Hypertonic Saline vs. Mannitol for Elevated Intercranial Pressure

Study Overview
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Brief Summary
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This study examines the role of osmotic agents in controlling brain swelling in brain injured individuals. Two osmotic agents -- mannitol and hypertonic saline -- are in common use, and they will be compared in the context of a randomized clinical trial. The goal is to determine if these agent differ in their ability to control episodes of brain swelling.

Detailed Description
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This single-center, randomized, open label trial will compare (i) 0.9% normal saline infusion and boluses of mannitol (control group) with (ii) 3% hypertonic saline, with intermittent boluses as needed, to treat elevated intracranial pressure (ICP) following severe traumatic brain injury. Patients will be randomized to one of the two study arms following placement of an ICP monitor. Raised ICP will be defined as an ICP greater than 20 mmHG for 20 minutes or longer. In the event of such an event, the appropriate treatment will be administered. The primary endpoint will be success in ICP control, operationalized as the proportion of time during which ICP is less than or equal to 20 mmHg during the first 120 hours following initiation of monitoring. Secondary endpoints include therapy intensity level, incidence of pre-determined severe adverse events, and long-term outcomes measured at 3 and 6 months post-injury.

Official Title
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Hypertonic Saline vs. Mannitol for Elevated Intercranial Pressure

Conditions
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Traumatic Brain Injury, Elevated Intracranial Pressure

Intervention / Treatment
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* Drug: Mannitol
* Drug: Hypertonic Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: closed traumatic brain injury either (i) GCS score 3-8 (inclusive), or (ii) GCS motor score of 5 or less AND abnormal admission CT scan showing intracranial pathology hemodynamically stable with systolic blood pressure greater than 90 mmHg at least 1 reactive pupil age between 18y and 70y (inclusive) INR less than 1.5 Exclusion Criteria: actively on hypertonic saline or mannitol hypernatremia (>145 meq/L) anuric or with creatinine greater than or equal to 2.5 known seizure disorder penetrating head trauma suspected anoxic events history of, or CT confirmation of, previous brain injury any injury that, in the opinion of the Principal Investigator, has a high likelihood of death with the first 72 hours post-injury any treatment, condition, or injury that contraindicates treatment with hypertonic saline

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Mannitol<br>0.9% normal saline infusion and boluses of mannitol | Drug: Mannitol<br>* 0.9% normal saline infusion and boluses of mannitol<br>|
| Active Comparator: Hypertonic Saline<br>3% hypertonic saline continuous infusion, with intermittent boluses as needed | Drug: Hypertonic Saline<br>* 3% hypertonic saline continuous infusion, with intermittent boluses as needed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of time during which ICP is less than or equal to 20 mmHg during the first 120 hours following initiation of ICP monitoring. In the case where a patient is weaned from infusion, full ICP control will be assumed. | ICP will be recorded continuously and the proportion of time during which ICP is uncontrolled will be calculated. Specifically, this will be measured as any period during which ICP > 20 mmHg for 600 seconds or longer. | 120 hours post initiation of monitoring | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Therapy Intensity Level (TIL), reflecting the amount and duration of therapy required to control ICP. TIL incorporates, among others, variables such as degree of head elevation, level of sedation, volume of CSF drainage, and hypocapnia. |  | Daily | 
| Long-term outcomes measured by Disability Rating Scale and Glasgow Outcome Scale-Extended |  | 3 and 6 months post-injury | 
| Incidence of pre-determined severe adverse events (SAEs): brain hypoxia, delayed decompression, pulmonary edema, renal failure, respiratory complications, seizures, systemic hypoxia, and uncontrollable ICP | For each patient, we will count the number of SAEs in each category. Total SAEs by category and average number of SAEs per patient will be compared between the two study treatments. | Each occurence of an SAE during the patient's hospital stay will be recorded. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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traumatic brain injury, hypertonic saline therapy, intracranial pressure