Small-Volume, Patient-Specific, Balanced Hypertonic Fluid Protocol Validation

Randomized Controlled Trial for the Use of Patient Tailored Balanced Hypertonic Solutions in Patients With Cerebral Edema

Many patients with traumatic brain injuries (including strokes, blood clots, or other brain injuries) are given concentrated salt water solutions (hypertonic saline) in order to treat brain swelling (cerebral edema). Current therapies consist of a mixture of sodium and chloride, which can lead to high levels of serum chloride and increased total body water. High levels of chloride can cause acidosis, which can cause the body to function sub-optimally. Therefore, the investigators are proposing to use two concentrated solutions in these patients at the same time that will allow for a lower total volume of solution administration and reduce the rise in chloride to prevent acidosis. The main outcome will therefore be the patients sodium level, chloride level and serum pH.

Study Overview

• Status: Withdrawn
• Conditions: Cerebral Edema; Saline Solution, Hypertonic
• Intervention / Treatment: Drug: 3% Sodium Chloride; Drug: 23.4% Sodium Chloride; Drug: 8.4% Sodium Bicarbonate

• Study Type: Interventional
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University Hospital

Participation Criteria

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:

• Able to consent
• 18 years or older
• English speaking
• Clinical indication (intracranial hypertension from cerebral edema) for hypertonic fluid administration

Exclusion Criteria:

• Fails to consent
• < 18 years old
• Hypertonic therapy not indicated

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Therapy; This group will receive 3% hypertonic sodium chloride for the management of their cerebral edema. 3% Sodium Chloride is the generic name of this intravenous fluid preparation.	Drug: 3% Sodium Chloride; 3% sodium chloride will be infused into patients for the treatment or prevention of raised intracranial pressure
Experimental: Balanced Therapy; This group will undergo two simultaneous infusions. 23.4% sodium chloride and 8.4% sodium bicarbonate will be infused at the same time in various ratios for management of cerebral edema with a balanced approach	Drug: 23.4% Sodium Chloride; 23.4% sodium chloride will be infused into patients for the treatment or prevention of raised intracranial pressure; Drug: 8.4% Sodium Bicarbonate; 8.4% sodium bicarbonate will be infused into patients for the treatment or prevention of raised intracranial pressure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total volume of intravenous hypertonic fluid administered to the patient	Total hypertonic fluid volume administered to each group of patients measured in milliliters of fluid.	The fluid will be infused until the new serum sodium goal is achieved. This outcome measure will be assessed 1 week after study enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urine output	Urine output will be collected and measured quantitatively in milliliter units.	Urine output during active hypertonic fluid infusion will be measured. This outcome measure will be assessed 1 week after study enrollment

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Tim Angelotti, MD, PhD, Stanford University

Publications and helpful links

General Publications

• Wilcox CS. Regulation of renal blood flow by plasma chloride. J Clin Invest. 1983 Mar;71(3):726-35. doi: 10.1172/jci110820.
• Toung TJ, Nyquist P, Mirski MA. Effect of hypertonic saline concentration on cerebral and visceral organ water in an uninjured rodent model. Crit Care Med. 2008 Jan;36(1):256-61. doi: 10.1097/01.CCM.0000295306.52783.1E.
• Diringer MN, Zazulia AR. Osmotic therapy: fact and fiction. Neurocrit Care. 2004;1(2):219-33. doi: 10.1385/NCC:1:2:219.
• Erdman MJ, Riha H, Bode L, Chang JJ, Jones GM. Predictors of Acute Kidney Injury in Neurocritical Care Patients Receiving Continuous Hypertonic Saline. Neurohospitalist. 2017 Jan;7(1):9-14. doi: 10.1177/1941874416665744. Epub 2016 Aug 29.
• Neavyn MJ, Boyer EW, Bird SB, Babu KM. Sodium acetate as a replacement for sodium bicarbonate in medical toxicology: a review. J Med Toxicol. 2013 Sep;9(3):250-4. doi: 10.1007/s13181-013-0304-0.

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2017
• Primary Completion (Actual): January 1, 2020
• Study Completion (Actual): January 1, 2020

Study Registration Dates

• First Submitted: October 23, 2017
• First Submitted That Met QC Criteria: October 31, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): March 19, 2020
• Last Update Submitted That Met QC Criteria: March 17, 2020
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Edema
• Other Study ID Numbers: IRB-43653

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No plan to share data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No