Potassium Binders for Hyperkalemia

(KBindER Trial)

Overseen By Wei Ling Lau, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, Irvine

Must be taking: Potassium binders

Must not be taking: Sorbitol

Disqualifiers: Pregnancy, Psychiatric disorder, Dialysis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests different treatments for hyperkalemia, a condition where blood contains too much potassium. Researchers aim to evaluate the effectiveness of three oral potassium binders—patiromer, sodium polystyrene sulfonate, and sodium zirconium cyclosilicate—in lowering potassium levels. Additionally, the trial examines polyethylene glycol 3350 (a laxative) to determine if addressing constipation aids in managing hyperkalemia. Suitable participants are hospital patients with high blood potassium levels (over 5.5 mEq/L). As a Phase 4 trial, the treatments have already received FDA approval and demonstrated effectiveness, and this research seeks to understand their benefits for more patients.

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 is the safety track record for these treatments?

A previous study found patiromer to be safe for treating high potassium levels. It proved effective and easy for patients to manage. Some experienced mild side effects, such as changes in calcium levels, but these were not serious.

Research has shown that sodium zirconium cyclosilicate is also safe for managing high potassium. Its safety profile was similar to a placebo, indicating it did not cause more side effects than a sugar pill, suggesting it is easy for patients to handle.

Polyethylene glycol 3350, often used as a laxative, is generally safe. Some individuals reported diarrhea, but this usually resolved with dose adjustments. It is effective with a low risk of serious side effects.

However, sodium polystyrene sulfonate has raised safety concerns. Reports indicate serious stomach and intestinal issues, including intestinal damage, making it a riskier choice compared to the others.

Overall, patiromer and sodium zirconium cyclosilicate have strong safety records. Polyethylene glycol 3350 is also safe with minor side effects. However, sodium polystyrene sulfonate may pose more significant risks. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for hyperkalemia because they offer unique approaches compared to traditional options like sodium polystyrene sulfonate. Patiromer (Veltassa) and sodium zirconium cyclosilicate (Lokelma) are novel potassium binders that work by binding excess potassium in the gut, thus lowering potassium levels more efficiently and with potentially fewer side effects. Unlike other treatments, polyethylene glycol 3350 (MiraLax) addresses hyperkalemia by targeting constipation, which can contribute to high potassium levels, offering a different mechanism of action. These diverse approaches provide promising alternatives for managing hyperkalemia more effectively.

What evidence suggests that this trial's treatments could be effective for hyperkalemia?

Research has shown that patiromer, one of the treatments in this trial, effectively lowers potassium levels in individuals with hyperkalemia. It performs well in both emergencies and over extended periods. Another treatment option, sodium zirconium cyclosilicate, also reduces potassium levels rapidly, with studies noting a significant drop within 48 hours. Sodium polystyrene sulfonate, also under study, has a smaller effect, lowering potassium by less than 1 mEq/L in urgent situations. Polyethylene glycol 3350, included in this trial, primarily treats constipation and doesn't directly lower potassium, but it may help by relieving constipation, which can contribute to high potassium levels. Each treatment in this trial has managed potassium levels to varying degrees of effectiveness. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Patiromer
• Polyethylene Glycol 3350
• Sodium Polystyrene Sulfonate Oral Suspension [SPS]
• Sodium zirconium cyclosilicate

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.

How Is the Trial Designed?

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).

Patiromer is already approved in United States, European Union for the following indications:

Approved in United States as Veltassa for:

• Hyperkalemia in adults and geriatric patients

Approved in European Union as Veltassa for:

• Hyperkalemia

Who Is Running the Clinical Trial?

University of California, Irvine

Lead Sponsor

Trials

580

Recruited

4,943,000+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5388568/

Systematic Review and Meta-Analysis of Patiromer ... Both agents exhibited statistically and clinically significant reductions in potassium for the primary endpoint of this meta-analysis. Given the adverse effect ...

2. fda.gov fda.gov/media/175678/download

Application 205739 S-038|Veltassa|Page 1 of 50 Multiple Dose Study to Evaluate the Pharmacodynamic Effects, Safety, and Tolerability of Veltassa. (Patiromer Sorbitex Calcium) for Oral Suspension in Children ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9292454/

Clinical Efficacy, Safety, Tolerability, and Real-World Data ... Patiromer has been shown to be safe and effective in patients with hyperkalemia, but there are still many questions to be answered and different populations ...

4. sciencedirect.com sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/patiromer

Patiromer - an overview Clinical trial data has proven patiromer effective in lowering serum potassium both in emergency and ambulatory clinical settings [60–64]. Patiromer effectively ...

5. australianprescriber.tg.org.au australianprescriber.tg.org.au/articles/patiromer-sorbitex-calcium-for-hyperkalaemia.html

Patiromer sorbitex calcium for hyperkalaemia All doses of patiromer reduced the mean potassium concentration within the first four weeks of the trial. For example, a dose of 12.6 g twice ...

6. ema.europa.eu ema.europa.eu/en/documents/rmp/veltassa-epar-risk-management-plan_en.pdf

eu risk management plan for veltassa® (patiromer) - EMA Post-marketing safety data. MedDRA terms. MedDRA PTs: Hypercalcaemia. Blood calcium increased. Blood calcium abnormal. Notes: AE=Adverse event ...

7. veltassa.com veltassa.com/pi

HIGHLIGHTS OF PRESCRIBING INFORMATION These ... pharmacodynamic and safety data in pediatric patients aged 12 years ... The chemical name for patiromer sorbitex calcium is cross-linked polymer of calcium.

8. cda-amc.ca cda-amc.ca/sites/default/files/cdr/complete/SR0665-combined.pdf

Patiromer (Veltassa) The objective of this report was to perform a systematic review of the beneficial and harmful effects of patiromer (as patiromer sorbitex calcium: 8.4 g, 16.8 g ...