous throbolysis with 0.9mg/kg rtPA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of mRS (0-1）	90±7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of mRS (0-2）		90±7 days
symptomatic intracranial hemorrhage		48 hours
proportion of more than 2 decrease in NIHSS score	NIHSS, National Institute of Health stroke scale	48 hours
proportion of early neurological deterioration	Early neurological deterioration, defined as more than 4 increase in National Institute of Health stroke scale score	48 hours
Vascular Events	The occurence of stroke or other vascular events	90±7 days

Collaborators and Investigators

• Sponsor: General Hospital of Shenyang Military Region

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 21, 2018
• Primary Completion (ACTUAL): January 30, 2022
• Study Completion (ACTUAL): January 30, 2022

Study Registration Dates

• First Submitted: November 12, 2018
• First Submitted That Met QC Criteria: November 12, 2018
• First Posted (ACTUAL): November 14, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 22, 2022
• Last Update Submitted That Met QC Criteria: February 20, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Argatroban
• Other Study ID Numbers: k （2018）45

Drug and device information, study documents

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