- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01215019
Osmotic Therapy for Treatment of Intracranial Hypertension for Traumatic Brain Injury
20% Mannitol vs 3% Hypertonic Saline in the Treatment of Intracranial Hypertension in Patients With Traumatic Brain Injury: A Double-blinded, Randomized Trial
Study Overview
Status
Conditions
Intervention / Treatment
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
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Indiana
-
Indianapolis, Indiana, United States, 46202
- Wishard Memorial Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Arm 1
20% Mannitol
|
20% Mannitol, 1-5 doses as needed to control ICP
|
Active Comparator: Arm 2
3% sodium chloride
|
3% sodium chloride injection, 1-5 doses, as needed to control ICP
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Assess efficacy of 20% mannitol versus 3% MaCl in controlling elevated intracranial pressure in acute traumatic brain injury
Time Frame: Two years
|
Two years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Richard B. Rodgers, MD, Indiana University
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Craniocerebral Trauma
- Trauma, Nervous System
- Hypertension
- Brain Injuries
- Wounds and Injuries
- Brain Injuries, Traumatic
- Intracranial Hypertension
- Physiological Effects of Drugs
- Natriuretic Agents
- Diuretics, Osmotic
- Diuretics
- Mannitol
Other Study ID Numbers
- 1004-10
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Traumatic Brain Injury
-
Fondazione per la Ricerca Ospedale MaggioreCompletedBrain Injuries, Traumatic | Brain Injury Traumatic Severe | Brain Injury Traumatic ModerateItaly
-
Toronto Rehabilitation InstituteCentre for Aging and Brain Health Innovation; Ontario Neurotrauma FoundationUnknownBrain Injuries, Traumatic | Brain Injury, Chronic | Brain Injury Traumatic Severe | Brain Injury Traumatic ModerateCanada
-
Hospital Sirio-LibanesUniversity of Sao Paulo; Ministry of Health, Brazil; Hospital Sao Rafael; PROAD... and other collaboratorsRecruitingBrain Injury Traumatic Severe | Brain Injury Traumatic Moderate | Post Traumatic EpilepsyBrazil
-
University of TurkuTurku University Hospital; The Finnish Funding Agency for Technology and Innovation... and other collaboratorsCompletedBrain Injuries | TBI (Traumatic Brain Injury) | Brain Injuries, Traumatic | Traumatic Brain Injury | Injury, Brain, TraumaticFinland
-
Children's Hospital Medical Center, CincinnatiUniversity of CincinnatiCompletedBrain Injury Traumatic MildUnited States
-
BrainScope Company, Inc.RecruitingTBI (Traumatic Brain Injury) | Concussion, Brain | MTBI - Mild Traumatic Brain Injury | Closed Head InjuryUnited States
-
Institut National de la Santé Et de la Recherche...Institut National de Recherche en Informatique et en AutomatiqueNot yet recruitingTBI (Traumatic Brain Injury)France
-
University of Sao Paulo General HospitalUnknownTraumatic Brain Injury | Severe Brain Injury | Closed Traumatic Brain InjuryBrazil
-
Queen Mary University of LondonCompleted
-
First Affiliated Hospital Xi'an Jiaotong UniversityXijing Hospital; Second Affiliated Hospital of Wenzhou Medical University; Central... and other collaboratorsRecruitingMTBI - Mild Traumatic Brain Injury | Moderate Traumatic Brain InjuryChina
Clinical Trials on Mannitol
-
Seoul National University HospitalUnknown
-
PharmaxisCompletedCystic FibrosisUnited Kingdom
-
Shandong UniversityUnknown
-
PharmaxisCompletedCystic FibrosisUnited Kingdom
-
PharmaxisWithdrawnCOPD | ExacerbationAustralia
-
University of British ColumbiaCompleted
-
PharmaxisCompleted
-
Kuopio University HospitalJohn Hunter HospitalRecruiting
-
Abela Pharmaceuticals, Inc.Ohio State University; University of California, Irvine; Dr. Mahajan's Hospital...UnknownSevere Head TraumaUnited States