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

March 14, 2017 updated by: Achikam Orin-Grinberg, Beth Israel Deaconess Medical Center

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

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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 Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Percent reduction of ICP from baseline
Time Frame: 30 minutes from completion of medication administration
30 minutes from completion of medication administration

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time from study drug administration completion to ICP < 25 mmHg
Time Frame: First 72 hours
First 72 hours
Cumulative duration of ICP below 25 mmHg
Time Frame: First 24 hours
First 24 hours
Cumulative duration of ICP below 25 mmHg
Time Frame: First 72 hours
First 72 hours
Cumulative duration of cerebral perfusion pressure (CPP) above 60 mmHg
Time Frame: First 24 hours
First 24 hours
Cumulative duration of cerebral perfusion pressure (CPP) above 60 mmHg
Time Frame: First 72 hours
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
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
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
First 72 hours
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
First 72 hours
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
3 days
Difference in inflammatory response
Time Frame: Regular intervals over first 3 days
Determined by analysis of cytokine and inflammatory biomarkers.
Regular intervals over first 3 days
Difference in average pre-discharge stroke scale score
Time Frame: hospital discharge (or 30 days if not discharged)
hospital discharge (or 30 days if not discharged)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beth Israel Deaconess Medical Center

Investigators

  • Principal Investigator: Achikam Oren-Grinberg, MD, Beth Israel Deaconess Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2012

Primary Completion (Anticipated)

January 1, 2014

Study Completion (Anticipated)

January 1, 2014

Study Registration Dates

First Submitted

April 16, 2010

First Submitted That Met QC Criteria

April 21, 2010

First Posted (Estimate)

April 22, 2010

Study Record Updates

Last Update Posted (Actual)

March 16, 2017

Last Update Submitted That Met QC Criteria

March 14, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2009P000313

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Elevated Intracranial Pressure

Clinical Trials on hypertonic saline

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in South Africa

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe