Hypertonic Saline vs. Mannitol for Elevated Intercranial Pressure

This study has been terminated.

(A significant reduction in head injuries coupled with more frequent use of crainectomy reduced the number of potential subjects.)

Sponsor:

Collaborator:

Department of Defense

Information provided by (Responsible Party):

University of Cincinnati

ClinicalTrials.gov Identifier:

NCT01111682

First received: April 22, 2010

Last updated: March 4, 2013

Last verified: March 2013

History of Changes

Purpose

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	Intervention	Phase
Traumatic Brain Injury Elevated Intracranial Pressure	Drug: Mannitol Drug: Hypertonic Saline	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Hypertonic Saline vs. Mannitol for Elevated Intercranial Pressure

Resource links provided by NLM:

MedlinePlus related topics: Edema Traumatic Brain Injury

Drug Information available for: Mannitol

U.S. FDA Resources

Further study details as provided by University of Cincinnati:

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. [ Time Frame: 120 hours post initiation of monitoring ] [ Designated as safety issue: No ]
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. [ Time Frame: Daily ] [ Designated as safety issue: No ]
Long-term outcomes measured by Disability Rating Scale and Glasgow Outcome Scale-Extended [ Time Frame: 3 and 6 months post-injury ] [ Designated as safety issue: Yes ]
Incidence of pre-determined severe adverse events (SAEs): brain hypoxia, delayed decompression, pulmonary edema, renal failure, respiratory complications, seizures, systemic hypoxia, and uncontrollable ICP [ Time Frame: Each occurence of an SAE during the patient's hospital stay will be recorded. ] [ Designated as safety issue: Yes ]
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.

Enrollment:	5
Study Start Date:	April 2010
Study Completion Date:	November 2010
Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01111682

Locations

United States, Ohio
University Hospital
Cincinnati, Ohio, United States, 45267

Sponsors and Collaborators

University of Cincinnati

Department of Defense

Investigators

Principal Investigator:

Lori Shutter, MD

Department of Neurology College of Medicine University of Cincinnati

More Information

Publications:

Zornow MH. Hypertonic saline as a safe and efficacious treatment of intracranial hypertension. J Neurosurg Anesthesiol. 1996 Apr;8(2):175-7. Review. No abstract available.

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. Review. No abstract available.

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. Review.

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.

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. Review.

Responsible Party:	University of Cincinnati
ClinicalTrials.gov Identifier:	NCT01111682 History of Changes
Other Study ID Numbers:	Shutter-2010-01
Study First Received:	April 22, 2010
Last Updated:	March 4, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Cincinnati:

traumatic brain injury
hypertonic saline therapy
intracranial pressure

Additional relevant MeSH terms:

Intracranial Hypertension
Brain Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries

Mannitol
Diuretics, Osmotic
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 23, 2013

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