Normal Saline Infusion for Stroke After Intravenous Thrombolysis

Study Overview
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Brief Summary
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This study aims to explore the safety and efficacy of 0.9% normal saline （NS） infusion on stroke after intravenous thrombolysis (IVT), we decided to conduct this multi-centre randomized controlled trial for the first time. This trial will provide an innovative strategy to facilitate functional independence after stroke administered with IVT. This is a multi-center, randomized controlled two arm (1:1 ratio) clinical trial. The enrolled participators will be divided into NS group and control group randomly after confirming as acute ischemic stroke (AIS) according to symptoms and signs. In NS group, the patient will undergo NS 2000ml intravenous infusion swiftly after IVT, with the speed of 200ml/h. In control group, the patient will not undergo NS intravenous infusion after IVT. The primary efficacy is disability at days 90, as scored by means of the modified Rankin scale (mRS), dichotomized as a favorable outcome (a score of 0 or 1), or an unfavorable outcome (a score of 2 to 6). The secondary outcomes mainly comprise neurological deficits, disability, imaging and laboratory tests at each follow-up time. The safety outcomes include the cerebral edema at 24-hour post-IVT detected by cranial CT, the 24-hour fluctuation of blood pressure and the cardiac function detected by ultrasonic cardiogram within 3 days after IVT. Stata 15.1 and R software will be used for statistical analysis

Official Title
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Safety and Efficacy of Immediate Normal Saline Infusion for Stroke After Intravenous Thrombolysis (NS-STAR): a Protocol of Randomized Controlled Trial

Conditions
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Brain Infarct

Intervention / Treatment
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* Drug: 0.9% NaCl 2000ml
* Drug: 0.9% NaCl 0ml


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria： Acute ischemic stroke (AIS) Age 18-80 years Pre-stroke mRS≤1 Onset-to-needle time≤4.5 hours Treated with alteplase Initial diagnosis of penetrating artery disease, large artery atherosclerosis (LAA) inducing parent artery (plaque or thrombus) occluding penetrating artery and LAA inducing hypoperfusion defined by Chinese ischemic stroke subclassification (CISS) system Sign the informed consent Exclusion Criteria： Severe AIS, including NIHSS score>20 in dominant hemisphere infarction, or NIHSS score>15 in non-dominant hemisphere infarction, or NIHSS consciousness score >1 Massive infarction, characterized by infarction area larger than 1/3 of the effected middle cerebral artery (MCA) territory and/or the cerebellum territory presented in admitted CT or MRI Initial diagnosis of LAA inducing artery-to-artery embolism, cardiogenic stroke, other etiologies and undetermined etiologies defined by CISS system Intention to undergo endovascular treatment Intention to undergo antiplatelet drugs within 24 hours after IVT, such as aspirin, clopidogrel, ticagrelor, cilostazol and tirofiban Allergy to alteplase Arterial puncture at a non-compressible site within previous 7 days, major surgery within previous 14 days, sever trauma, gastrointestinal or urinary tract bleeding within previous 21 days Cerebral infarction or myocardial infarction within previous 3 months, previous intracranial haemorrhage (ICH) including parenchymal haemorrhage, intraventricular haemorrhage, subarachnoid haemorrhage, subdural/external haematoma, etc Severe brain trauma, intracranial or intraspinal surgery within previous 3 months or known malignant intracranial neoplasm, giant intracranial aneurysm or arteriovenous malformation Persistent systolic blood pressure≥180mmHg or diastolic blood pressure≥100mmHg Admitted blood glucose<2.8mmol/L or >22.22mmol/L Defect in coagulation, for example, current use of oral warfarin with an international normalised ratio>1.7, or prothrombin time>15s, or heparins during the last 48 hours, or use of direct thrombin inhibitors or direct factor Xa inhibitors during the last 48 hours or with an elevated activated partial thromboplastin time Platelet count<100×109/L Stroke mimics, such as seizure and hysteria Brain haemorrhage identified by CT or MRI Any terminal illness such that patients would not be expected to survive>1 year Pregnant women or nursing mother Poor compliance Participating in other clinical trials within previous 3 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NS group<br>The patient will undergo NS 2000ml intravenous infusion swiftly after IVT. | Drug: 0.9% NaCl 2000ml<br>* The patient will undergo NS 2000ml intravenous infusion swiftly after IVT.<br>|
| Placebo Comparator: Control group<br>The patient will not undergo 0.9% NaCl intravenous infusion after IVT. | Drug: 0.9% NaCl 0ml<br>* The patient will not undergo 0.9% NaCl intravenous infusion after IVT.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 90-day favorable outcome | Disability at days 90, as scored by means of the modified Rankin scale (mRS), dichotomized as a favorable outcome (a score of 0 or 1), or an unfavorable outcome (a score of 2 to 6). Scores on mRS range from 0 (no symptoms at all) to 6 (death), with higher values reflecting more severe disability or death. | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NIHSS scores at 24 hours | The National Institutes of Health Stroke Scale (NIHSS), a 15-item scale that measures the level of neurologic impairment. Total scores on the NIHSS range from 0 to 42, with higher values reflecting more severe cerebral infarcts (<5, mild impairment; ≥25, very severe neurologic impairment). | 24 hours | 
| NIHSS scores at days 7 | The National Institutes of Health Stroke Scale (NIHSS), a 15-item scale that measures the level of neurologic impairment. Total scores on the NIHSS range from 0 to 42, with higher values reflecting more severe cerebral infarcts (<5, mild impairment; ≥25, very severe neurologic impairment). | 7 days | 
| mRS at days 7 | Scores on the modified Rankin scale(mRS) range from 0 (no symptoms at all) to 6 (death), with higher values reflecting more severe disability or death. | 7 days | 
| mRS at days 30 | Scores on the modified Rankin scale(mRS) range from 0 (no symptoms at all) to 6 (death), with higher values reflecting more severe disability or death. | 30 days | 
| volume of infarction at 24 hours |  | 24 hours | 
| early neurological deterioration | Early neurological deterioration indicates an increase of 4 or more points on the NIHSS score within 24 hours after IVT, and the deterioration is not caused by intracranial hemorrhage that is confirmed by cranial CT. The National Institutes of Health Stroke Scale (NIHSS), a 15-item scale that measures the level of neurologic impairment. Total scores on the NIHSS range from 0 to 42, with higher values reflecting more severe cerebral infarcts. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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brian infarction, thrombolysis, haemodilution, normal saline