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

Elevated Intracranial Pressure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01108744
• Other study ID #: 2009P000313
• Status: Withdrawn
• Phase: N/A
• First received: April 16, 2010
• Last updated: March 14, 2017
• Start date: January 2012
• Est. completion date: January 2014

Study information

• Verified date: March 2017
• Source: Beth Israel Deaconess Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. Hypertonic saline therapy will result with fewer complications than mannitol

2. ICP reduction duration will be longer using hypertonic saline when compared with mannitol

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?

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Elevated Intracranial Pressure
• Intracranial Hypertension

Intervention

Drug:
• hypertonic saline
3% hypertonic saline, dosed by ideal patient weight
• Mannitol
Mannitol 20% intravenous solution, dosed by patient's ideal body weight

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Beth Israel Deaconess Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (7)

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. — View 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. Review. — View 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. Erratum in: J Neurotrauma. 2008 Mar;25(3):276-8. multiple author names added. — View 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. — View 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. — View 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent reduction of ICP from baseline		30 minutes from completion of medication administration
Secondary	Time from study drug administration completion to ICP < 25 mmHg		First 72 hours
Secondary	Cumulative duration of ICP below 25 mmHg		First 24 hours
Secondary	Cumulative duration of ICP below 25 mmHg		First 72 hours
Secondary	Cumulative duration of cerebral perfusion pressure (CPP) above 60 mmHg		First 24 hours
Secondary	Cumulative duration of cerebral perfusion pressure (CPP) above 60 mmHg		First 72 hours
Secondary	Cumulative duration of regional oxygen partial pressure (pbtO2) > 20%		two hours following each dose administration during the first 24 hours
Secondary	Total dose of medications given		First 24 hours; also over 3 days
Secondary	Frequency of treatment failure	Treatment failure defined as ICP > 30 mmHg for > 30 minutes	First 72 hours
Secondary	Frequency of rebound intracranial hypertension	Rebound intracranial hypertension defined as ICP > 25 mmHg for more than 10 minutes following ICP stabilization	First 72 hours
Secondary	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	3 days
Secondary	Difference in inflammatory response	Determined by analysis of cytokine and inflammatory biomarkers.	Regular intervals over first 3 days
Secondary	Difference in average pre-discharge stroke scale score		hospital discharge (or 30 days if not discharged)