Hypertonic Saline vs. Mannitol for Elevated Intercranial Pressure

NCT01111682 | Terminated Phase 3

• 1 other identifier: Shutter-2010-01
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Traumatic Brain Injury; Elevated Intracranial Pressure

Keywords

traumatic brain injury; hypertonic saline therapy; intracranial pressure

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (3)

• 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.

Study Arms (2)

Mannitol

ACTIVE COMPARATOR

0.9% normal saline infusion and boluses of mannitol

Drug: Mannitol

Hypertonic Saline

ACTIVE COMPARATOR

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

Drug: Hypertonic Saline

Interventions

Mannitol DRUG

0.9% normal saline infusion and boluses of mannitol

Mannitol

Hypertonic Saline DRUG

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

Hypertonic Saline

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Cincinnati: lead
• United States Department of Defense: collaborator

Study Sites (1)

University Hospital

Cincinnati, Ohio, 45267, United States

Location

Related Publications (5)

• 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.

  PMID: 8829566 BACKGROUND

• 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.

  PMID: 11242309 BACKGROUND

• 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.

  PMID: 11008996 BACKGROUND

• 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.

  PMID: 2451302 BACKGROUND

• 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.

  PMID: 16094147 BACKGROUND

MeSH Terms

Conditions

Brain Injuries, Traumatic; Intracranial Hypertension

Interventions

Mannitol; Saline Solution, Hypertonic

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates; Hypertonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Lori Shutter, MD

  Department of Neurology College of Medicine University of Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2010
• First Posted: April 27, 2010
• Study Start: April 1, 2010
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: March 5, 2013

Record last verified: 2013-03

Locations

US (1)