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Early Induced Hypernatremia for the Prevention and Management of Brain Edema (EHIBE)

Primary Purpose

Head Trauma

Status
Withdrawn
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Hypernatremia
Sponsored by
Hospital Pablo Tobón Uribe
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head Trauma focused on measuring Cerebral edema, Hypernatremia, Extended Glasgow Outcome Scale, Intracranial pressure, Mannitol, Hypertonic saline, Mortality

Eligibility Criteria

14 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patient greater than 14 years old, who suffered severe non-penetrating Brain Trauma (Glasgow Coma Scale (GCS) equal or less than 8) and a motor GCS equal or less than 5.
  2. Criteria time: admitted to the Hospital in the first 24 hours of the Brain Trauma (BT) and admitted to ICU in the first 48 hours of brain trauma.
  3. Tomographic evidence of brain edema (one of the following criteria: deviation from the midline, obliteration of perimesencephalic cistern or altered cortico-subcortical differentiation).

Exclusion Criteria:

  1. Patient with GCS 3 and bilateral mydriatic pupils and unreactive to light, in the presence of hemodynamic stability (systolic blood pressure equal or greater than 90 mmHg).
  2. Patient with insipid diabetes at the ICU admission.
  3. Patient with limitation of therapeutic effort.
  4. Non-neurological Abbreviated Injury Score greater than 3.
  5. Patient past medical history of kidney failure, liver disease or heart failure.
  6. Serum sodium less than 135 or greater than 150 milliequivalent/L.
  7. Pregnancy.
  8. Terminal disease.
  9. No authorization to be enrolled in the trial by the patient's caregiver

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    No Intervention

    Arm Label

    Hypernatremia

    Normonatremia

    Arm Description

    Serum sodium between 150 - 155 milliequivalent/L. 7,5% sodium chloride (2 ml/kg every 4 hours), with controls of serum sodium every 4 hours, to achieve a goal of serum sodium between 150 - 155 milliequivalent/L. If after 4 doses of 7.5% sodium chloride the serum sodium is below the target, a bolus of 1 ml/kg of 12% sodium chloride will be used every 4 hours. The goal of serum sodium will be maintained for 48 hours.

    Serum sodium between 135 - 145 milliequivalent/L. Mannitol 100 ml every 4 hours for the first three days; 80 ml every 4 hours the fourth day; 60 ml every 4 hours the fifth day and 40 ml every 4 hours the sixth day and then stopping. The mannitol protocol will be interrupted at any moment if serum sodium is below 135, the systolic blood pressure is below 90 mmHg or the patient has signs of hypovolemia. In this case, 2 ml/kg of 3% sodium chloride every 4 hours will be used until the target of serum sodium is achieved and both, normovolemic state and blood pressure are restored. In addition, the mannitol protocol will be suspended when serum osmolality is above 320.

    Outcomes

    Primary Outcome Measures

    Glasgow Outcome Scale Extended
    The Extended Glasgow Outcome Scale (GOSE) is a global scale for functional outcome that rates patients into eight categories. The categories of severe disability, moderate disability and good recovery are subdivided into a lower and upper category. The scale will be used to evaluate the patient through a phone interview at 6 months of the trauma occurred. The structured interview contains nineteen specific questions which determine upper or lower levels of disability.

    Secondary Outcome Measures

    All-cause mortality
    Mortality by any cause
    Ventilator - Free Days
    Days free of mechanical ventilation at 30 days
    Fluid balance.
    Net fluid balance (input minus output) (ml) at day 1,2,3,4 y 5.
    Acute kidney injury
    Acute kidney injury (KDIGO criteria). The criteria for acute kidney injury(AKI) are based on changes in serum creatinine (SCr) and urine output. Stage I : Increase in SCr more than 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days OR increase in SCr more than 0.3 mg/dL within 48 hours OR urine output <0.5 ml/kg/h for 6-12h. Stage II : Increase in SCr between 2.0 - 2.9 times baseline, which is known or presumed to have occurred within the prior 7 days OR urine output <0.5 ml/kg/h for more than 12 hours. Stage III : Increase more than 3.0 times baseline, which is known or presumed to have occurred within the prior 7 days OR Increase in serum creatinine to 4.0 mg/dL OR Initiation of renal-replacement therapy OR urine output <0.3 ml/kg/h for more than 24 hours OR Anuria for more than 12 hours.
    Intracranial pressure (ICP) measurement
    Intracranial pressure measurement (mmHg) during the first 5 days at the ICU. Estimate the effect of therapies to control intracranial pressure. An intraparenchymal catheter will used to measure the ICP. Intracranial pressure (ICP) will be measured every hour. Intracranial hypertension will be defined as ICP > 20 mm Hg lasting longer than 5 minutes.
    Need of second line therapies for brain edema
    Secondary decompressive craniectomy or barbituric coma for control of brain edema.
    All-cause mortality according to subgroups of monitoring: guided by neurologic examination and serial CT imaging or guided by intracranial pressure monitoring.
    Estimate the effects of therapies on mortality according to subgroups of treatment (guided by neurologic examination and serial CT imaging or guided by intracranial pressure monitoring).
    Glasgow Outcome Scale Extended (GOSE) according to subgroups of monitoring: guided by neurologic examination and serial CT imaging or guided by intracranial pressure monitoring.
    Estimate the effects of therapies on the GOSE according to subgroups of treatment (guided by neurologic examination and serial CT imaging or guided by intracranial pressure monitoring).

