xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05983549</url>
    </required_header>
    <id_info>
      <org_study_id>001</org_study_id>
      <nct_id>NCT05983549</nct_id>
    </id_info>
    <brief_title>Neutral Versus Liberal fLuId In Traumatic Brain Injury: a Randomised Controlled Trial</brief_title>
    <acronym>LIMIT</acronym>
    <official_title>The Effect of Neutral Versus Liberal fLuId Balance In TraumaTic Brain Injury: a Randomised Phase II Feasibility Controlled Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Universita degli Studi di Genova</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Universita degli Studi di Genova</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Feasibility and safety of targeting neutral vs liberal fluid balance in traumatic brain&#xD;
        injured patients: a phase II randomized controlled trial&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        To determine whether a zero fluid balance strategy during the first week compared to a more&#xD;
        liberal fluid policy (allowing positive balance) is feasible in adult intensive care unit&#xD;
        (ICU) patients with traumatic brain injury (TBI).Participants randomized to neutral fluid&#xD;
        balance will be assessed daily with the aim to maintain a mean daily fluid balance of 0 over&#xD;
        the course of the first 5 days from randomization (maximum at day 7 of ICU stay). In case of&#xD;
        need for augmentation of cerebral perfusion pressure with 0 balance, fluids will be allowed&#xD;
        according to a predefined protocol (see further).Participants randomized to the control group&#xD;
        will receive the standard fluid management required as determined by the treating team. Fluid&#xD;
        strategy as randomised should be applied for at least 5 days from randomization.&#xD;
  &#xD;
        Primary aim: ● Feasibility: ability to achieve a daily neutral balance (0 +/- 500 ml) in the&#xD;
        intervention group.&#xD;
  &#xD;
        Secondary aims:● Incidence of renal complications, including acute kidney injury, need for&#xD;
        renal replacement, multiorgan failure&#xD;
  &#xD;
          -  Respiratory complications including reduced partial pressure of oxygen/ fraction of&#xD;
             inspired oxygen (P/F) ratio&#xD;
  &#xD;
          -  Cardiopulmonary complications, i.e myocardial infarction, cardiac failure, cardiac&#xD;
             arrhythmias, ventricular or supraventricular, pulmonary oedema, ventilator associated&#xD;
             pneumonia, acute respiratory distress syndrome&#xD;
  &#xD;
          -  Difference in mean and daily CPP among the groups&#xD;
  &#xD;
          -  Difference in daily fluid balance and fluid input during the first 7 days after ICU&#xD;
             admission&#xD;
  &#xD;
          -  Total and daily dose of vasopressors and diuretics during ICU stay&#xD;
  &#xD;
          -  Vasopressor-free days up to 28 days from ICU admission&#xD;
  &#xD;
          -  ICU-free days up to 28 days&#xD;
  &#xD;
          -  Ventilator-free days up to 28 days from intubation.&#xD;
  &#xD;
          -  Maximum Therapy intensity level (TIL) during the 5 days of randomization&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">September 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">May 1, 2025</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Participant, Outcomes Assessor)</masking>
      <masking_description>Participant will be blinded in knowing the arm, outcome assessors will be not involved in the study</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Feasibility- rate of patients able to achieve neutral fluid balance( 0 +/- 500 ml) during the first week from ICU admission</measure>
      <time_frame>7 days</time_frame>
      <description>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)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Safety to achieve neutral balance, i.e. the estimation of the difference of incidence of renal, pulmonary, cardiac complications between the two arms</measure>
      <time_frame>From date of randomization until the date of intensive care unit discharge or death assessed up to 6 months</time_frame>
      <description>Complications occurring during the ICU stay</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rates of patients who die and experience poor neurological outcome after 6 months from ICU admission</measure>
      <time_frame>6 months from ICU admission and enrolment</time_frame>
      <description>at 6 months, at hospital and ICU discharge</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">80</enrollment>
    <condition>Traumatic Brain Injury</condition>
    <condition>Fluid Overload</condition>
    <condition>Outcome, Fatal</condition>
    <arm_group>
