Hypertonic Saline vs. Mannitol for Elevated Intercranial Pressure

Sponsor

University of Cincinnati (Other)

Overall Status

Terminated

CT.gov ID

NCT01111682

Collaborator

United States Department of Defense (U.S. Fed)

Enrollment

Location

Arms

Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Traumatic Brain Injury Elevated Intracranial Pressure	Drug: Mannitol Drug: Hypertonic Saline	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

5 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Hypertonic Saline vs. Mannitol for Elevated Intercranial Pressure

Study Start Date :

Apr 1, 2010

Actual Primary Completion Date :

Nov 1, 2010

Actual Study Completion Date :

Nov 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Mannitol 0.9% normal saline infusion and boluses of mannitol	Drug: Mannitol 0.9% normal saline infusion and boluses of mannitol
Active Comparator: Hypertonic Saline 3% hypertonic saline continuous infusion, with intermittent boluses as needed	Drug: Hypertonic Saline 3% hypertonic saline continuous infusion, with intermittent boluses as needed

Arm

Intervention/Treatment

Active Comparator: Mannitol

0.9% normal saline infusion and boluses of mannitol

Drug: Mannitol

0.9% normal saline infusion and boluses of mannitol

Active Comparator: Hypertonic Saline

3% hypertonic saline continuous infusion, with intermittent boluses as needed

Drug: Hypertonic Saline

3% hypertonic saline continuous infusion, with intermittent boluses as needed

Outcome Measures

Primary Outcome Measures

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. [120 hours post initiation of monitoring]
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.

Secondary Outcome Measures

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 [Each occurence of an SAE during the patient's hospital stay will be recorded.]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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