Comparison of Potassium Binders in the ER (KBindER)

Compare efficacy of 3 oral potassium binders (cation exchange resins) on lowering blood potassium, in hospital patients with acute hyperkalemia.

Study Overview

• Status: Recruiting
• Conditions: Acute Hyperkalemia; Oral Potassium Binders
• Intervention / Treatment: Drug: Polyethylene Glycol 3350; Drug: Sodium Polystyrene Sulfonate Oral Suspension [SPS]; Drug: Patiromer; Drug: Sodium zirconium cyclosilicate

Detailed Description

Adult patients presenting to the Emergency Room or currently hospitalized at UC Irvine (not in ICU level of care) with plasma potassium >5.5 mEq/L (who meet inclusion/exclusion criteria and provide written informed consent) will be randomized to a one-time dose of one of the following oral medications:

1. Sodium polystyrene sulfate (SPS)
2. Patiromer (Veltassa)
3. Sodium zirconium cyclosilicate (Lokelma)
4. Nonspecific laxative: polyethylene glycol 3350 (MiraLax)

Participants will receive standard-of-care hyperkalemia therapy as well.

Blood potassium will be checked at 2 and 4 hours after dose of study drug. Participants will complete a symptom and palatability questionnaire at 4 hours.

The purpose of this research study is to determine the effects of various potassium binders (SPS, patiromer, zirconium) vs a non-specific laxative (MiraLax) in hospital patients found to have elevated blood potassium > 5.5 mEq/L. Hyperkalemia is a fairly common electrolyte disorder with varying levels of severity. Moderate hyperkalemia is in the range 5.5-5.9 mEq/L while severe hyperkalemia is ≥6.0 mEq/L or if patient is symptomatic: muscle weakness/paralysis or with EKG changes (e.g., peaked T waves, widening QRS, arrhythmias including ventricular fibrillation or asystole). Hyperkalemia is most commonly associated with kidney insufficiency, metabolic acidosis, and the use of medications such as renin-angiotensin-aldosterone system inhibitors.

In an emergency, the main goal is to reverse adverse cardiac effects and shift potassium into cells using interventions such as insulin/glucose and albuterol. However, these are only temporary measures. To remove potassium from the body, agents or interventions that may be used include cation exchange resins (potassium binders), loop diuretics, or dialysis. For over 50 years the only available oral cation exchange resin has been sodium polystyrene sulfonate. In recent years, two new agents (patiromer and zirconium) have been approved by the FDA for chronic management of hyperkalemia.

The cation exchange resins have not been studied head-to-head for acute hyperkalemia. This is a critical knowledge gap since acute hyperkalemia poses a significant burden on the healthcare system. In claims data analysis of 80,000 patients, half with hyperkalemia and half without, the patients with hyperkalemia had 4 times higher rate of inpatient admissions, 7 times longer average length of stay, and 30-day hospital readmission rate 14.21% vs 9.86% in the non-hyperkalemia cohort. The findings from our study will help inform decision-making guidelines for the treatment of acute hyperkalemia.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Wei Ling Lau, MD; Phone Number: 714-456-5142; Email: wllau@uci.edu

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • Recruiting
      • University of California, Irvine Medical Center
      • Contact: Wei Ling Lau, MD; Phone Number: 714-456-5142; Email: wllau@uci.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Plasma potassium > 5.5 mEq/L
• Age ≥18 years
• Patient able to provide written informed consent

Exclusion Criteria:

