Hypertonic Saline vs. Mannitol for Elevated Intercranial Pressure

Traumatic Brain Injury Clinical Trial

Official title:

Hypertonic Saline vs. Mannitol for Elevated Intercranial Pressure

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01111682
• Other study ID #: Shutter-2010-01
• Status: Terminated
• Phase: Phase 3
• First received: April 22, 2010
• Last updated: March 4, 2013
• Start date: April 2010
• Est. completion date: November 2010

Study information

• Verified date: March 2013
• Source: University of Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: November 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Injuries
• Elevated Intracranial Pressure
• Intracranial Hypertension
• Traumatic Brain Injury

Intervention

Drug:
• Mannitol
0.9% normal saline infusion and boluses of mannitol
• Hypertonic Saline
3% hypertonic saline continuous infusion, with intermittent boluses as needed

Locations

Country	Name	City	State
United States	University Hospital	Cincinnati	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
University of Cincinnati	United States Department of Defense

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View 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. — View 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. Review. — View 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. Review. — View Citation

Zornow MH. Hypertonic saline as a safe and efficacious treatment of intracranial hypertension. J Neurosurg Anesthesiol. 1996 Apr;8(2):175-7. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	Long-term outcomes measured by Disability Rating Scale and Glasgow Outcome Scale-Extended		3 and 6 months post-injury	Yes
Secondary	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.	Yes