Efficacy Argatroban in Ischemic Stroke With Early Deterioration (EASE)

NCT04275180 | Completed Phase 4 DMC

• 1 other identifier: Yan-2019-293
• Study Type: interventional
• Target: 628
• Locations: 1 country
• Sites: 6

Brief Summary

Acute ischemic stroke (AIS) has the characteristics of high morbidity, high mortality, high disability rate and high recurrence rate. Progressive cerebral infarction (PIS) is a subtype of AIS, accounting for 10% - 40%. Because of the gradual aggravation of neurological deficit symptoms, it has a higher rate of disability and death, which brings heavy mental and economic burden to families, society and the country. The progress of acute cerebral infarction is generally within 6 hours to 1 week after the onset of the disease. At present, it is considered that thrombus prolongation is one of the important pathogenesis of PIS. Heparin can reduce the incidence of post-stroke embolism, but its benefits are offset by the risk of hemorrhage due to the high risk of hemorrhage. The 2013AHA guidelines in the United States do not recommend it as a routine anticoagulant therapy. Therefore, reducing the risk of bleeding is the key to the anticoagulation therapy of PIS. Argatroban is a new thrombin inhibitor. Its mechanism of action is to bind and inactivate thrombin (factor Ⅱ a) directly.Compared with traditional anticoagulants, argatroban not only has the advantages of good anticoagulant effect and rapid onset, but also has high safety. Therefore, this study aims to verify the clinical efficacy of Argatroban in the treatment of PIS in a large population. In this study, 628 patients are expected to be enrolled into the study group. The experimental group and the control group are selected by dynamic random method. Both groups are given standard medical treatment, including routine antiplatelet, blood pressure control, statins to stabilize plaque, etc. The control group is only given standard medical treatment. In the experimental group, Argatroban is used on the basis of standard medical treatment. Both groups are treated for 7 days, and the second-class prevention standard medical treatment is given from the 8th to the 90th day. The main outcome measure is the good prognosis rate at the third month after PIS. The good prognosis was defined as the modified Rankin Scale (mRS) ≤ 3.

Conditions

Acute Progressive Ischemic Stroke

Outcome Measures

Primary Outcomes (1)

• proportion of patients with a 3-month modified Rankin Scale (mRS) score≤ 3

  mRS 0-6, higher indicate worse outcome

  3 months

Secondary Outcomes (5)

• proportion of patients with a 3-month modified Rankin Scale (mRS) score≤ 2

  3 months

• mRS score in the third month of PIS

  3 months

• National Institute of Health stroke scale(NIHSS) scores in the third months of PIS

  3 months

• The rate of composite events in the third months of PIS, including cerebrovascular events, myocardial infarction, angina pectoris and systemic embolism

  3 months

• Recent changes in living ability, Barthel Index in the third months

  3 months

Other Outcomes (3)

• Symptomatic hemorrhage transformation within 7 days after PIS

  7 days

• Parenchymal hemorrhage within 7 days after PIS

  7 days

• Adverse reactions and events reported by researchers

  3 months

Study Arms (2)

control

NO INTERVENTION

Standard medical treatment, including routine antiplatelet, blood pressure control, statins to stabilize plaque, etc.

Argatroban group

EXPERIMENTAL

Argatraban is used on the basis of standard medical treatment.

Drug: Argatroban

Interventions

Argatroban DRUG

Argatroban plus standard medical treatment

Argatroban group

Eligibility Criteria

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

You may qualify if:

• AIS patients with typical symptoms and signs within 48h, including those who received intravenous thrombolysis for 24 hours.
• The neurologic function deteriorated from 6h to 48h after the onset of the disease, and the NIHSS score increased by ≥ 2 points;
• Sign informed consent.

You may not qualify if:

• The diagnosis was cardiogenic cerebral embolism;
• In the patients with large area cerebral infarction of anterior circulation, the focus area was larger than 2 / 3 of the area of cerebral hemisphere;
• Patients with NIHSS score ≥ 21;
• Patients with conversion of intracranial hemorrhage;
• Patients with tirofiban;
• Patients with blood pressure ≥ 180 / 110mmhg after treatment;
• There were severe heart, liver and kidney dysfunction, such as LVEF \< 40%, serum AST and ALT increased to 3 times of the upper limit of normal, creatinine clearance \< 30ml / min;
• Patients with hematological diseases and those with bleeding tendency;
• In the past 6 months, the patients had a history of severe gastrointestinal hemorrhage;
• Allergic to argatraban;
• Patients (such as those with mental and mental disorders) who are not suitable for the clinical study.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (6)

Min Lou

Hangzhou, Zhejiang, 310000, China

Location

People's Hospital of Anji

Anji, China

Location

Jiaxing Second Hospital

Jiaxing, China

Location

Ninghai First Hospital

Ninghai, China

Location

Quzhou Kecheng People's Hospital

Quzhou, China

Location

Tongxiang Diyi Renmin Hospital

Tongxiang, China

Location

Related Publications (1)

• Zhang X, Zhong W, Xue R, Jin H, Gong X, Huang Y, Chen F, Chen M, Gu L, Ge Y, Ma X, Zhong B, Wang M, Hu H, Chen Z, Yan S, Chen Y, Wang X, Zhang X, Xu D, He Y, Lou M, Wang A, Zhang X, Ma L, Lu X, Wang J, Lou Q, Qian P, Xie G, Zhu X, He S, Hu J, Wen X, Liu Y, Wang Y, Fu J, Fan W, Liebeskind D, Yuan C, Lou M. Argatroban in Patients With Acute Ischemic Stroke With Early Neurological Deterioration: A Randomized Clinical Trial. JAMA Neurol. 2024 Feb 1;81(2):118-125. doi: 10.1001/jamaneurol.2023.5093.

  PMID: 38190136 DERIVED

MeSH Terms

Interventions

argatroban

Study Officials

• Ze Xin Chen

  2nd affiliated hospital of Zhejiang University, School of Medicine

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2020
• First Posted: February 19, 2020
• Study Start: March 21, 2020
• Primary Completion: July 31, 2022
• Study Completion: January 31, 2023
• Last Updated: April 19, 2023

Record last verified: 2023-02

Locations

CN (6)