Neutral Versus Liberal fLuId In Traumatic Brain Injury: a Randomised Controlled Trial (LIMIT)

The Effect of Neutral Versus Liberal fLuId Balance In TraumaTic Brain Injury: a Randomised Phase II Feasibility Controlled Trial

Feasibility and safety of targeting neutral vs liberal fluid balance in traumatic brain injured patients: a phase II randomized controlled trial

Study Overview

• Status: Not yet recruiting
• Conditions: Traumatic Brain Injury; Fluid Overload; Outcome, Fatal
• Intervention / Treatment: Procedure: fluid balance

Detailed Description

To determine whether a zero fluid balance strategy during the first week compared to a more liberal fluid policy (allowing positive balance) is feasible in adult intensive care unit (ICU) patients with traumatic brain injury (TBI).Participants randomized to neutral fluid balance will be assessed daily with the aim to maintain a mean daily fluid balance of 0 over the course of the first 5 days from randomization (maximum at day 7 of ICU stay). In case of need for augmentation of cerebral perfusion pressure with 0 balance, fluids will be allowed according to a predefined protocol (see further).Participants randomized to the control group will receive the standard fluid management required as determined by the treating team. Fluid strategy as randomised should be applied for at least 5 days from randomization.

Primary aim: ● Feasibility: ability to achieve a daily neutral balance (0 +/- 500 ml) in the intervention group.

Secondary aims:● Incidence of renal complications, including acute kidney injury, need for renal replacement, multiorgan failure

• Respiratory complications including reduced partial pressure of oxygen/ fraction of inspired oxygen (P/F) ratio
• Cardiopulmonary complications, i.e myocardial infarction, cardiac failure, cardiac arrhythmias, ventricular or supraventricular, pulmonary oedema, ventilator associated pneumonia, acute respiratory distress syndrome
• Difference in mean and daily CPP among the groups
• Difference in daily fluid balance and fluid input during the first 7 days after ICU admission
• Total and daily dose of vasopressors and diuretics during ICU stay
• Vasopressor-free days up to 28 days from ICU admission
• ICU-free days up to 28 days
• Ventilator-free days up to 28 days from intubation.
• Maximum Therapy intensity level (TIL) during the 5 days of randomization

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chiara Robba, PhD; Phone Number: 3473912338; Email: kiarobba@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adult patients with TBI (isolated or with extracranial injuries, with and without ICP monitoring)
• Admitted to intensive care unit
• Age >18 years
• Enrolment <48h after ICU admission

Exclusion Criteria:

• Enrolled in another clinical trial that is unapproved for co-enrolment
• Pregnant or suspected pregnancy
• Concomitant hemorrhagic shock expected to require surgical treatment in the following 24h from inclusion or requiring polytransfusions (> 6 blood products or massive transfusion protocol)
• Hemodynamic instability (HR > 120 despite fluid resuscitation of at least 1 liter, and systolic blood pressure < 90 mmHg) at the ICU admission requiring high dosage of norepinephrine (> 0.5 mcg/kg/min) or inotropes (any dose)

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
No Intervention: Standard of care group; Patients will receive fluids according to clinical practice
Active Comparator: Neutral balance; Patients will receive fluids aiming to a neutral balance	Procedure: fluid balance; patients will receive fluids with the aim to achieve a neutral balance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility- rate of patients able to achieve neutral fluid balance( 0 +/- 500 ml) during the first week from ICU admission	Ability to target and achieve a daily and total neutral fluid balance (0 +/- 500 ml) in the intervention group. In particular,testing the hypothesis of whether all pairwise differences between group means are the same in a design of repeated measures with 7 days points. We hypothesise a mean of 0 ml in the conservative group, a mean of 1000 ml in the liberal group and standard deviation in the population of 850 ml (500 ml in the conservative group and 1000 ml in the liberal group)	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety to achieve neutral balance, i.e. the estimation of the difference of incidence of renal, pulmonary, cardiac complications between the two arms	Complications occurring during the ICU stay	From date of randomization until the date of intensive care unit discharge or death assessed up to 6 months
Rates of patients who die and experience poor neurological outcome after 6 months from ICU admission	at 6 months, at hospital and ICU discharge	6 months from ICU admission and enrolment

Collaborators and Investigators

• Sponsor: Universita degli Studi di Genova

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2023
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: July 12, 2023
• First Submitted That Met QC Criteria: August 6, 2023
• First Posted (Actual): August 9, 2023

Study Record Updates

• Last Update Posted (Actual): August 9, 2023
• Last Update Submitted That Met QC Criteria: August 6, 2023
• Last Verified: August 1, 2023

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; Wounds and Injuries; Brain Injuries, Traumatic
• Other Study ID Numbers: 001 (Buy Pharma Ecza Deposu San. Tic. Ltd.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD will be available
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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