Potassium Binders for Hyperkalemia

(KBindER Trial)

Overseen By Wei Ling Lau, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: University of California, Irvine

Must be taking: Potassium binders

Must not be taking: Sorbitol

Disqualifiers: Pregnancy, Psychiatric disorder, Dialysis, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing different medicines to lower high blood potassium in hospital patients. These medicines work by capturing potassium in the gut and removing it through stool. The goal is to find out which medicine works best for these patients. New medicines are being tested for their ability to manage high blood potassium by enhancing potassium removal through the digestive system.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use sorbitol while participating.

What data supports the effectiveness of the drug Patiromer for treating hyperkalemia?

Research suggests that patiromer, along with sodium zirconium cyclosilicate, may offer advantages over sodium polystyrene sulfonate (SPS) for treating hyperkalemia, as recommended by NICE for both acute and chronic cases. These drugs are emerging as effective options for managing high potassium levels, especially in patients with chronic kidney disease. ^{1 2 3 4 5}

Is the treatment with potassium binders generally safe for humans?

Potassium binders like sodium polystyrene sulfonate (SPS), patiromer, and sodium zirconium cyclosilicate (SZC) are used to manage high potassium levels and are generally considered safe, but there is limited evidence comparing their safety directly. They are recommended for both acute and chronic high potassium levels, although more research is needed to fully understand their safety in different settings. ^{1 2 3 4 5}

How does the drug Patiromer differ from other treatments for hyperkalemia?

Patiromer is a newer oral potassium binder that offers potential advantages over traditional treatments like sodium polystyrene sulfonate (SPS) by providing an alternative for long-term management of hyperkalemia, especially in patients with chronic kidney disease. It works by binding potassium in the gut, which helps lower potassium levels in the blood. ^{1 2 4 6 7}

Eligibility Criteria

This trial is for adults over 18 with high blood potassium levels (above 5.5 mEq/L) who can consent to participate. It's not for those with recent bowel surgery, blockages, certain blood issues mimicking high potassium, pregnant women, people with active psychiatric disorders or severe allergies to the drugs being tested.

Inclusion Criteria

Your blood potassium level is higher than 5.5 mEq/L.

I am 18 years old or older.

Patient able to provide written informed consent

Exclusion Criteria

I have diabetic ketoacidosis or high potassium levels due to a condition that can be treated directly.

I am currently experiencing a psychiatric disorder.

My high potassium levels are due to factors like tight fist clenching or a bad blood sample.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a one-time dose of one of the potassium binders or a nonspecific laxative

1 day

1 visit (in-person)

Immediate Follow-up

Blood potassium levels are checked at 2 and 4 hours after the dose, and participants complete a symptom and palatability questionnaire

4 hours

1 visit (in-person)

Extended Follow-up

Participants are monitored for any need for dialysis and changes in calcium, phosphorus, and magnesium levels

8 hours

Long-term Follow-up

The length of ER or hospital stay is compared for each study drug

Up to 60 days

Treatment Details

Interventions

• Patiromer (Cation Exchange Resin)
• Polyethylene Glycol 3350 (Cation Exchange Resin)
• Sodium Polystyrene Sulfonate Oral Suspension [SPS] (Cation Exchange Resin)
• Sodium zirconium cyclosilicate (Cation Exchange Resin)

Trial Overview The study compares three oral medications—Polyethylene Glycol 3350, Sodium Polystyrene Sulfonate [SPS], and Patiromer—to see which is best at lowering dangerously high potassium in hospital patients.

Participant Groups

Group I: Sodium zirconium cyclosilicate (Lokelma) Experimental Treatment 1 Intervention

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).

Group II: Sodium polystyrene sulfonate (Kayexalate) Experimental Treatment 1 Intervention

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).

Group III: Polyethylene glycol 3350 (MiraLax) Experimental Treatment 1 Intervention

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.

Group IV: Patiromer (Veltassa) Experimental Treatment 1 Intervention

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).

Who Is Running the Clinical Trial?

University of California, Irvine

Lead Sponsor

Trials

580

Recruited

4,943,000+

Findings from Research

Sodium polystyrene sulfonate (SPS) is the standard treatment for hyperkalemia, but newer agents like sodium zirconium cyclosilicate and patiromer may provide better options.

