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Hypertonic Saline vs. Mannitol for Elevated Intercranial Pressure

Primary Purpose

Traumatic Brain Injury, Elevated Intracranial Pressure

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Mannitol
Hypertonic Saline
Sponsored by
University of Cincinnati
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Traumatic Brain Injury focused on measuring traumatic brain injury, hypertonic saline therapy, intracranial pressure

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Mannitol

Hypertonic Saline

Arm Description

0.9% normal saline infusion and boluses of mannitol

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

Outcomes

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.
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.
Long-term outcomes measured by Disability Rating Scale and Glasgow Outcome Scale-Extended
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.

Full Information

First Posted
April 22, 2010
Last Updated
March 4, 2013
Sponsor
University of Cincinnati
Collaborators
United States Department of Defense
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1. Study Identification

Unique Protocol Identification Number
NCT01111682
Brief Title
Hypertonic Saline vs. Mannitol for Elevated Intercranial Pressure
Official Title
Hypertonic Saline vs. Mannitol for Elevated Intercranial Pressure
Study Type
Interventional

2. Study Status

Record Verification Date
March 2013
Overall Recruitment Status
Terminated
Why Stopped
A significant reduction in head injuries coupled with more frequent use of crainectomy reduced the number of potential subjects.
Study Start Date
April 2010 (undefined)
Primary Completion Date
November 2010 (Actual)
Study Completion Date
November 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Cincinnati
Collaborators
United States Department of Defense

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Traumatic Brain Injury, Elevated Intracranial Pressure
Keywords
traumatic brain injury, hypertonic saline therapy, intracranial pressure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Mannitol
Arm Type
Active Comparator
Arm Description
0.9% normal saline infusion and boluses of mannitol
Arm Title
Hypertonic Saline
Arm Type
Active Comparator
Arm Description
3% hypertonic saline continuous infusion, with intermittent boluses as needed
Intervention Type
Drug
Intervention Name(s)
Mannitol
Intervention Description
0.9% normal saline infusion and boluses of mannitol
Intervention Type
Drug
Intervention Name(s)
Hypertonic Saline
Intervention Description
3% hypertonic saline continuous infusion, with intermittent boluses as needed
Primary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
120 hours post initiation of monitoring
Secondary Outcome Measure Information:
Title
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.
Time Frame
Daily
Title
Long-term outcomes measured by Disability Rating Scale and Glasgow Outcome Scale-Extended
Time Frame
3 and 6 months post-injury
Title
Incidence of pre-determined severe adverse events (SAEs): brain hypoxia, delayed decompression, pulmonary edema, renal failure, respiratory complications, seizures, systemic hypoxia, and uncontrollable ICP
Description
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.
Time Frame
Each occurence of an SAE during the patient's hospital stay will be recorded.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lori Shutter, MD
Organizational Affiliation
Department of Neurology College of Medicine University of Cincinnati
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
8829566
Citation
Zornow MH. Hypertonic saline as a safe and efficacious treatment of intracranial hypertension. J Neurosurg Anesthesiol. 1996 Apr;8(2):175-7. doi: 10.1097/00008506-199604000-00021. No abstract available.
Results Reference
background
PubMed Identifier
11242309
Citation
Doyle JA, Davis DP, Hoyt DB. The use of hypertonic saline in the treatment of traumatic brain injury. J Trauma. 2001 Feb;50(2):367-83. doi: 10.1097/00005373-200102000-00030. No abstract available.
Results Reference
background
PubMed Identifier
11008996
Citation
Qureshi AI, Suarez JI. Use of hypertonic saline solutions in treatment of cerebral edema and intracranial hypertension. Crit Care Med. 2000 Sep;28(9):3301-13. doi: 10.1097/00003246-200009000-00032.
Results Reference
background
PubMed Identifier
2451302
Citation
Gunnar W, Jonasson O, Merlotti G, Stone J, Barrett J. Head injury and hemorrhagic shock: studies of the blood brain barrier and intracranial pressure after resuscitation with normal saline solution, 3% saline solution, and dextran-40. Surgery. 1988 Apr;103(4):398-407.
Results Reference
background
PubMed Identifier
16094147
Citation
Ogden AT, Mayer SA, Connolly ES Jr. Hyperosmolar agents in neurosurgical practice: the evolving role of hypertonic saline. Neurosurgery. 2005 Aug;57(2):207-15; discussion 207-15. doi: 10.1227/01.neu.0000166533.79031.d8.
Results Reference
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Hypertonic Saline vs. Mannitol for Elevated Intercranial Pressure

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