Double Blind Study of Hypertonic Saline vs Mannitol in the Management of Increased Intracranial Pressure (ICP). - Full Text View

Sponsor:	Beth Israel Deaconess Medical Center
Information provided by:	Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:	NCT01108744

Purpose

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:

Hypertonic saline therapy will result with fewer complications than mannitol
ICP reduction duration will be longer using hypertonic saline when compared with mannitol

Condition	Intervention
Elevated Intracranial Pressure	Drug: hypertonic saline Drug: mannitol

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Double Blind Study of Hypertonic Saline vs Mannitol in the Management of Increased Intracranial Pressure (ICP).

Resource links provided by NLM:

MedlinePlus related topics: High Blood Pressure

Drug Information available for: Mannitol

U.S. FDA Resources

Further study details as provided by Beth Israel Deaconess Medical Center:

Primary Outcome Measures:

Percent reduction of ICP from baseline [ Time Frame: 30 minutes from completion of medication administration ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time from study drug administration completion to ICP < 25 mmHg [ Time Frame: First 72 hours ] [ Designated as safety issue: No ]
Cumulative duration of ICP below 25 mmHg [ Time Frame: First 24 hours ] [ Designated as safety issue: No ]
Cumulative duration of ICP below 25 mmHg [ Time Frame: First 72 hours ] [ Designated as safety issue: No ]
Cumulative duration of cerebral perfusion pressure (CPP) above 60 mmHg [ Time Frame: First 24 hours ] [ Designated as safety issue: No ]
Cumulative duration of cerebral perfusion pressure (CPP) above 60 mmHg [ Time Frame: First 72 hours ] [ Designated as safety issue: No ]
Cumulative duration of regional oxygen partial pressure (pbtO2) > 20% [ Time Frame: two hours following each dose administration during the first 24 hours ] [ Designated as safety issue: No ]
Total dose of medications given [ Time Frame: First 24 hours; also over 3 days ] [ Designated as safety issue: No ]
Frequency of treatment failure [ Time Frame: First 72 hours ] [ Designated as safety issue: No ]
Treatment failure defined as ICP > 30 mmHg for > 30 minutes
Frequency of rebound intracranial hypertension [ Time Frame: First 72 hours ] [ Designated as safety issue: No ]
Rebound intracranial hypertension defined as ICP > 25 mmHg for more than 10 minutes following ICP stabilization
Frequency of composite Major Adverse Events [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
1. 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
2. hypotensive episodes (SBP < 90 mmHg for more than 10 minutes)
3. hemodynamic instability as measured by decrease of cardiac output by more than 15% within two hours following medication administration
4. pulmonary edema as defined by ELWI I> 10
Difference in inflammatory response [ Time Frame: Regular intervals over first 3 days ] [ Designated as safety issue: No ]
Determined by analysis of cytokine and inflammatory biomarkers.
Difference in average pre-discharge stroke scale score [ Time Frame: hospital discharge (or 30 days if not discharged) ] [ Designated as safety issue: No ]

Estimated Enrollment:	80
Study Start Date:	January 2012
Estimated Study Completion Date:	January 2014
Estimated Primary Completion Date:	January 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: hypertonic saline 3% hypertonic saline, dosed by ideal patient weight	Drug: hypertonic saline 3% hypertonic saline, dosed by ideal patient weight
Active Comparator: Mannitol 20% mannitol, dosed by patient's ideal body weight	Drug: mannitol 20% mannitol, dosed by patient's ideal body weight

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01108744

Contacts

Contact: Achikam Oren-Grinberg, MD

617-754-2675

agrinbe1@bidmc.harvard.edu

Locations

United States, Massachusetts
Beth Israel Deaconess Medical Center	Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Achikam Oren-Grinberg, MD 617-754-2675 agrinbe1@bidmc.harvard.edu
Principal Investigator: Achikam Oren-Grinberg, MD
Sub-Investigator: Ajith Thomas, MD
Sub-Investigator: Sandeep Kumar, MD
Sub-Investigator: Ekkehard Kasper, MD
Sub-Investigator: Daniel Talmor, MD, MPH
Sub-Investigator: Louis Caplan, MD
Sub-Investigator: Efstathios Papavassiliou, MD
Sub-Investigator: Michael Donnino, MD
Sub-Investigator: Michael Cocchi, MD
Sub-Investigator: Victor Novack, MD, PhD

Sponsors and Collaborators

Beth Israel Deaconess Medical Center

Investigators

Principal Investigator:

Achikam Oren-Grinberg, MD

Beth Israel Deaconess Medical Center

More Information

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.

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. No abstract available.

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. No abstract available. Erratum in: J Neurotrauma. 2008 Mar;25(3):276-8. multiple author names added.

[No authors listed] 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. Review.

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. Review.

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.

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.

Responsible Party:	Achikam Oren-Grinberg, MD, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:	NCT01108744 History of Changes
Other Study ID Numbers:	2009P-000313
Study First Received:	April 16, 2010
Last Updated:	October 18, 2010
Health Authority:	United States: Institutional Review Board

Keywords provided by Beth Israel Deaconess Medical Center:

clinical trial
mannitol
intracranial pressure (ICP)

hypertonic saline
cerebral edema
traumatic brain injury (TBI)

Additional relevant MeSH terms:

Intracranial Hypertension
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Mannitol
Diuretics, Osmotic

Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 09, 2012