The introduction of these new agents could improve patient outcomes in managing hyperkalemia, suggesting a need for further evaluation of their safety and efficacy compared to SPS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potassium-Binding Agents for the Clinical Management of Hyperkalemia. Chaitman, M., Dixit, D., Bridgeman, MB.[2022]

In a study of 3,903 hospitalized patients, sodium polystyrene sulfonate (SPS) was found to reduce serum potassium levels more effectively than sodium zirconium cyclosilicate (SZC), with a mean reduction of 0.96 mEq/L compared to 0.78 mEq/L (P < 0.0001).

SPS also achieved resolution of hyperkalemia within 24 hours in a higher percentage of patients (74.9%) compared to SZC (68.8%) (P < 0.001), indicating that SPS may be the preferred choice for acute hyperkalemia treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of effectiveness and safety of sodium polystyrene sulfonate and sodium zirconium cyclosilicate for treatment of hyperkalemia in hospitalized patients. Sullivan, E., Ruegger, M., Dunne, I., et al.[2023]

Both sodium zirconium cyclosilicate (SZC) and calcium polystyrene sulfonate (CPS) effectively reduced potassium levels in patients with hyperkalaemia, with SZC showing a slightly greater reduction (1.24 mmol/L) compared to CPS (1.17 mmol/L) over a similar treatment duration (approximately 3 days).

While both treatments were equally effective, CPS was found to be slightly more cost-effective than SZC, although this came with increased staff input, highlighting the need for further randomized trials to better assess the benefits of newer treatments compared to established ones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperkalaemia and potassium binders: Retrospective observational analysis looking at the efficacy and cost effectiveness of calcium polystyrene sulfonate and sodium zirconium cyclosilicate. Huda, AB., Langford, C., Lake, J., et al.[2022]

Sodium polystyrene sulfonate (SPS) showed strong short-term efficacy and safety for reducing potassium levels in patients with chronic kidney disease (CKD), but requires careful long-term management due to potential gastrointestinal issues.

Patiromer may lower all-cause mortality in CKD patients with hyperkalemia, while sodium zirconium cyclosilicate (SZC) is effective for both short- and long-term potassium control, making it a promising option, especially when used with other medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of potassium binders in the treatment of patients with chronic kidney disease and hyperkalemia. Dong, L., Xu, W., Deng, Y., et al.[2022]

In a study involving 51 hemodialysis patients, both patiromer (PAT) and sodium polystyrene sulfonate (SPS) effectively reduced potassium levels, but SPS was significantly more effective than PAT in lowering potassium levels and prevalence of hyperkalemia.

Despite SPS being more effective, it had lower tolerability and compliance compared to PAT, indicating that while it works better, patients may find it harder to stick with the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy of patiromer and sodium polystyrene sulfonate on potassium levels in chronic haemodialysis patients: a randomized crossover trial. Jaques, DA., Stucker, F., Ernandez, T., et al.[2022]

In a study of 200 patients with acute hyperkalemia, both patiromer and sodium zirconium cyclosilicate (SZC) effectively reduced serum potassium levels, with patiromer lowering potassium by an average of -1.2 mEq/L and SZC by -0.8 mEq/L.

There was no significant difference in the effectiveness of patiromer compared to SZC for potassium reduction, indicating that both medications are viable options for managing acute hyperkalemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Patiromer Versus Sodium Zirconium Cyclosilicate for the Management of Acute Hyperkalemia. Rydell, A., Thackrey, C., Molki, M., et al.[2023]

Sodium zirconium cyclosilicate and patiromer are two new oral potassium binders that show promise as long-term treatment options for hyperkalemia, a common clinical issue.

These agents have demonstrated efficacy in several phase 3 short-term studies, indicating their potential effectiveness in managing elevated potassium levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hyperkalemia : what can we expect from new potassium-lowering drugs?]. Schmitt, R.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Potassium-Binding Agents for the Clinical Management of Hyperkalemia. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Comparison of effectiveness and safety of sodium polystyrene sulfonate and sodium zirconium cyclosilicate for treatment of hyperkalemia in hospitalized patients. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Hyperkalaemia and potassium binders: Retrospective observational analysis looking at the efficacy and cost effectiveness of calcium polystyrene sulfonate and sodium zirconium cyclosilicate. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of potassium binders in the treatment of patients with chronic kidney disease and hyperkalemia. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Comparative efficacy of patiromer and sodium polystyrene sulfonate on potassium levels in chronic haemodialysis patients: a randomized crossover trial. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Effectiveness of Patiromer Versus Sodium Zirconium Cyclosilicate for the Management of Acute Hyperkalemia. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

[Hyperkalemia : what can we expect from new potassium-lowering drugs?]. [2019]