    Full Information

    First Posted
    May 21, 2016
    Last Updated
    September 20, 2023
    Sponsor
    Hospital Pablo Tobón Uribe
    Collaborators
    CES University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02798601
    Brief Title
    Early Induced Hypernatremia for the Prevention and Management of Brain Edema
    Acronym
    EHIBE
    Official Title
    Early Induced Hypernatremia for the Prevention and Management of Brain Edema in Patients With Severe Traumatic Brain Injury in a University Hospital
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Lack of funds
    Study Start Date
    January 18, 2017 (Anticipated)
    Primary Completion Date
    January 18, 2017 (Anticipated)
    Study Completion Date
    January 18, 2018 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Hospital Pablo Tobón Uribe
    Collaborators
    CES University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The purpose of this study is to estimate the effect of an early induced hypernatremia protocol (150-155 milliequivalent/L) versus normonatremia plus mannitol (135 - 145 milliequivalent/L) in terms of neurologic outcome in patients with severe traumatic brain injury managed at critical care unit.
    Detailed Description
    Severe traumatic brain injury is one of the main causes of death in young people. Additionally, it is considered a public health problem because of the high prevalence of motor and cognitive dysfunction in those who survive. One of the cornerstones of management is the control of both intracranial pressure and brain edema. It is indicated to use osmotic active solutions to modulate the transit of fluids from the interstitial to the intracellular space. Not only mannitol but also hypertonic saline acts at this point. Currently there is no evidence in favor or against one of them. Mannitol has been usually recommended for intracranial pressure control in patients with brain trauma. However, others recommend hypertonic saline to achieve a serum sodium level of 160 milliequivalent/L to modulate brain edema. It is not clear if these therapies have an impact on the neurologic prognosis and how frequently adverse effects occur.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Head Trauma
    Keywords
    Cerebral edema, Hypernatremia, Extended Glasgow Outcome Scale, Intracranial pressure, Mannitol, Hypertonic saline, Mortality

