Safety and Efficacy of Levofloxacin Combined With Intravenous Thrombolysis for Acute Ischemic Stroke

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy and safety of levofloxacin combined with intravenous thrombolysis in treating acute ischemic stroke

Detailed Description
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Acute ischemic stroke is a leading cause of disability and mortality. Intravenous thrombolysis is a major therapy for acute ischemic stroke, however, nearly half of patients failed to benefit from it. It is necessary to find new interventions combined to intravenous thrombolysis, which promote the efficacy of intravenous thrombolysis. The investigators' previous studies suggested levofloxacin to be a newly identified neuro-protective agent, which could reduce infarct volume and improve neurologic function in animal models. To evaluate the efficacy and safety of levofloxacin combined with intravenous thrombolysis in treating acute ischemic stroke patients, the prospective, multicenter and randomized controlled trial was designed.

Official Title
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Safety and Efficacy of Levofloxacin Combined With Intravenous Thrombolysis for Acute Ischemic Stroke

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Drug: Levofloxacin
* Drug: Levofloxacin simulant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 years. Acute ischemic stroke patients underwent intravenous thrombolysis, treated with ateplase (0.9mg/kg) mRS≤1 before stroke onset, NIHSS ≥ 5 and ≤ 15，la (NIHSS) level of consciousness < 1 Exclusion Criteria: Endovascular treatment Patients using glucocorticoids, antiarrhythmic drugs (class I and class III antiarrhythmic drugs: quinidine, procaine amine, lidocaine, phenytoin sodium, verapamil, etc.), and quinolones within 14 days; Patients with other diseases that may aggravate adverse drug reactions, such as ventricular arrhythmias, prolonged QT interval (male: QTc>430ms, female: QTc>450ms), severe cardiac insufficiency (NYHA functional grade ≥ III), myasthenia gravis, peripheral neuropathy, seizures, tendon-related diseases, severe immune system-related diseases, hematological diseases, active hepatitis or cirrhosis, serious respiratory diseases; Abnormal liver and kidney function: glutamic oxaloacetic transaminase or glutamic pyruvic transaminase exceeds 3 times the upper limit of normal; Direct bilirubin or indirect bilirubin more than 3 times the normal upper limit; Blood creatinine exceeds 1.1 times the upper limit of normal; Creatinine clearance rate≤50ml/min; Urea nitrogen≥ 20mg/dL; Concurrent infection; Fasting blood glucose lower than 3.9 mmol/L; Patients with symptomatic intracranial hemorrhage confirmed by clinical signs and imaging before randomization; Patients allergy to fluoroquinolones or other antibiotics; Patients with a life expectancy less than 3 months or patients unable to complete the study for other reasons; Not willing to be followed up or poor treatment compliance; Patients who are participating in other clinical studies, or have participated in other clinical studies within 3 months before enrollment, or have participated in this study; Other conditions not suitable for enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Levofloxacin group<br>Levofloxacin 200mg twice per day is administrated. | Drug: Levofloxacin<br>* Levofloxacin is a quinolone antibiotics and newly identified neuro-protective agent. Intravenous thrombolysis is one of the treatments for acute ischemic stroke.<br>* Other names: Intravenous Thrombolysis;|
| Placebo Comparator: Levofloxacin simulant group<br>Levofloxacin simulant 200mg twice per day is administrated. | Drug: Levofloxacin simulant<br>* Levofloxacin simulant is placebo. Intravenous thrombolysis is one of the treatments for acute ischemic stroke.<br>* Other names: Intravenous Thrombolysis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| National Institute of Health stroke scale (NIHSS) | NIHSS ranged from 0 to 42, a low value represents a better outcome | in 24 hours of intravenous thrombolysis | 
| NIHSS at discharge/7 days | NIHSS ranged from 0 to 42, a low value represents a better outcome | discharge/7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemorrhagic transformation and symptomatic intracranial hemorrhage | defined by computed tomography (CT) brain scan showed bleeding and a concomitant increase in National Institute of Health stroke scale (NIHSS) score of ≥4 points. | 24h,3 days and discharge/7 days | 
| Infarct volume after 3 days of Levofloxacin/simulant treatment | assessed by magnetic resonance imaging brain scan | Immediately after 3 days of Levofloxacin/simulant treatment | 
| Modified rankin scale (mRS) score at 30 days | mRS ranged from 0 to 6, a low value represents a better outcome | 30 days | 
| mRS score at 90 days | mRS ranged from 0 to 6, a low value represents a better outcome | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute ischemic stroke, Intravenous thrombolysis, Levofloxacin