Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Hypernatremia for the Prevention and Treatment of Cerebral Edema in Traumatic Brain Injury

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2012 by Massachusetts General Hospital.
Recruitment status was  Not yet recruiting
Sponsor:
Information provided by (Responsible Party):
Brian P. Walcott, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01605357
First received: May 22, 2012
Last updated: May 23, 2012
Last verified: May 2012
  Purpose

Cerebral edema is seen heterogenous group of neurological disease states that mainly fall under the categories of metabolic, infectious, neoplasia, cerebrovascular, and traumatic brain injury disease states. Regardless of the driving force, cerebral edema is defined as the accumulation of fluid in the brain's intracellular and extracellular spaces. This occurs secondary to alterations in the complex interplay between four distinct fluid compartments within the cranium. In any human cranium; fluid is contained in the blood, the cerebrospinal fluid, interstitial fluid of the brain parenchyma, and the intracellular fluid of the neurons and glia. Fluid movement occurs normally between these compartments and depends on specific concentrations of solutes (such as sodium) and water. In brain-injured states, the normal regulation of this process is disturbed and cerebral edema can develop. Cerebral edema leads to increased intracranial pressure and mortality secondary to brain tissue compression, given the confines of the fixed-volume cranium. Additionally, secondary neuronal dysfunction or death can occur at the cellular level secondary to the disruption of ion gradients that control metabolism and function.

While studies utilizing bolus dosing of hyperosmolar therapy to target signs or symptoms of increased intracranial pressure secondary to cerebral edema are numerous, there is a paucity of studies relating to continuous infusion of hyperosmolar therapy for targeted sustained hypernatremia for the prevention and treatment of cerebral edema. The investigators hypothesize that induced, sustained hypernatremia following traumatic brain injury will decrease the rate of cerebral edema formation and improve patient outcomes.


Condition Intervention Phase
Traumatic Brain Injury
Subdural Hematoma
Cerebral Contusion
Head Injury
Cerebral Edema
Drug: Induced, sustained hypernatremia using hypertonic saline
Drug: Standard of care (hypertonic saline and mannitol; serum sodium)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open Label Clinical Trial of Sustained Hypernatremia for the Prevention and Treatment of Cerebral Edema in Traumatic Brain Injury

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Primary Efficacy Objective [ Time Frame: 72 hours ; 120 hours ; 30 days ] [ Designated as safety issue: No ]
    The primary efficacy objective of this study is to assess whether patients with severe TBI treated with sustained hypernatremia will show a decrease in neuroimaging defined edema compared to patients treated as the current standard of care.

  • Primary Safety Objective [ Time Frame: Through 30 days ] [ Designated as safety issue: Yes ]
    The primary safety objective is to assess the safety and tolerability of sustained hypernatremia compared to the goal of avoiding hyponatremia in patients with severe traumatic brain injury. Safety will be assessed by a review of the incidence of mortality and adverse events, as well as by analysis of relevant laboratory data.


Secondary Outcome Measures:
  • Short term neurological outcome [ Time Frame: 30 days ] [ Designated as safety issue: No ]

    The secondary outcome measure of this study will be assess whether patients with TBI treated with sustained hypernatremia will benefit patients in terms of short term neurological outcome - defined as need for tracheostomy during principal admission.

    Other secondary outcome measures will be need for delayed craniectomy and cumulative dosage of bolus dosing hyperosmolar therapy.



Estimated Enrollment: 40
Study Start Date: July 2012
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Standard Care
Patients will be managed to maintain a goal serum sodium of > 135 mmol/L , a well recognized value in the management of severe traumatic brain injury.
Drug: Standard of care (hypertonic saline and mannitol; serum sodium)
Bolus dosing of hypertonic saline and mannitol are to be administered at the discretion of the provider to treat elevated intracranial pressure based on practice guidelines. Hyponatremia ( serum sodium < 135 mmol/L) is to be corrected at the discretion of the provider.
Experimental: Induced Hypernatremia
Patients will be treated with induced, sustained hypernatremia for 5 days following injury by using hypertonic saline to target a goal serum sodium of 150-160 mmol/L
Drug: Induced, sustained hypernatremia using hypertonic saline

Patients in the experimental arm will receive hypertonic saline to target a serum sodium goal of 150 - 160 mmol/L. All hypertonic saline will be administered intravenously.

