Osmotic Therapy for Treatment of Intracranial Hypertension for Traumatic Brain Injury

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01215019
Recruitment Status : Withdrawn (Lack of funding; not subjects enrolled)
First Posted : October 5, 2010
Last Update Posted : April 4, 2013
Information provided by (Responsible Party):
Indiana University

Brief Summary:
Osmotic therapy is a mainstay in the treatment of intracranial hypertension after traumatic brain injury.This study proposes to compare two hypertonic saline agents in patients with traumatic brain injury.

Condition or disease Intervention/treatment Phase
Traumatic Brain Injury Drug: Mannitol Drug: NaCl Not Applicable

Detailed Description:

Osmotic therapy is a mainstay in the treatment of intracranial hypertension after traumatic brain injury. Despite sparse concrete evidence of beneficial effects on patient outcome, it has been widely accepted by treating physicians that osmotic therapy is effective, at least in helping control elevated intracranial pressure (ICP), and control of ICP has been shown to improve outcome. Mannitol is the most commonly utilized agent. It is widely available, effective, and has a low side-effect profile. Large doses for long term periods have been shown to be safe, but its usefulness is limited by elevation of serum osmolarity and potential alteration in renal function, and its efficacy seems to diminish with repeated doses. Rebound intracranial hypertension has been reported after discontinuation of large doses. Other hypertonic agents such as urea and glycerol are no longer used.

More recently, hypertonic saline (HTS) solutions of various concentrations have become available, and have been shown in several animal research studies and small human trials to be safe and effective in the management of intracranial hypertension. HTS does not cross the blood-brain barrier, and has the ability to improve intravascular volume without the osmotic diuresis effect of mannitol. Several institutions routinely use HTS solutions in the management of traumatic brain injuries, and the use of both mannitol and HTS is common. Additionally longer-term use of HTS is not as restricted by plasma osmolarity. There have been several small trials comparing the two agents, but these studies have been relatively poorly controlled and therefore reached limited conclusions. At our institution both agents (in the forms of 20% mannitol and 3% sodium chloride) are used routinely, with no particular rationale for one over the other. There is suggestion that one agent may be better than the other, but this has not been explicitly tested in humans.

It is our hypothesis that HTS and mannitol both adequately treat intracranial hypertension, but that HTS may have additional benefits of allowing more frequent and/or longer-term dosing, and volume expansion without osmotic diuresis (thereby improving the patient's overall fluid state, potentially decreasing morbidity).

We propose a study of patients with acute traumatic brain injury requiring osmotic therapy to control elevated ICP, comparing the use of 20% mannitol to 3% sodium chloride (NaCl).

Specific Aims:

Primary Goal:

Assess efficacy of 20% mannitol versus 3% NaCl in controlling elevated ICP in acute traumatic brain injury

Secondary Goals:

Assess effects on hemodynamic parameters (mean arterial pressure, cerebral perfusion pressure, central venous pressure and volume status) Assess effects on serum sodium and osmolarity Assess effects on patient outcomes at discharge

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: 20% Mannitol vs 3% Hypertonic Saline in the Treatment of Intracranial Hypertension in Patients With Traumatic Brain Injury: A Double-blinded, Randomized Trial
Study Start Date : October 2010
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Arm 1
20% Mannitol
Drug: Mannitol
20% Mannitol, 1-5 doses as needed to control ICP

Active Comparator: Arm 2
3% sodium chloride
Drug: NaCl
3% sodium chloride injection, 1-5 doses, as needed to control ICP
Other Name: 3% sodium chloride injection

Primary Outcome Measures :
  1. Assess efficacy of 20% mannitol versus 3% MaCl in controlling elevated intracranial pressure in acute traumatic brain injury [ Time Frame: Two years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • All hemodynamically stable patients aged 18-65 presenting with acute traumatic brain injury requiring monitoring of intracranial pressure (ICP) will be screened for randomization.

Exclusion Criteria:

  • Patients with known pre-existing renal abnormalities or serum creatinine greater than or equal to 2.0mg/dl will be excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01215019

United States, Indiana
Wishard Memorial Hospital
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Indiana University
Principal Investigator: Richard B. Rodgers, MD Indiana University

Responsible Party: Indiana University Identifier: NCT01215019     History of Changes
Other Study ID Numbers: 1004-10
First Posted: October 5, 2010    Key Record Dates
Last Update Posted: April 4, 2013
Last Verified: April 2013

Keywords provided by Indiana University:
traumatic brain injury

Additional relevant MeSH terms:
Wounds and Injuries
Brain Injuries
Brain Injuries, Traumatic
Intracranial Hypertension
Vascular Diseases
Cardiovascular Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Diuretics, Osmotic
Natriuretic Agents
Physiological Effects of Drugs