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)

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 the NS group and the control group randomly after confirming as acute ischemic stroke (AIS). In the NS group, the patient will undergo NS 2000ml intravenous infusion immediately after IVT, with the speed of 200ml/h. In the control group, the patient will receive an NS 200-400ml 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 0-2), or an unfavorable outcome (a score of 3 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.

Study Overview

• Status: Completed
• Conditions: Brain Infarct
• Intervention / Treatment: Drug: 0.9% NaCl 2000ml; Drug: 0.9% NaCl 200-400ml

• Study Type: Interventional
• Enrollment (Actual): 241
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Heibei
    • Cangzhou, Heibei, China, 061014
      • Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine of Hebei Province
  • Jiangxi
    • Jiujiang, Jiangxi, China, 332000
      • Affiliated Hospital of Jiujiang University
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Tianjin Medical University General Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria

1. AIS;
2. Age 18-80 years;
3. Prestroke mRS≤1;
4. NIHSS score 0-25;
5. Onset-to-needle time≤4.5 h;
6. Sign the informed consent. Exclusion criteria

(1) Massive infarction, characterized by infarction area larger than 1/3 of the effected middle cerebral artery territory and/or the cerebellum territory presented in admitted computed tomography (CT) or MRI; (2) Intention to undergo endovascular treatment; (3) History of heart failure or pre-IVT BNP≥500pg/ml or having presentations or signs indicating heart failure; (4) Haemorrhage during IVT, including ICH, severe digestive haemorrhage and severe respiratory haemorrhage; (5) Allergy to thrombolysis drugs; (6) Intolerant to thrombolysis due to any reasons and had to terminate thrombolysis; (7) 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; (8) Cerebral infarction or myocardial infarction within previous 3 months, previous intracranial haemorrhage (ICH) including parenchymal haemorrhage, intraventricular haemorrhage, subarachnoid haemorrhage, subdural/external haematoma, etc; (9) Severe brain trauma, intracranial or intraspinal surgery within previous 3 months or known malignant intracranial neoplasm, giant intracranial aneurysm or arteriovenous malformation; (10) Persistent systolic blood pressure≥180mmHg or diastolic blood pressure≥100mmHg; (11) Admitted blood glucose<2.8mmol/L or >22.22mmol/L; (12) 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; (13) Known defect of platelet or clotting function, platelet count<100×109/L; (14) Stroke mimics, such as seizure and hysteria; (15) Brain haemorrhage identified by CT or MRI; (16) Any terminal illness such that patients would not be expected to survive>1 year; (17) Pregnant women or nursing mother; (18) Poor compliance, or inability to adhere to the trial protocol or follow-up; (19) 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
Placebo Comparator: Control group; The patient will the patients receive an NS 200-400ml after IVT.	Drug: 0.9% NaCl 200-400ml; The patients receive an NS 200-400ml after IVT. Subsequent therapy is based on Chinese guidelines for diagnosis and treatment of acute ischemic stroke 2018. All of the subjects should be treated in the hospital at least 7 days according to the guidelines for early management of stroke.
Experimental: NS group; The patient will undergo NS 2000ml intravenous infusion immediately after IVT.	Drug: 0.9% NaCl 2000ml; The patient will undergo NS 2000ml intravenous infusion immediately after IVT. Subsequent therapy is based on Chinese guidelines for diagnosis and treatment of acute ischemic stroke 2018. All of the subjects should be treated in the hospital at least 7 days according to the guidelines for early management of stroke.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With 90-day Favorable Outcome	Disability on day 90, as scored by means of the modified Rankin scale (mRS), dichotomized as a favorable outcome (a score of 0 to 2), or an unfavorable outcome (a score of 3 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
Platelet-to-lymphocyte (PLR)	Peripheral blood inflammatory indices, platelet-to-lymphocyte (PLR) at 24-48 hours after randomization.	24-48 hours
SII	Peripheral blood inflammatory indices, (platelet✖neurophil)/lymphocyte (SII) at 24-48 hours after randomization.	24-48 hours
S100-β	Laboratory examinations, peripehral S100-β at 24-48 hours after randomization.	24-48 hours
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 on Day 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 on Day 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 on Day 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
Number of Participants With Barthel Index 60-100 on Day 30	The Barthel Index represents functional status at follow-up time, the scores of which range from 0 (complete dependence) to 100 (complete independence) measured by several items, including feeding, bathing, grooming, dressing, bowels, bladder, toilet use, transfers, and stairs.	30 days
Number of Participants With Barthel Index 60-100 on Day 90	The Barthel Index represents functional status at follow-up time, the scores of which range from 0 (complete dependence) to 100 (complete independence) measured by several items, including feeding, bathing, grooming, dressing, bowels, bladder, toilet use, transfers, and stairs.	90 days
Number of Pariticipants With Early Neurological Deterioration (END, △NIHSS≥2)	Early neurological deterioration (END) indicates an increase of ≥2 in 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
Number of Participants With Early Neurological Deterioration (END, △NIHSS≥4)	Early neurological deterioration (END) indicates an increase of ≥4 in 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
Imaging Infarction Volume at 24 Hours	Cranial computed tomography (CT) scans are performed before IVT and 24 hours after randomization. The infarction area is confirmed using CT maps and the infarction volume is calculated by 3D-Slicer (Version4.6.2, https://www.slicer.org/).	24 hours
Blood Pressure at 24 Hours	Blood pressure, including systolic blood pressure (SBP) and diastolic blood pressure (DBP), is monitored at 24 hours after randomization.	24 hours
Ejection Fraction	Ejection fraction was assessed by ultrasonic cardiogram within 72 hours after randomization.	72 hours
Death Rate	Death rate within 90 days after randomization.	90 days
Number of Paricipants With Intracaranial Hemorrhage	Intracaranial hemorrhage confirmed by cranial CT within 7 days after randomization.	7 days
Number of Participants With Symptomatic Intracranial Hemorrhage	Symptomatic intracranial hemorrhage indicates NIHSS deterioration≥2 scores in combination with intracranial hemorrhage on CT scan without other causes for the deterioration within 7 days after randomization.	7 days
Neutrophil-to-lymphocyte Ratio (NLR)	Peripheral blood inflammatory indices, neutrophil-to-lymphocyte ratio (NLR),24-48 hours after randomization.	24-48 hours
Myeloperoxidase (MPO)	Laboratory examinations, peripheral myeloperoxidase (MPO) at 24-48 hours after randomization.	24-48 hours
Brain Derived Neurotrophic Factor (BDNF)	Laboratory examinations, brain derived neurotrophic factor (BDNF)at 24-48 hours after randomization.	24-48 hours

Collaborators and Investigators

• Sponsor: Tianjin Medical University General Hospital
• Collaborators: Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine; Affliated Hospital of Jiujiang University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Actual): December 20, 2024
• Study Completion (Actual): January 8, 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): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 5, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

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

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
• product manufactured in and exported from the U.S.: No