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

This study has been withdrawn prior to enrollment.
(Timeline to consent prior to intervention start was unfeasible.)
Sponsor:
Information provided by (Responsible Party):
Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:
NCT01108744
First received: April 16, 2010
Last updated: September 5, 2012
Last verified: September 2012
  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:

  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

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:


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 ]

Enrollment: 0
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Investigators
Principal Investigator: Achikam Oren-Grinberg, MD Beth Israel Deaconess Medical Center
  More Information

Publications:

Responsible Party: 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: September 5, 2012
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 September 16, 2014