      <arm_group_label>Standard of care group</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>Patients will receive fluids according to clinical practice</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Neutral balance</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Patients will receive fluids aiming to a neutral balance</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>fluid balance</intervention_name>
      <description>patients will receive fluids with the aim to achieve a neutral balance</description>
      <arm_group_label>Neutral balance</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Adult patients with TBI (isolated or with extracranial injuries, with and without ICP&#xD;
               monitoring)&#xD;
  &#xD;
            -  Admitted to intensive care unit&#xD;
  &#xD;
            -  Age &gt;18 years&#xD;
  &#xD;
            -  Enrolment &lt;48h after ICU admission&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Enrolled in another clinical trial that is unapproved for co-enrolment&#xD;
  &#xD;
            -  Pregnant or suspected pregnancy&#xD;
  &#xD;
            -  Concomitant hemorrhagic shock expected to require surgical treatment in the following&#xD;
               24h from inclusion or requiring polytransfusions (&gt; 6 blood products or massive&#xD;
               transfusion protocol)&#xD;
  &#xD;
            -  Hemodynamic instability (HR &gt; 120 despite fluid resuscitation of at least 1 liter, and&#xD;
               systolic blood pressure &lt; 90 mmHg) at the ICU admission requiring high dosage of&#xD;
               norepinephrine (&gt; 0.5 mcg/kg/min) or inotropes (any dose)&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>16 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Chiara Robba, PhD</last_name>
      <phone>3473912338</phone>
      <email>kiarobba@gmail.com</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 12, 2023</study_first_submitted>
    <study_first_submitted_qc>August 6, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>August 6, 2023</last_update_submitted>
    <last_update_submitted_qc>August 6, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 9, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Universita degli Studi di Genova</investigator_affiliation>
      <investigator_full_name>Chiara Robba</investigator_full_name>
      <investigator_title>Researcher</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Brain Injuries</mesh_term>
      <mesh_term>Brain Injuries, Traumatic</mesh_term>
      <mesh_term>Wounds and Injuries</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>IPD will be available</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05983549
  org study id: 001
  nct id: NCT05983549
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Feasibility and safety of targeting neutral vs liberal fluid balance in traumatic brain
        injured patients: a phase II randomized controlled trial
  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
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Double (Participant, Outcomes Assessor)
  masking description: Participant will be blinded in knowing the arm, outcome assessors will be not involved in the study
  measure: Feasibility- rate of patients able to achieve neutral fluid balance( 0 +/- 500 ml) during the first week from ICU admission
  time frame: 7 days
  description: 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)
  measure: Safety to achieve neutral balance, i.e. the estimation of the difference of incidence of renal, pulmonary, cardiac complications between the two arms
  time frame: From date of randomization until the date of intensive care unit discharge or death assessed up to 6 months
  description: Complications occurring during the ICU stay
  measure: Rates of patients who die and experience poor neurological outcome after 6 months from ICU admission
  time frame: 6 months from ICU admission and enrolment
  description: at 6 months, at hospital and ICU discharge
  arm group label: Standard of care group
  arm group type: No Intervention
  description: Patients will receive fluids according to clinical practice
  arm group label: Neutral balance
  arm group type: Active Comparator
  description: Patients will receive fluids aiming to a neutral balance
  intervention type: Procedure
  intervention name: fluid balance
  description: patients will receive fluids with the aim to achieve a neutral balance
  arm group label: Neutral balance
  criteria: 
  gender: All
  minimum age: 16 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Chiara Robba, PhD
  phone: 3473912338
  email: kiarobba@gmail.com
  responsible party type: Principal Investigator
  investigator affiliation: Universita degli Studi di Genova
  investigator full name: Chiara Robba
  investigator title: Researcher
  mesh term: Brain Injuries
  mesh term: Brain Injuries, Traumatic
  mesh term: Wounds and Injuries
  sharing ipd: Yes
  ipd description: IPD will be available
  ipd info type: Study Protocol