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

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

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

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 Summary:

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?


Sponsor: Beth Israel Deaconess Medical Center

Current Primary Outcome: Percent reduction of ICP from baseline [ Time Frame: 30 minutes from completion of medication administration ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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 ]
    Treatment failure defined as ICP > 30 mmHg for > 30 minutes
  • Frequency of rebound intracranial hypertension [ Time Frame: 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 [ Time Frame: 3 days ]
    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 ]
    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) ]


Original Secondary Outcome: Same as current

Information By: Beth Israel Deaconess Medical Center

Dates:
Date Received: April 16, 2010
Date Started: January 2012
Date Completion: January 2014
Last Updated: March 14, 2017
Last Verified: March 2017