Normal Saline Infusion for Stroke After Intravenous Thrombolysis (NS-STAR)

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

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

Study Overview

• Status: Recruiting
• Conditions: Brain Infarct
• Intervention / Treatment: Drug: 0.9% NaCl 2000ml; Drug: 0.9% NaCl 0ml

• Study Type: Interventional
• Enrollment (Estimated): 128
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jiayue Ding, Prof; Phone Number: +8618518347837; Email: sjnkzz2@163.com

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Recruiting
      • Tianjin Medical University General Hospital
      • Contact: Jiayue Ding, Prof; Phone Number: +8618518347837; Email: sjnkzz2@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tianjin Medical University General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: August 3, 2023
• First Submitted That Met QC Criteria: August 12, 2023
• First Posted (Actual): August 15, 2023

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 19, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: thrombolysis; normal saline; brian infarction; haemodilution
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Stroke; Brain Infarction
• Other Study ID Numbers: NS-STAR-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will share study protocol and statistical analysis plan with other researchers.
• IPD Sharing Time Frame: One years after publications.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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