Elevated Intracranial PressureNCT01108744
Double Blind Study of Hypertonic Saline vs Mannitol in the Management of Increased Intracranial Pressure (ICP).
A study testing hypertonic saline and Mannitol in people with Elevated Intracranial Pressure, run by Beth Israel Deaconess Medical Center at 1 site in United States.
Trial summary
The study goal is to compare the management of increased intra-cranial pressure (ICP) using 3% hypertonic saline vs. mannitol (given in same osmolar loads). Primary hypothesis: 1. Hypertonic saline will be non-inferior to mannitol in decreasing elevated ICP. Secondary hypotheses: 1. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Elevated Intracranial Pressure
- What is being tested?
- hypertonic saline and Mannitol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2012to Jan 2014
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- elevated ICP requiring ICP monitoring
- ICP ≥ 25 mmHg 5 min after ICP bolt or EVD placement
Who cannot join
- Requiring decompressive craniotomy or post decompressive craniotomy
- Hyponatremia (sodium level < 125 mEq/L)
- Hypernatremia (sodium > 155 mmol/L)
- Serum osmolality ≤ 250 mOsm/kg
- Serum osmolality ≥ 320 mOsm/kg
- Physical exam compatible with brain death
- Patients on hemodialysis with end-stage renal disease
Trial locations and contacts
1 site in 1 country.
United States1 site
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
About this study
The study goal is to compare the management of increased intra-cranial pressure (ICP) using 3% hypertonic saline vs. mannitol (given in same osmolar loads).
Primary hypothesis:
- Hypertonic saline will be non-inferior to mannitol in decreasing elevated ICP.
Secondary hypotheses:
- Hypertonic saline therapy will result with fewer complications than mannitol
- ICP reduction duration will be longer using hypertonic saline when compared with mannitol
Read the detailed description
There is growing evidence in the literature indicating that ICP and Cerebral Perfusion Pressure measurements may not be sufficient in the management of elevated ICP. Based on this evidence, monitoring of partial brain tissue oxygenation has gain acceptance among neurosurgeons and neurointensivists, and has become a standard of care monitor in some centers across the country. There is, however, insufficient information in the literature describing the effects of hyperosmolar medications on regional brain tissue oxygenation.
We intend to undertake this non-inferiority, prospective, randomized double-blind study to answer very important clinical questions not yet answered in the literature: Will hypertonic saline therapy, given at equiosmolar load, be non-inferior to mannitol in reducing elevated ICP?
- Conditions
- Elevated Intracranial Pressure
- Being tested
- hypertonic saline, Mannitol
- Keywords
- clinical trial, mannitol, intracranial pressure (ICP), hypertonic saline, cerebral edema, traumatic brain injury (TBI)
- Medical subject headings
- Intracranial Hypertension, Brain Edema, Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hypertonic salineDrug
3% hypertonic saline, dosed by ideal patient weight
MannitolDrug
Also called Osmitrol
Mannitol 20% intravenous solution, dosed by patient's ideal body weight
| Study group | Role | What they receive |
|---|---|---|
| hypertonic saline | Active comparator | 3% hypertonic saline, dosed by ideal patient weight Receives: Drug: hypertonic saline |
| Mannitol | Active comparator | 20% mannitol, dosed by patient's ideal body weight Receives: Drug: Mannitol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent reduction of ICP from baseline
Measured: 30 minutes from completion of medication administration
Secondary outcomes (12)
Time from study drug administration completion to ICP < 25 mmHg
Measured: First 72 hours
Cumulative duration of ICP below 25 mmHg
Measured: First 24 hours
Cumulative duration of ICP below 25 mmHg
Measured: First 72 hours
Cumulative duration of cerebral perfusion pressure (CPP) above 60 mmHg
Measured: First 24 hours
Cumulative duration of cerebral perfusion pressure (CPP) above 60 mmHg
Measured: First 72 hours
Cumulative duration of regional oxygen partial pressure (pbtO2) > 20%
Measured: two hours following each dose administration during the first 24 hours
Total dose of medications given
Measured: First 24 hours; also over 3 days
Frequency of treatment failure
Treatment failure defined as ICP > 30 mmHg for > 30 minutes
Measured: First 72 hours
Frequency of rebound intracranial hypertension
Rebound intracranial hypertension defined as ICP > 25 mmHg for more than 10 minutes following ICP stabilization
Measured: First 72 hours
Frequency of composite Major Adverse Events
- acute kidney injury as defined by an increase in creatinine x 2 or GFR decrease > 50% or urine output < 0.5 ml/kg/h for 12 hours, compared to baseline, as per RIFLE criteria
- hypotensive episodes (SBP < 90 mmHg for more than 10 minutes)
- hemodynamic instability as measured by decrease of cardiac output by more than 15% within two hours following medication administration
- pulmonary edema as defined by ELWI I> 10
Measured: 3 days
Difference in inflammatory response
Determined by analysis of cytokine and inflammatory biomarkers.
