Traumatic Brain InjuryPhase 1/2NCT01605357
Hypernatremia for the Prevention and Treatment of Cerebral Edema in Traumatic Brain Injury
A Phase 1/2 study testing Induced, sustained hypernatremia using hypertonic saline in people with Traumatic Brain Injury and Subdural Hematoma, run by Massachusetts General Hospital.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Traumatic Brain Injury, Subdural Hematoma, Cerebral Contusion
- What is being tested?
- Induced, sustained hypernatremia using hypertonic saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jul 2012to Aug 2013
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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:
- Contusion - frontal or temporal (> 20 cc)
- Acute convexity subdural hematoma with any evidence of midline shift
Who cannot join
- 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
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- 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
About this study
Official title: A Randomized, Open Label Clinical Trial of Sustained Hypernatremia for the Prevention and Treatment of Cerebral Edema in Traumatic Brain Injury
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.
- Conditions
- Traumatic Brain Injury, Subdural Hematoma, Cerebral Contusion, Head Injury, Cerebral Edema
- Being tested
- Induced, sustained hypernatremia using hypertonic saline, Standard of care (hypertonic saline and mannitol; serum sodium)
- Keywords
- 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
- Medical subject headings
- Brain Injuries, Traumatic, Hematoma, Subdural, Brain Contusion, Craniocerebral Trauma, Brain Edema, Brain Injuries, Hypernatremia, Intracranial Hemorrhages
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Induced, sustained hypernatremia using hypertonic salineDrug
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
Standard of care (hypertonic saline and mannitol; serum sodium)Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Standard Care | Active comparator | 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. Receives: Drug: Standard of care (hypertonic saline and mannitol; serum sodium) |
| Induced Hypernatremia | Experimental | 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 Receives: Drug: Induced, sustained hypernatremia using hypertonic saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Efficacy Objective
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.
Measured: 72 hours ; 120 hours ; 30 days
Primary Safety Objective
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.
Measured: Through 30 days
Secondary outcomes (1)
Short term neurological outcome
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.
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2012 (estimated)
- Study startJul 2012
- Primary completionJul 2013 (estimated)
- Study completionAug 2013 (estimated)
Why it stopped: Never started.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Brian P. Walcott, Massachusetts General Hospital
- Investigators
- Brian P Walcott, MD, Study chair, Massachusetts General HospitalBrian V Nahed, MD, Principal investigator, Massachusetts General HospitalSameer A Sheth, MD PhD, Study director, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01605357
- Sponsor's protocol ID
- MGH-HH5
- Status last verified
- Dec 2016
- First submitted
- 22 May 2012
- Last updated
- 12 Dec 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open Label Clinical Trial of Sustained Hypernatremia for the Prevention and Treatment of Cerebral Edema in Traumatic Brain Injury
- ClinicalTrials.gov ID
- NCT01605357
- Acronym / sponsor ID
- MGH-HH5
- Conditions
- Traumatic Brain Injury, Subdural Hematoma, Cerebral Contusion, Head Injury, Cerebral Edema
- Keywords
- Brain Injuries, Hematoma, subdural, Decompressive Craniectomy, Saline solution, hypertonic, Hypernatremia, Intracranial hemorrhages, Head Injuries, closed, Intracranial pressure
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Never started.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Jul 2012
- Primary completion
- Jul 2013 (estimated)
- Study completion
- Aug 2013 (estimated)
- First posted
- 24 May 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard Care | Active comparator | Drug: Standard of care (hypertonic saline and mannitol; serum sodium)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. |
| Induced Hypernatremia | Experimental | Drug: Induced, sustained hypernatremia using hypertonic salinePatients 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 |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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)
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Induced, sustained hypernatremia using hypertonic salinePatients 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 | Drug | Induced Hypernatremia |
| 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. | Drug | Standard Care |
Primary outcome
Primary Efficacy Objective
Time frame: 72 hours ; 120 hours ; 30 days
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
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.
1 secondary outcome
Short term neurological outcome
Time frame: 30 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brian P Walcott, MD study chair
Massachusetts General Hospital
Brian V Nahed, MD principal investigator
Massachusetts General Hospital
Sameer A Sheth, MD PhD study director
Massachusetts General Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Induced, sustained hypernatremia using hypertonic saline in people with Traumatic Brain Injury and Subdural Hematoma, run by Massachusetts General Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 12 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Efficacy Objective (time frame: 72 hours ; 120 hours ; 30 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2016.