Clinical trial NCT03204955: A Low ChloridE hyperTonic Solution for Brain Edema
Official title: Low-chloride Versus High-chloride Containing Hypertonic Solution for the Treatment of Subarachnoid Hemorrhage-Related Complications
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Subarachnoid Hemorrhage
Acute Kidney Injury
Keywords: Osmolar therapy
Acetate
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2017-07-02
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Once consented to the study, patients' serum chloride will be followed daily. Patients who will have a chloride concentration of 109mg/dL or above will be randomized to receive the blinded hypertonic solutions.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

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

Primary outcomes:
measure: Difference between serum chloride level on randomization day and the peak afterwards
timeFrame: Baseline, up to once daily during a patient's stay in the ICU, and up to 90 days
Secondary outcomes:
measure: Number of patients with acute kidney injury (AKI)
timeFrame: Patients' stay in the ICU, and up to 90 days
measure: All causes of in-hospital mortality.
timeFrame: Patients' stay in the ICU, and up to 90 days
measure: All causes of 90 day mortality.
timeFrame: Up to 90 days
measure: Change in intracerebral pressure (ICP) measured by ICP monitor following hypertonic treatment.
timeFrame: Continuous measurement as long as the patient has an indication for an ICP monitor, and up to 90 days
measure: Change in serum sodium level following the administration of the hypertonic solution.
timeFrame: Baseline, and daily during a patient's stay in the ICU, and up to 90 days
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital's Neurointensive Care Unit
state: Georgia
Study officials:
affiliation: Emory University
name: Owen Samuels, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sadan O, Singbartl K, Kraft J, Plancher JM, Greven ACM, Kandiah P, Pimentel C, Hall CL, Papangelou A, Asbury WH, Hanfelt JJ, Samuels O. Low-chloride- versus high-chloride-containing hypertonic solution for the treatment of subarachnoid hemorrhage-related complications: The ACETatE (A low ChloriE hyperTonic solution for brain Edema) randomized trial. J Intensive Care. 2020 May 4;8:32. doi: 10.1186/s40560-020-00449-0. eCollection 2020.
citation: Sadan O, Samuels O, Asbury WH, Hanfelt JJ, Singbartl K. Low-chloride versus high-chloride hypertonic solution for the treatment of subarachnoid hemorrhage-related complications (The ACETatE trial): study protocol for a pilot randomized controlled trial. Trials. 2018 Nov 14;19(1):628. doi: 10.1186/s13063-018-3007-7.