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

Sponsor

Beth Israel Deaconess Medical Center (Other)

Overall Status

Withdrawn

CT.gov ID

NCT01108744

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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:

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 or Disease	Intervention/Treatment	Phase
Elevated Intracranial Pressure	Drug: hypertonic saline Drug: Mannitol	N/A

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

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2012

Anticipated Primary Completion Date :

Jan 1, 2014

Anticipated Study Completion Date :

Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
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 Mannitol 20% intravenous solution, dosed by patient's ideal body weight Other Names: Osmitrol

Arm

Intervention/Treatment

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

Mannitol 20% intravenous solution, dosed by patient's ideal body weight

Other Names:

Osmitrol

Outcome Measures

Primary Outcome Measures

Percent reduction of ICP from baseline [30 minutes from completion of medication administration]

Secondary Outcome Measures

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