Measured: Regular intervals over first 3 days
Difference in average pre-discharge stroke scale score
Measured: hospital discharge (or 30 days if not discharged)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2010 (estimated)
- Study startJan 2012
- Primary completionJan 2014 (estimated)
- Study completionJan 2014 (estimated)
Why it stopped: Timeline to consent prior to intervention start was unfeasible.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Elevated Intracranial PressureStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beth Israel Deaconess Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Achikam Orin-Grinberg, Beth Israel Deaconess Medical Center
- Investigators
- Achikam Oren-Grinberg, MD, Principal investigator, Beth Israel Deaconess Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01108744
- Sponsor's protocol ID
- 2009P000313
- Status last verified
- Mar 2017
- First submitted
- 16 Apr 2010
- Last updated
- 16 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Shackford SR, Bourguignon PR, Wald SL, Rogers FB, Osler TM, Clark DE. Hypertonic saline resuscitation of patients with head injury: a prospective, randomized clinical trial. J Trauma. 1998 Jan;44(1):50-8. doi: 10.1097/00005373-199801000-00004.
PubMed 9464749BARRY KG, BERMAN AR. Mannitol infusion. III. The acute effect of the intravenous infusion of mannitol on blood and plasma volumes. N Engl J Med. 1961 May 25;264:1085-8. doi: 10.1056/NEJM196105252642105. No abstract available.
PubMed 13687351Brain Trauma Foundation; American Association of Neurological Surgeons; Congress of Neurological Surgeons; Joint Section on Neurotrauma and Critical Care, AANS/CNS; Bratton SL, Chestnut RM, Ghajar J, McConnell Hammond FF, Harris OA, Hartl R, Manley GT, Nemecek A, Newell DW, Rosenthal G, Schouten J, Shutter L, Timmons SD, Ullman JS, Videtta W, Wilberger JE, Wright DW. Guidelines for the management of severe traumatic brain injury. II. Hyperosmolar therapy. J Neurotrauma. 2007;24 Suppl 1:S14-20. doi: 10.1089/neu.2007.9994. No abstract available.
PubMed 17511539The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on Neurotrauma and Critical Care. Use of mannitol. J Neurotrauma. 2000 Jun-Jul;17(6-7):521-5. doi: 10.1089/neu.2000.17.521.
PubMed 10937895Bereczki D, Liu M, Prado GF, Fekete I. Cochrane report: A systematic review of mannitol therapy for acute ischemic stroke and cerebral parenchymal hemorrhage. Stroke. 2000 Nov;31(11):2719-22. doi: 10.1161/01.str.31.11.2719.
PubMed 11062300Qureshi AI, Suarez JI, Bhardwaj A, Mirski M, Schnitzer MS, Hanley DF, Ulatowski JA. Use of hypertonic (3%) saline/acetate infusion in the treatment of cerebral edema: Effect on intracranial pressure and lateral displacement of the brain. Crit Care Med. 1998 Mar;26(3):440-6. doi: 10.1097/00003246-199803000-00011.
PubMed 9504569Huang SJ, Chang L, Han YY, Lee YC, Tu YK. Efficacy and safety of hypertonic saline solutions in the treatment of severe head injury. Surg Neurol. 2006 Jun;65(6):539-46; discussion 546. doi: 10.1016/j.surneu.2005.11.019.
PubMed 16720165
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double Blind Study of Hypertonic Saline vs Mannitol in the Management of Increased Intracranial Pressure (ICP).
- ClinicalTrials.gov ID
- NCT01108744
- Acronym / sponsor ID
- 2009P000313
- Conditions
- Elevated Intracranial Pressure
- Keywords
- clinical trial, mannitol, intracranial pressure (ICP), hypertonic saline, cerebral edema, traumatic brain injury (TBI)
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Timeline to consent prior to intervention start was unfeasible.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Beth Israel Deaconess Medical CenterUniversity, hospital or other
- Study start
- Jan 2012
- Primary completion
- Jan 2014 (estimated)
- Study completion
- Jan 2014 (estimated)
- First posted
- 22 Apr 2010 (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.
The study goal is to compare the management of increased intra-cranial pressure (ICP) using 3% hypertonic saline vs. mannitol (given in same osmolar loads).
Primary hypothesis:
- Hypertonic saline will be non-inferior to mannitol in decreasing elevated ICP.
Secondary hypotheses:
- Hypertonic saline therapy will result with fewer complications than mannitol
- ICP reduction duration will be longer using hypertonic saline when compared with mannitol
Detailed description
There is growing evidence in the literature indicating that ICP and Cerebral Perfusion Pressure measurements may not be sufficient in the management of elevated ICP. Based on this evidence, monitoring of partial brain tissue oxygenation has gain acceptance among neurosurgeons and neurointensivists, and has become a standard of care monitor in some centers across the country. There is, however, insufficient information in the literature describing the effects of hyperosmolar medications on regional brain tissue oxygenation.
We intend to undertake this non-inferiority, prospective, randomized double-blind study to answer very important clinical questions not yet answered in the literature: Will hypertonic saline therapy, given at equiosmolar load, be non-inferior to mannitol in reducing elevated ICP?
