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Hypertonic Saline vs. Mannitol for Elevated Intercranial Pressure

This study has been terminated.
(A significant reduction in head injuries coupled with more frequent use of crainectomy reduced the number of potential subjects.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Cincinnati
ClinicalTrials.gov Identifier:
NCT01111682
First received: April 22, 2010
Last updated: March 4, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Traumatic Brain Injury
Elevated Intracranial Pressure
Drug: Mannitol
Drug: Hypertonic Saline
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Hypertonic Saline vs. Mannitol for Elevated Intercranial Pressure

Resource links provided by NLM:


Further study details as provided by University of Cincinnati:

Primary Outcome Measures:
  • 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. [ Time Frame: 120 hours post initiation of monitoring ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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. [ Time Frame: Daily ] [ Designated as safety issue: No ]
  • Long-term outcomes measured by Disability Rating Scale and Glasgow Outcome Scale-Extended [ Time Frame: 3 and 6 months post-injury ] [ Designated as safety issue: Yes ]
  • Incidence of pre-determined severe adverse events (SAEs): brain hypoxia, delayed decompression, pulmonary edema, renal failure, respiratory complications, seizures, systemic hypoxia, and uncontrollable ICP [ Time Frame: Each occurence of an SAE during the patient's hospital stay will be recorded. ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 5
Study Start Date: April 2010
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Mannitol
0.9% normal saline infusion and boluses of mannitol
Drug: Mannitol
0.9% normal saline infusion and boluses of mannitol
Active Comparator: Hypertonic Saline
3% hypertonic saline continuous infusion, with intermittent boluses as needed
Drug: Hypertonic Saline
3% hypertonic saline continuous infusion, with intermittent boluses as needed

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01111682

Locations
United States, Ohio
University Hospital
Cincinnati, Ohio, United States, 45267
Sponsors and Collaborators
University of Cincinnati
Investigators
Principal Investigator: Lori Shutter, MD Department of Neurology College of Medicine University of Cincinnati
  More Information

Publications:
Responsible Party: University of Cincinnati
ClinicalTrials.gov Identifier: NCT01111682     History of Changes
Other Study ID Numbers: Shutter-2010-01
Study First Received: April 22, 2010
Last Updated: March 4, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Cincinnati:
traumatic brain injury
hypertonic saline therapy
intracranial pressure

Additional relevant MeSH terms:
Brain Injuries
Brain Diseases
Intracranial Hypertension
Central Nervous System Diseases
Craniocerebral Trauma
Nervous System Diseases
Trauma, Nervous System
Wounds and Injuries
Mannitol
Cardiovascular Agents
Diuretics
Diuretics, Osmotic
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014