Loading phase: Upon enrollment 23.4 % hypertonic saline (volume 20 cc) will be administered via a central venous catheter. A continuous infusion of 3% hypertonic saline will be administered at a rate of 30 cc per hour and titrated every six hours to target a serum sodium goal of 150-160 mmol/L.

Maintenance phase: Titrate serum sodium to 150-160 mmol/L using continuous 3% hypertonic saline infusion.

Discontinuation phase: After 5 days of completed therapy, begin to wean 3% hypertonic saline rate by 10cc every 6 hours. Discontinue hypertonic saline infusion after infusing at a rate of 20cc an hour for 6 hours.

Bolus dosing of hypertonic saline and mannitol are to be administered at the discretion of the provider to treat elevated intracranial pressure based on practice guidelines


  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults (18 - 60 years old)
  • Severe traumatic brain injury with intracranial pressure monitoring
  • Initial GCS 5-8 (obtained free of the effects of neuromuscular blockade or sedatives)
  • Clearly defined time of injury no more than 8 hours before administration of study drug
  • Written consent obtained from legally authorized representative (LAR)
  • Severe swelling prone injury patterns:

    1. Contusion - frontal or temporal (> 20 cc)
    2. Acute convexity subdural hematoma with any evidence of midline shift

Exclusion Criteria:

  • Patients undergoing emergent (within 15 minutes) or urgent neurosurgery (within 4 hours) following emergency department arrival (bedside procedures, such as intracranial pressure monitor placement are excluded)
  • Posterior fossa lesions
  • Penetrating brain injury
  • Spinal column instability and/or spinal cord injury with neurological deficit
  • Pregnant
  • Concomitant severe nonsurvivable injury
  • Acute renal failure ; Chronic renal failure (serum creatinine of > 2.5 mg/dL, history of ongoing dialysis, glomerular filtration rate <30mL/min/1.73 m2); Severe pulmonary edema; Severe heart failure; Severe liver failure (AST, ALT, or bilirubin > 2 times normal)
  • Known use of warfarin, clopidogrel, prasugrel, cilostazol, heparin, low molecular weight heparin, heparinoids, abciximab or similar antiplatelet agents
  • Treatment with another investigational drug within the prior 30 days
  • Systolic blood pressure < 90 mm HG not responsive to fluid resuscitation
  • INR > 1.4
  • Hospitalization for brain injury or neurological disease within previous 3 years
  • Admission serum sodium < 135 mmol/L
  • > 8 hours from the time of injury to admission
  • Fix/dilated pupil suspected to be secondary to brainstem compression
  • Duret (brainstem) hemorrhage indicating brainstem herniation
  • PaO2 < 60 mmHg on admission (when blood gases are drawn as standard of care)
  • Prisoner or other persons unable to make a true, voluntary and uncoerced decision whether or not to participate in the study
  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: NCT01605357

Contacts
Contact: Brian V Nahed, MD 617-726-1002 bnahed@partners.org

Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Study Chair: Brian P Walcott, MD Massachusetts General Hospital
Principal Investigator: Brian V Nahed, MD Massachusetts General Hospital
Study Director: Sameer A Sheth, MD PhD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Brian P. Walcott, Surgeon - Department of Neurosurgery, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01605357     History of Changes
Other Study ID Numbers: MGH-HH5
Study First Received: May 22, 2012
Last Updated: May 23, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Brain Injuries
Hematoma, subdural
Decompressive Craniectomy
Saline solution, hypertonic
Hypernatremia
Intracranial hemorrhages
Head Injuries, closed
Intracranial pressure
Brain edema
Critical care
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Wounds and Injuries
Physiological Effects of Drugs
Pharmacologic Actions

Additional relevant MeSH terms:
Brain Edema
Brain Injuries
Craniocerebral Trauma
Edema
Hematoma
Hematoma, Subdural
Hypernatremia
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Hemorrhage
Intracranial Hemorrhage, Traumatic
Intracranial Hemorrhages
Metabolic Diseases
Nervous System Diseases
Pathologic Processes
Signs and Symptoms
Trauma, Nervous System
Vascular Diseases
Water-Electrolyte Imbalance
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 27, 2014