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| hypertonic saline | Active comparator | Drug: hypertonic saline3% hypertonic saline, dosed by ideal patient weight |
| Mannitol | Active comparator | Drug: Mannitol20% mannitol, dosed by patient's ideal body weight |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age ≥ 18 years
- elevated ICP requiring ICP monitoring
- ICP ≥ 25 mmHg 5 min after ICP bolt or EVD placement
Key exclusion criteria (7 listed)
- Requiring decompressive craniotomy or post decompressive craniotomy
- Hyponatremia (sodium level < 125 mEq/L)
- Hypernatremia (sodium > 155 mmol/L)
- Serum osmolality ≤ 250 mOsm/kg
- Serum osmolality ≥ 320 mOsm/kg
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 |
|---|---|---|
| hypertonic saline3% hypertonic saline, dosed by ideal patient weight | Drug | hypertonic saline |
| MannitolAlso: OsmitrolMannitol 20% intravenous solution, dosed by patient's ideal body weight | Drug | Mannitol |
Primary outcome
Percent reduction of ICP from baseline
Time frame: 30 minutes from completion of medication administration
12 secondary outcomes
Time from study drug administration completion to ICP < 25 mmHg
Time frame: First 72 hours
Cumulative duration of ICP below 25 mmHg
Time frame: First 24 hours
Cumulative duration of ICP below 25 mmHg
Time frame: First 72 hours
Cumulative duration of cerebral perfusion pressure (CPP) above 60 mmHg
Time frame: First 24 hours
Cumulative duration of cerebral perfusion pressure (CPP) above 60 mmHg
Time frame: First 72 hours
Cumulative duration of regional oxygen partial pressure (pbtO2) > 20%
Time frame: two hours following each dose administration during the first 24 hours
Total dose of medications given
Time frame: First 24 hours; also over 3 days
Frequency of treatment failure
Time frame: First 72 hours
Frequency of rebound intracranial hypertension
Time frame: First 72 hours
Frequency of composite Major Adverse Events
Time frame: 3 days
Difference in inflammatory response
Time frame: Regular intervals over first 3 days
Difference in average pre-discharge stroke scale score
Time frame: hospital discharge (or 30 days if not discharged)
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 16 Mar 2017.
- Background: PubMed 9464749Shackford SR, Bourguignon PR, Wald SL, Rogers FB, Osler TM, Clark DE. Hypertonic saline resuscitation of patients with head injury: a prospective, randomized clinical trial. J Trauma. 1998 Jan;44(1):50-8. doi: 10.1097/00005373-199801000-00004.
- Background: PubMed 13687351BARRY KG, BERMAN AR. Mannitol infusion. III. The acute effect of the intravenous infusion of mannitol on blood and plasma volumes. N Engl J Med. 1961 May 25;264:1085-8. doi: 10.1056/NEJM196105252642105. No abstract available.
- Background: PubMed 17511539Brain Trauma Foundation; American Association of Neurological Surgeons; Congress of Neurological Surgeons; Joint Section on Neurotrauma and Critical Care, AANS/CNS; Bratton SL, Chestnut RM, Ghajar J, McConnell Hammond FF, Harris OA, Hartl R, Manley GT, Nemecek A, Newell DW, Rosenthal G, Schouten J, Shutter L, Timmons SD, Ullman JS, Videtta W, Wilberger JE, Wright DW. Guidelines for the management of severe traumatic brain injury. II. Hyperosmolar therapy. J Neurotrauma. 2007;24 Suppl 1:S14-20. doi: 10.1089/neu.2007.9994. No abstract available.
- Background: PubMed 10937895The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on Neurotrauma and Critical Care. Use of mannitol. J Neurotrauma. 2000 Jun-Jul;17(6-7):521-5. doi: 10.1089/neu.2000.17.521.
- Background: PubMed 11062300Bereczki D, Liu M, Prado GF, Fekete I. Cochrane report: A systematic review of mannitol therapy for acute ischemic stroke and cerebral parenchymal hemorrhage. Stroke. 2000 Nov;31(11):2719-22. doi: 10.1161/01.str.31.11.2719.
- Background: PubMed 9504569Qureshi AI, Suarez JI, Bhardwaj A, Mirski M, Schnitzer MS, Hanley DF, Ulatowski JA. Use of hypertonic (3%) saline/acetate infusion in the treatment of cerebral edema: Effect on intracranial pressure and lateral displacement of the brain. Crit Care Med. 1998 Mar;26(3):440-6. doi: 10.1097/00003246-199803000-00011.
- Background: PubMed 16720165Huang SJ, Chang L, Han YY, Lee YC, Tu YK. Efficacy and safety of hypertonic saline solutions in the treatment of severe head injury. Surg Neurol. 2006 Jun;65(6):539-46; discussion 546. doi: 10.1016/j.surneu.2005.11.019.
- Individual participant dataSharing planned: No
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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.
Achikam Oren-Grinberg, MD principal investigator
Beth Israel Deaconess Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing hypertonic saline and Mannitol in people with Elevated Intracranial Pressure, run by Beth Israel Deaconess Medical Center at 1 site in United States.
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 3 inclusion and 7 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 16 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
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?
Percent reduction of ICP from baseline (time frame: 30 minutes from completion of medication administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01108744, which also lists 7 linked publications.
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 16 Mar 2017.