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

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ClinicalTrials.gov Identifier: NCT02798601
Recruitment Status : Not yet recruiting
First Posted : June 14, 2016
Last Update Posted : February 22, 2019
Sponsor:
Collaborator:
CES University
Information provided by (Responsible Party):
Hospital Pablo Tobón Uribe

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.

Condition or disease Intervention/treatment Phase
Head Trauma Other: Hypernatremia Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 278 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Early Induced Hypernatremia for the Prevention and Management of Brain Edema in Patients With Severe Traumatic Brain Injury in a University Hospital
Estimated Study Start Date : January 2, 2020
Estimated Primary Completion Date : December 30, 2022
Estimated Study Completion Date : December 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Edema

Arm Intervention/treatment
Experimental: Hypernatremia
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.
Other: Hypernatremia
Serum Sodium goal: 150 - 155 milliequivalent/L.

No Intervention: Normonatremia
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.



Primary Outcome Measures :
  1. Glasgow Outcome Scale Extended [ Time Frame: 6 months ]
    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 :
  1. All-cause mortality [ Time Frame: 28 - day AND 180 - day mortality ]
    Mortality by any cause

  2. Ventilator - Free Days [ Time Frame: 30 days ]
    Days free of mechanical ventilation at 30 days

  3. Fluid balance. [ Time Frame: 5 days ]
    Net fluid balance (input minus output) (ml) at day 1,2,3,4 y 5.

  4. Acute kidney injury [ Time Frame: 7 days ]

    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.


  5. Intracranial pressure (ICP) measurement [ Time Frame: 5 days ]
    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.

  6. Need of second line therapies for brain edema [ Time Frame: 7 days ]
    Secondary decompressive craniectomy or barbituric coma for control of brain edema.

  7. All-cause mortality according to subgroups of monitoring: guided by neurologic examination and serial CT imaging or guided by intracranial pressure monitoring. [ Time Frame: 28 - day AND 180 - day mortality ]
    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).

  8. Glasgow Outcome Scale Extended (GOSE) according to subgroups of monitoring: guided by neurologic examination and serial CT imaging or guided by intracranial pressure monitoring. [ Time Frame: 6 Months ]
    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).



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Ages Eligible for Study:   14 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02798601


Contacts
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Contact: Jorge H Donado, MD, MSc 574- 4459000 ext 9897 jdonado@hptu.org.co
Contact: Gisela De La Rosa, MD 574- 4459000 ext 9597 giseladlr@gmail.com

Sponsors and Collaborators
Hospital Pablo Tobón Uribe
CES University
Investigators
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Principal Investigator: Juan C Lopez de Mesa, MD Hospital Pablo Tobon Uribe

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Responsible Party: Hospital Pablo Tobón Uribe
ClinicalTrials.gov Identifier: NCT02798601     History of Changes
Other Study ID Numbers: U1111-1183-0891
HPTU ( Registry Identifier: 2016.049 )
First Posted: June 14, 2016    Key Record Dates
Last Update Posted: February 22, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hospital Pablo Tobón Uribe:
Cerebral edema
Hypernatremia
Extended Glasgow Outcome Scale
Intracranial pressure
Mannitol
Hypertonic saline
Mortality
Additional relevant MeSH terms:
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Craniocerebral Trauma
Brain Edema
Hypernatremia
Trauma, Nervous System
Nervous System Diseases
Wounds and Injuries
Brain Diseases
Central Nervous System Diseases
Water-Electrolyte Imbalance
Metabolic Diseases
Mannitol
Diuretics, Osmotic
Diuretics
Natriuretic Agents
Physiological Effects of Drugs