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

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

Detailed Description
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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

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

Conditions
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Traumatic Brain Injury, Fluid Overload, Outcome, Fatal

Intervention / Treatment
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* Procedure: fluid balance


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard of care group<br>Patients will receive fluids according to clinical practice | |
| Active Comparator: Neutral balance<br>Patients will receive fluids aiming to a neutral balance | Procedure: fluid balance<br>* patients will receive fluids with the aim to achieve a neutral balance<br>|

What is the study measuring?
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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 |