A Low ChloridE hyperTonic Solution for Brain Edema

Phase 1

Completed

• Conditions: Acute Kidney Injury; Subarachnoid Hemorrhage
• Interventions: Drug: Sodium chloride (23.4%); Drug: Sodium chloride /sodium acetate (16.4%); Drug: PlasmaLyte

• Registration Number: NCT03204955
• Lead Sponsor: Emory University

Brief Summary

This pilot study will compare the two hypertonic solutions currently used for subarachnoid hemorrhage (SAH) - related complications and to determine if the reduction of chloride load is safer, and as efficacious as the classic hypertonic solution.

Detailed Description

This pilot study aimed to collect high-quality randomized and prospective information to help plan a future, larger multicenter trial. The study will compare the two hypertonic solutions currently used for subarachnoid hemorrhage (SAH) - related complications and to determine if the reduction of chloride load by using a sodium acetate and sodium chloride mixture can lead to a relative reduction of serum chloride, reduce kidney injury, and as efficacious as the classic hypertonic solution.

Hyperosmolar therapy is one of the mainstay treatments for SAH-related cerebral edema and vasospasm, in order to reduce delayed cerebral ischemia. Recent evidence from the literature correlates high chloride load when applying IV fluids with worse outcome in a variety of critically-ill patients. Hypertonic saline, with which most hyperosmolar treatment is done, contains a supra-physiologic chloride load. It is possible that by changing the hypertonic solution to a "chloride-lean" one, the study team would be able to reduce the side effects of hypertonic sodium-chloride without losing its efficacy in treating SAH-related complications.

Study Timeline

• Study Start: 2017-06-28
• Study First Submitted: 2017-06-28
• Study First Submitted QC: 2017-06-28
• Study First Posted: 2017-07-02
• Primary Completion: 2018-09-30
• Study Completion: 2018-09-30
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-27
• Last Update Posted: 2023-05-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 59

Inclusion Criteria

• Spontaneous SAH with an identified aneurysmal source as identified on neuroimaging obtained at admission to Emory University Hospital or with imaging at an outside hospital
• Age ≥ 18 years

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Exclusion Criteria

• SAH related to non-aneurysmal vascular anomaly
• SAH thought due to trauma
• SAH occurring in relation to another medical procedure (cardiac catheterization, LVAD placement, etc.)
• SAH with a negative workup for cause ("angio-negative")
• Patients who arrive in a brain-death state or in a devastating clinical status that will be presumed to lead to brain death or early withdrawal of treatment
• Patient who suffer from end-stage renal disease at baseline and who are routinely treated with dialysis
• Known pregnancy

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sodium chloride (23.4%)	Sodium chloride (23.4%)	30cc per dose of sodium chloride (23.4%) along with 50cc dummy solution bag (PlasmaLyte)
Sodium chloride /sodium acetate (16.4%)	Sodium chloride /sodium acetate (16.4%)	50cc doses of sodium-chloride/sodium-acetate (16.4%) along with 30cc bag of dummy solution (PlasmaLyte).
Sodium chloride (23.4%)	PlasmaLyte	30cc per dose of sodium chloride (23.4%) along with 50cc dummy solution bag (PlasmaLyte)
Sodium chloride /sodium acetate (16.4%)	PlasmaLyte	50cc doses of sodium-chloride/sodium-acetate (16.4%) along with 30cc bag of dummy solution (PlasmaLyte).

Primary Outcome Measures

Name	Time	Method
Difference between serum chloride level on randomization day and the peak afterwards	Baseline, up to once daily during a patient's stay in the ICU, and up to 90 days	Serum chloride levels will be measured as part of standard of care. Difference between serum chloride level on randomization day and the peak afterwards will be calculated.

Secondary Outcome Measures

Name	Time	Method
All causes of in-hospital mortality.	Patients' stay in the ICU, and up to 90 days	All causes of in-hospital mortality, including withdrawal of treatment or discharge to a hospice facility, will be recorded.
All causes of 90 day mortality.	Up to 90 days	All causes of mortality, 90 days post admission day, including withdrawal of treatment or discharge to a hospice facility, will be recorded.
Number of patients with acute kidney injury (AKI)	Patients' stay in the ICU, and up to 90 days	AKI diagnosis will be done on the basis of clinical parameters (serum creatinine ≥ 1.5 times baseline or ≥0.3 mg/dl and urine output (\<0.5 ml/kg/h for 6 hours) according to Kidney Disease Improving Global Outcomes (KDIGO). Number of patients with acute kidney injury (AKI) will be recorded.
Change in intracerebral pressure (ICP) measured by ICP monitor following hypertonic treatment.	Continuous measurement as long as the patient has an indication for an ICP monitor, and up to 90 days	Change in intracerebral pressure (ICP) following the administration of the hypertonic solution will be recorded.
Change in serum sodium level following the administration of the hypertonic solution.	Baseline, and daily during a patient's stay in the ICU, and up to 90 days	Serum sodium levels will be measured as part of standard of care. Difference between serum sodium level on randomization day and the peak afterwards will be calculated.

Trial Locations

Locations (1)

Emory University Hospital's Neurointensive Care Unit; 🇺🇸 Atlanta, Georgia, United States