Osmotic Therapy for Treatment of Intracranial Hypertension for Traumatic Brain Injury

Traumatic Brain Injury Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01215019
• Other study ID #: 1004-10
• Status: Withdrawn
• Phase: N/A
• First received: October 4, 2010
• Last updated: April 1, 2013
• Start date: October 2010
• Est. completion date: October 2020

Study information

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

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: October 2020
• Est. primary completion date: October 2020
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Injuries
• Intracranial Hypertension
• Traumatic Brain Injury

Intervention

Drug:
• Mannitol
20% Mannitol, 1-5 doses as needed to control ICP
• NaCl
3% sodium chloride injection, 1-5 doses, as needed to control ICP

Locations

Country	Name	City	State
United States	Wishard Memorial Hospital	Indianapolis	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Indiana University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assess efficacy of 20% mannitol versus 3% MaCl in controlling elevated intracranial pressure in acute traumatic brain injury		Two years	No