Normal Saline Infusion After Intravenous Thrombolysis in Stroke

Safety and Efficacy of Immediate Abundant Intravenous Normal Saline Infusion for Stroke After Intravenous Thrombolysis: a Multi-centre Randomized Controlled Phase III Trial

The intravenous administration of abundant normal saline is an easy-to-use strategy commonly employed to expand the blood volume. This study aimed to evaluate the efficacy and safety of the early administration of an abundant normal saline infusion after intravenous thrombolysis for promoting functional independence in patients with acute ischemic stroke. This multicenter, randomized, phase III clinical trial intends to enroll stroke participants who have undergone intravenous thrombolysis. Eligible patients are randomized to receive either abundant intravenous normal saline infusion (2,000-2,500 mL; normal saline group) or a small volume of intravenous normal saline infusion (≤600 mL; control group) immediately after thrombolysis. The primary outcome is the comparison of the ordinal modified Rankin Scale score at 90 days (±3) after randomization between the treatment groups.

Study Overview

• Status: Not yet recruiting
• Conditions: Brain Infarction
• Intervention / Treatment: Drug: normal saline; Drug: normal saline

• Study Type: Interventional
• Enrollment (Estimated): 752
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jiayue Ding, MD.; Phone Number: +86 18518347837; Email: sjnkzz2@163.com

Study Locations

• China
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, 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. Age 18 to 80 years.
2. Acute ischemic stroke treated with intravenous thrombolysis.
3. Prestroke mordified Rankin Scale score ≤1;
4. Admission NIHSS score 4-25, with NIHSS 4-5 requiring the presence of a disabling deficit as defined in the 2026 AHA/ASA Guideline for the Early Management of Patients With Acute Ischemic Stroke.
5. Onset-to-needle time≤4.5 hours or DWI-FLAIR mismatch (guided by MRI evaluation) for patients with uncertain stroke onset time according to the inclusion criteria of the WAKE-UP study.
6. Signed informed consent.

Exclusion Criteria:

1. Contraindications to intravenous thrombolysis.
2. Planned endovascular treatment prior to enrollment.
3. History of heart failure, or pre-enrollment brain natriuretic peptide (BNP) ≥100 pg/mL, or clinical presentations or signs suggestive of heart failure.
4. History of atrial fibrillation, or pre-enrollment electrocardiogram indicating atrial fibrillation.
5. History of valvular heart disease or valve replacement surgery, suggesting cardioembolic stroke.
6. History of renal dysfunction, or pre-enrollment serum creatinine >133 μmol/L, or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m².
7. Severe hemorrhage prior to enrollment, including symptomatic intracranial hemorrhage, gastrointestinal bleeding, respiratory tract bleeding, or massive skin and mucous membrane bleeding.
8. Premature termination of intravenous thrombolysis due to any reason, such as hemorrhage, allergic reaction, or seizure.
9. Participation in another clinical trial within the previous 3 months.
10. Poor compliance, or inability to adhere to the trial protocol or complete follow-up.

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
Sham Comparator: Control group	Drug: normal saline; The participants will undergo 2,000-2,500 mL normal saline intravenous infusion immediately after intravenous thrombolysis.; Drug: normal saline; The participants will receive ≤600 mL of normal saline infusion after intravenous thrombolysis.
Experimental: Normal saline group	Drug: normal saline; The participants will undergo 2,000-2,500 mL normal saline intravenous infusion immediately after intravenous thrombolysis.; Drug: normal saline; The participants will receive ≤600 mL of normal saline infusion after intravenous thrombolysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The modified Rankin Scale distribution	The ordinal scores on the modified Rankin Scale range from 0 to 6, with higher scores indicating worse outcomes.	90 days (±3)

Collaborators and Investigators

• Sponsor: Tianjin Medical University General Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: March 23, 2026
• First Submitted That Met QC Criteria: March 23, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 19, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: thrombolysis; brain infarction; normal saline; 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; Pathological Conditions, Signs and Symptoms; Brain Infarction; Pharmaceutical Preparations; Crystalloid Solutions; Isotonic Solutions; Solutions; Saline Solution
• Other Study ID Numbers: NS-STROKE-2

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