Saline Versus Balanced Crystalloid in Traumatic Brain Injury (FLUID-TBI)

Saline vs. Balanced Crystalloid in Traumatic Brain Injury

The goal of this clinical trial is to determine which crystalloid (saline or balanced) should be used in the critical management of Traumatic Brain Injury (TBI) in moderate or severe TBI patients. This trial will determine whether the use of saline or balanced crystalloids is associated with improved outcomes in TBI patients.

Participants will

1. be given fluids through the veins, either saline or balanced fluid will be given.
2. From the first day to the day 14 of the hospitalization (or discharge, whichever comes first), vital signs, laboratory values, treatments given, and other medical data will be collected from the medical record.
3. Six months later, your final disability, if any, will be assessed during your follow-up with a doctor. It involves answering a short survey that will take about 5 minutes or less.

Study Overview

• Status: Recruiting
• Conditions: Traumatic Brain Injury (TBI) Patients
• Intervention / Treatment: Drug: Normal Saline (0.9% NaCl); Drug: balanced crystalloid

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Mechelle Kaufman, BSN, RN; Phone Number: 502-588-2329; Email: mechelle.kaufman@louisville.edu
• Study Contact Backup: Name: Akshitkumar Mistry, M.D.; Email: a.mistry@uoflhealth.org

Study Locations

• United States
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • University of Louisville Hospital
      • Contact: Mechelle Kaufman, BSN; Phone Number: 502-852-5992; Email: mechelle.kaufman@louisville.edu
      • Contact: Akshitkumar a.mistry@uoflhealth.org, M.D.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Trauma patients presenting to the Emergency Room for initial care
• Glasgow Coma Scale ≤ 12
• Head CT with skull fracture(s) and/or hemorrhage(s) (>1cm in any single dimension) with a reported mechanism of trauma

Exclusion Criteria:

• Severe visceral trauma dictating mortality (visceral injury severity score > brain injury severity score)
• Non-survivable brain injury based on the treating physician's judgment
• Emergent visceral operative intervention before complete trauma assessment
• Concern for ruptured intracranial vascular malformation
• Patients who are transferred from another facility

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normal Saline; normal saline (0.9% sodium chloride) administered intravenously	Drug: Normal Saline (0.9% NaCl); For the primary purpose of fluid therapy or resuscitation in the emergency room and during hospitalization. The interventions will be administered intravenously whenever isotonic intravenous fluid administration is ordered by the treating provider for fluid resuscitation and/or maintenance in the emergency room and during inpatient hospitalization. Assignment to the intervention arm will be adhered to from enrollment to discharge. The total volume, rate, initiation, cessation, and co-interventions will be left to the discretion of the treating provider. Adherence will be ensured by dual interventions at the level of pharmacy IV fluid supply and physician order. The fluids will be physically administered according to the standard intravenous procedures and those outlined in the manufacturer's instructions.
Active Comparator: Isotonic Crystalloid; balanced crystalloid intravenous fluid therapy	Drug: balanced crystalloid; For the primary purpose of fluid therapy or resuscitation in the emergency room and during hospitalization. The interventions will be administered intravenously whenever isotonic intravenous fluid administration is ordered by the treating provider for fluid resuscitation and/or maintenance in the emergency room and during inpatient hospitalization. Assignment to the intervention arm will be adhered to from enrollment to discharge. The total volume, rate, initiation, cessation, and co-interventions will be left to the discretion of the treating provider. Adherence will be ensured by dual interventions at the level of pharmacy IV fluid supply and physician order. The fluids will be physically administered according to the standard intravenous procedures and those outlined in the manufacturer's instructions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurological Outcomes	Glasgow Outcome Scale-Extended (GOSE) 8-point scale. Glasgow Outcome Scale has been widely accepted as the standard assessment scale of global outcomes after severe brain injury because it captures well how the injury affects functioning in major areas of life. Using the manual for the GOSE interview, we will conduct our primary efficacy assessment at 6 months after ICU admission in person or over the phone. Outcomes on the GOSE scale do not change past the 6-month mark in moderate and severe TBI patients. The 8-point ordinal GOSE scale for the primary efficacy assessment will be dichotomized into favorable (GOSE score 4-8) and unfavorable (GOSE 1-3) outcomes. The primary analysis model will be a logistic regression model where the outcome of interest is the dichotomized GOS-E evaluated at 6 months to reflect favorable and unfavorable outcomes. The covariate of interest is a randomization assignment.	6 months post injury

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inpatient mortality	We will assess the inpatient mortality of the participants. We will note the time from admission to death or discharge. The secondary outcome (inpatient mortality) will be analyzed using two approaches. The primary analysis model will be a logistic regression model where the outcome of interest is the vitality status (alive or dead) at discharge. The covariate of interest is a randomization assignment. The secondary analysis will be a time-to-death analysis comparing the survival curves between the two randomized groups using a log-rank test.	randomization to hospital discharge typically 2 weeks.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare delayed interventions to treat Intracranial pressure (ICP).	Surgical or medical ICP-related therapeutic interventions. Events of acute kidney injury, cerebral edema, and in-patient mortality, will be captured.	randomization to hospital discharge, typically 2 weeks.

Collaborators and Investigators

• Sponsor: University of Louisville
• Collaborators: Kentucky Spinal Cord and Head Injury Research Board
• Investigators: Principal Investigator: Akshitkumar Mistry, MD, Assistant Professor Term

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2025
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: April 9, 2025
• First Submitted That Met QC Criteria: April 23, 2025
• First Posted (Actual): May 1, 2025

Study Record Updates

• Last Update Posted (Actual): August 17, 2025
• Last Update Submitted That Met QC Criteria: August 12, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries, Traumatic; Wounds and Injuries; Brain Injuries
• Other Study ID Numbers: 24.0224

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Timeframe for sharing undecided at this early stage

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes