Clinical trial NCT01108744: Double Blind Study of Hypertonic Saline vs Mannitol in the Management of Increased Intracranial Pressure (ICP).
Official title: Double Blind Study of Hypertonic Saline vs Mannitol in the Management of Increased Intracranial Pressure (ICP).
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Elevated Intracranial Pressure
Keywords: clinical trial
mannitol
intracranial pressure (ICP)
hypertonic saline
cerebral edema
traumatic brain injury (TBI)
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
First posted: 2010-04-22
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. Hypertonic saline therapy will result with fewer complications than mannitol
2. 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?

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* elevated ICP requiring ICP monitoring
* ICP ≥ 25 mmHg 5 min after ICP bolt or EVD placement

Exclusion Criteria:

* 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

Primary outcomes:
measure: Percent reduction of ICP from baseline
timeFrame: 30 minutes from completion of medication administration
Secondary outcomes:
measure: Time from study drug administration completion to ICP < 25 mmHg
timeFrame: First 72 hours
measure: Cumulative duration of ICP below 25 mmHg
timeFrame: First 24 hours
measure: Cumulative duration of ICP below 25 mmHg
timeFrame: First 72 hours
measure: Cumulative duration of cerebral perfusion pressure (CPP) above 60 mmHg
timeFrame: First 24 hours
measure: Cumulative duration of cerebral perfusion pressure (CPP) above 60 mmHg
timeFrame: First 72 hours
measure: Cumulative duration of regional oxygen partial pressure (pbtO2) > 20%
timeFrame: two hours following each dose administration during the first 24 hours
measure: Total dose of medications given
timeFrame: First 24 hours; also over 3 days
measure: Frequency of treatment failure
timeFrame: First 72 hours
measure: Frequency of rebound intracranial hypertension
timeFrame: First 72 hours
measure: Frequency of composite Major Adverse Events
timeFrame: 3 days
measure: Difference in inflammatory response
timeFrame: Regular intervals over first 3 days
measure: Difference in average pre-discharge stroke scale score
timeFrame: hospital discharge (or 30 days if not discharged)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Achikam Oren-Grinberg, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: BARRY 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.
citation: Brain 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.
citation: The 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.
citation: Bereczki 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.
citation: Qureshi 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.
citation: Huang 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.