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Hypernatremia
    Arm Type
    Experimental
    Arm Description
    Serum sodium between 150 - 155 milliequivalent/L. 7,5% sodium chloride (2 ml/kg every 4 hours), with controls of serum sodium every 4 hours, to achieve a goal of serum sodium between 150 - 155 milliequivalent/L. If after 4 doses of 7.5% sodium chloride the serum sodium is below the target, a bolus of 1 ml/kg of 12% sodium chloride will be used every 4 hours. The goal of serum sodium will be maintained for 48 hours.
    Arm Title
    Normonatremia
    Arm Type
    No Intervention
    Arm Description
    Serum sodium between 135 - 145 milliequivalent/L. Mannitol 100 ml every 4 hours for the first three days; 80 ml every 4 hours the fourth day; 60 ml every 4 hours the fifth day and 40 ml every 4 hours the sixth day and then stopping. The mannitol protocol will be interrupted at any moment if serum sodium is below 135, the systolic blood pressure is below 90 mmHg or the patient has signs of hypovolemia. In this case, 2 ml/kg of 3% sodium chloride every 4 hours will be used until the target of serum sodium is achieved and both, normovolemic state and blood pressure are restored. In addition, the mannitol protocol will be suspended when serum osmolality is above 320.
    Intervention Type
    Other
    Intervention Name(s)
    Hypernatremia
    Intervention Description
    Serum Sodium goal: 150 - 155 milliequivalent/L.
    Primary Outcome Measure Information:
    Title
    Glasgow Outcome Scale Extended
    Description
    The Extended Glasgow Outcome Scale (GOSE) is a global scale for functional outcome that rates patients into eight categories. The categories of severe disability, moderate disability and good recovery are subdivided into a lower and upper category. The scale will be used to evaluate the patient through a phone interview at 6 months of the trauma occurred. The structured interview contains nineteen specific questions which determine upper or lower levels of disability.
    Time Frame
    6 months
    Secondary Outcome Measure Information:
    Title
    All-cause mortality
    Description
    Mortality by any cause
    Time Frame
    28 - day AND 180 - day mortality
    Title
    Ventilator - Free Days
    Description
    Days free of mechanical ventilation at 30 days
    Time Frame
    30 days
    Title
    Fluid balance.
    Description
    Net fluid balance (input minus output) (ml) at day 1,2,3,4 y 5.
    Time Frame
    5 days
    Title
    Acute kidney injury
    Description
    Acute kidney injury (KDIGO criteria). The criteria for acute kidney injury(AKI) are based on changes in serum creatinine (SCr) and urine output. Stage I : Increase in SCr more than 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days OR increase in SCr more than 0.3 mg/dL within 48 hours OR urine output <0.5 ml/kg/h for 6-12h. Stage II : Increase in SCr between 2.0 - 2.9 times baseline, which is known or presumed to have occurred within the prior 7 days OR urine output <0.5 ml/kg/h for more than 12 hours. Stage III : Increase more than 3.0 times baseline, which is known or presumed to have occurred within the prior 7 days OR Increase in serum creatinine to 4.0 mg/dL OR Initiation of renal-replacement therapy OR urine output <0.3 ml/kg/h for more than 24 hours OR Anuria for more than 12 hours.
    Time Frame
    7 days
    Title
    Intracranial pressure (ICP) measurement
    Description
    Intracranial pressure measurement (mmHg) during the first 5 days at the ICU. Estimate the effect of therapies to control intracranial pressure. An intraparenchymal catheter will used to measure the ICP. Intracranial pressure (ICP) will be measured every hour. Intracranial hypertension will be defined as ICP > 20 mm Hg lasting longer than 5 minutes.
    Time Frame
    5 days
    Title
    Need of second line therapies for brain edema
    Description
    Secondary decompressive craniectomy or barbituric coma for control of brain edema.
    Time Frame
    7 days
    Title
    All-cause mortality according to subgroups of monitoring: guided by neurologic examination and serial CT imaging or guided by intracranial pressure monitoring.
    Description
    Estimate the effects of therapies on mortality according to subgroups of treatment (guided by neurologic examination and serial CT imaging or guided by intracranial pressure monitoring).
    Time Frame
    28 - day AND 180 - day mortality
    Title
    Glasgow Outcome Scale Extended (GOSE) according to subgroups of monitoring: guided by neurologic examination and serial CT imaging or guided by intracranial pressure monitoring.
    Description
    Estimate the effects of therapies on the GOSE according to subgroups of treatment (guided by neurologic examination and serial CT imaging or guided by intracranial pressure monitoring).
    Time Frame
    6 Months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    14 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Patient greater than 14 years old, who suffered severe non-penetrating Brain Trauma (Glasgow Coma Scale (GCS) equal or less than 8) and a motor GCS equal or less than 5. Criteria time: admitted to the Hospital in the first 24 hours of the Brain Trauma (BT) and admitted to ICU in the first 48 hours of brain trauma. Tomographic evidence of brain edema (one of the following criteria: deviation from the midline, obliteration of perimesencephalic cistern or altered cortico-subcortical differentiation). Exclusion Criteria: Patient with GCS 3 and bilateral mydriatic pupils and unreactive to light, in the presence of hemodynamic stability (systolic blood pressure equal or greater than 90 mmHg). Patient with insipid diabetes at the ICU admission. Patient with limitation of therapeutic effort. Non-neurological Abbreviated Injury Score greater than 3. Patient past medical history of kidney failure, liver disease or heart failure. Serum sodium less than 135 or greater than 150 milliequivalent/L. Pregnancy. Terminal disease. No authorization to be enrolled in the trial by the patient's caregiver
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Juan C Lopez de Mesa, MD
    Organizational Affiliation
    Hospital Pablo Tobon Uribe
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    Early Induced Hypernatremia for the Prevention and Management of Brain Edema

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