A Low ChloridE hyperTonic Solution for Brain Edema (ACETATE)

• ClinicalTrials.gov Identifier: NCT03204955
• Recruitment Status: Completed
• First Posted: July 2, 2017
• Last Update Posted: May 1, 2023
• Sponsor: Emory University
• Information provided by (Responsible Party): Owen Samuels, Emory University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Subarachnoid Hemorrhage; Acute Kidney Injury	Drug: Sodium chloride /sodium acetate (16.4%); Drug: Sodium chloride (23.4%); Drug: PlasmaLyte	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 59 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: A double-blinded-double-dummy design, where each dose of hypertonic solution will be administered along with a balanced solution in order to mask the difference in the volume between the two solutions.
• Primary Purpose: Treatment
• Official Title: Low-chloride Versus High-chloride Containing Hypertonic Solution for the Treatment of Subarachnoid Hemorrhage-Related Complications
• Actual Study Start Date: June 28, 2017
• Actual Primary Completion Date: September 30, 2018
• Actual Study Completion Date: September 30, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Sodium chloride /sodium acetate (16.4%); 50cc doses of sodium-chloride/sodium-acetate (16.4%) along with 30cc bag of dummy solution (PlasmaLyte).	Drug: Sodium chloride /sodium acetate (16.4%); Sodium Acetate is a sterile, nonpyrogenic solution of Sodium Acetate intended as an alternative to sodium chloride to provide sodium ion in parenteral (IV) fluid therapy. Sodium Chloride is sterile, nonpyrogenic hypertonic saline (concentrated sodium-chloride) solution for parenteral (IV) fluid therapy.; Drug: PlasmaLyte; PlasmaLyte is an isotonic IV solution that mimics human physiological plasma electrolyte concentrations, osmolality and pH.; Other Name: Placebo solution
Active Comparator: Sodium chloride (23.4%); 30cc per dose of sodium chloride (23.4%) along with 50cc dummy solution bag (PlasmaLyte)	Drug: Sodium chloride (23.4%); Sodium Chloride is sterile, nonpyrogenic hypertonic saline (concentrated sodium-chloride) solution for parenteral (IV) fluid therapy.; Drug: PlasmaLyte; PlasmaLyte is an isotonic IV solution that mimics human physiological plasma electrolyte concentrations, osmolality and pH.; Other Name: Placebo solution

Outcome Measures

Primary Outcome Measures :

1. Difference between serum chloride level on randomization day and the peak afterwards [ Time Frame: 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 :

1. Number of patients with acute kidney injury (AKI) [ Time Frame: 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.
2. All causes of in-hospital mortality. [ Time Frame: 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.
3. All causes of 90 day mortality. [ Time Frame: 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.
4. Change in intracerebral pressure (ICP) measured by ICP monitor following hypertonic treatment. [ Time Frame: 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.
5. Change in serum sodium level following the administration of the hypertonic solution. [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Georgia

Emory University Hospital's Neurointensive Care Unit

Atlanta, Georgia, United States, 30322

Sponsors and Collaborators

Emory University

Investigators

• Principal Investigator: Owen Samuels, MD; Emory University

More Information

Publications of Results:

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. Erratum In: J Intensive Care. 2020 Sep 1;8:66.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Owen Samuels, Associate Professor, Emory University
• ClinicalTrials.gov Identifier: NCT03204955
• Other Study ID Numbers: IRB00090456
• First Posted: July 2, 2017
• Last Update Posted: May 1, 2023
• Last Verified: April 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• 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

Keywords provided by Owen Samuels, Emory University:

Osmolar therapy; Acetate

Additional relevant MeSH terms:

Subarachnoid Hemorrhage; Acute Kidney Injury; Hemorrhage; Pathologic Processes; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Plasma-lyte 148; Ophthalmic Solutions; Pharmaceutical Solutions