Hypertonic Saline vs. Mannitol for Elevated Intercranial Pressure

Phase 3

Terminated

• Conditions: Traumatic Brain Injury; Elevated Intracranial Pressure
• Interventions: Drug: Mannitol; Drug: Hypertonic Saline

• Registration Number: NCT01111682
• Lead Sponsor: University of Cincinnati

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.

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 Timeline

• Study Start: 2010-04
• Study First Submitted: 2010-04-22
• Study First Submitted QC: 2010-04-26
• Study First Posted: 2010-04-27
• Primary Completion: 2010-11
• Study Completion: 2010-11
• Status Verified: 2013-03
• Last Update Submitted: 2013-03-04
• Last Update Posted: 2013-03-05

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 5

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Mannitol	Mannitol	0.9% normal saline infusion and boluses of mannitol
Hypertonic Saline	Hypertonic Saline	3% hypertonic saline continuous infusion, with intermittent boluses as needed

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.

Trial Locations

Locations (1)

University Hospital; 🇺🇸 Cincinnati, Ohio, United States