• Recent bowel surgery
• Ileus or bowel obstruction
• Pseudohyperkalemia signs and symptoms, such as excessive fist clenching, hemolyzed blood specimen, severe leukocytosis or thrombocytosis
• Pregnancy
• Active psychiatric disorder
• Diabetic ketoacidosis or hyperkalemia caused by any condition for which a therapy directed against the underlying cause of hyperkalemia would be a better treatment option
• Dialysis session expected within 4 hours after randomization
• History of hypersensitivity to sodium polystyrene sulfonate resin or patiromer
• Concurrent use of sorbitol (due to increased risk of intestinal necrosis when used with sodium polystyrene sulfonate)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Polyethylene glycol 3350 (MiraLax); Participants will be randomized to one of four study arms. They will receive one dose of the study drug. One study arm is the nonspecific laxative MiraLax (one dose of 17g). Since constipation can contribute to hyperkalemia, this arm will study the effect of treating constipation instead of direct cation exchange for potassium in the gut.	Drug: Polyethylene Glycol 3350; Nonspecific laxative comparison group.; Other Names: MiraLax
Experimental: Sodium polystyrene sulfonate (Kayexalate); Participants will be randomized to one of four study arms. They will receive one dose of the study drug. The potassium binder drugs of interest include sodium polystyrene sulfonate (one dose of 30g), patiromer (one dose of 25.2g), and sodium zirconium cyclosilicate (one dose of 15g).	Drug: Sodium Polystyrene Sulfonate Oral Suspension [SPS]; Potassium binder to treat hyperkalemia.; Other Names: Kayexalate
Experimental: Patiromer (Veltassa); Participants will be randomized to one of four study arms. They will receive one dose of the study drug. The potassium binder drugs of interest include sodium polystyrene sulfonate (one dose of 30g), patiromer (one dose of 25.2g), and sodium zirconium cyclosilicate (one dose of 15g).	Drug: Patiromer; Potassium binder to treat hyperkalemia.; Other Names: Veltassa
Experimental: Sodium zirconium cyclosilicate (Lokelma); Participants will be randomized to one of four study arms. They will receive one dose of the study drug. The potassium binder drugs of interest include sodium polystyrene sulfonate (one dose of 30g), patiromer (one dose of 25.2g), and sodium zirconium cyclosilicate (one dose of 15g).	Drug: Sodium zirconium cyclosilicate; Potassium binder to treat hyperkalemia.; Other Names: Lokelma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in blood potassium level	The investigators will compare the change in blood potassium after administration of the study drug, in the acute setting.	Plasma potassium level measured at 2 and 4 hours after study drug was administered

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of ER or hospital stay	The investigators will compare length of ER or hospital stay associated with each study drug, obtained from medical chart review.	Up to 60 days after study drug was administered
Change in calcium, phosphorus and magnesium	The investigators will compare the effect of each study drug on blood calcium, phosphorus and magnesium levels, in the acute setting.	Measured at 2 and 4 hours after study drug was administered
Dialysis yes/no within 8 hours	The investigators will assess whether dialysis was needed to manage hyperkalemia, and whether dialysis requirement was affected by the study drug given. This will be assessed from medical chart review.	Within 8 hours of study drug being administered
Palatability and side effects (patient subjective rating)	Participants will complete a 1-page brief survey assessing for potential study drug side effects including bloating, nausea, diarrhea and palpitations (answers are yes/no). Participants will also rate the palatability of the study drug using a 1-5 scale, with 5 being the best score (most palatable and easy to swallow).	4 hours after study drug was administered

Collaborators and Investigators

• Sponsor: University of California, Irvine

Publications and helpful links

General Publications

• Leon SJ, Harasemiw O, Tangri N. New therapies for hyperkalemia. Curr Opin Nephrol Hypertens. 2019 May;28(3):238-244. doi: 10.1097/MNH.0000000000000500.
• Betts KA, Woolley JM, Mu F, Xiang C, Tang W, Wu EQ. The Cost of Hyperkalemia in the United States. Kidney Int Rep. 2017 Nov 14;3(2):385-393. doi: 10.1016/j.ekir.2017.11.003. eCollection 2018 Mar.

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2020
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: September 30, 2020
• First Submitted That Met QC Criteria: October 6, 2020
• First Posted (Actual): October 14, 2020

Study Record Updates

• Last Update Posted (Actual): October 27, 2023
• Last Update Submitted That Met QC Criteria: October 25, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Emergency Department
• Additional Relevant MeSH Terms: Metabolic Diseases; Water-Electrolyte Imbalance; Hyperkalemia; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Chelating Agents; Sequestering Agents; Laxatives; Polyethylene glycol 3350; Polystyrene sulfonic acid
• Other Study ID Numbers: HS# 2020-5780

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will not be shared. De-identified dataset can be made available to other researchers, please contact PI Dr. Lau.

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