Efficacy of Sodium Polystyrene Sulfonate in the Treatment of Hyperkaliemia in Pre-dialysis Patients (SKIP)

Efficacy of Sodium Polystyrene Sulfonate in the Treatment of Hyperkaliemia in Ambulatory Pre-dialysis Outpatients : a Randomized Triple-blind Placebo-controlled Trial

The purpose of this trial is to determine if sodium polystyrene sulfonate (SPS) is an effective treatment of mild hyperkalemia in chronic kidney disease patients followed at a pre-dialysis or nephrology outpatient clinic. Subjects will be randomized to one of two treatment arms: 30 g of placebo or SPS to be taken orally once daily for seven days. The change in serum potassium levels will be compared in both treatment groups. The proportion of subjects attaining normokalemia (3.5 to 5.0 mmol/L) after seven days of treatment will also be compared. Finally, side effects will be reported for each treatment arm.

Study Overview

• Status: Completed
• Conditions: Hyperkalemia; Chronic Kidney Failure
• Intervention / Treatment: Drug: Sodium polystyrene sulfonate; Drug: Lactose with carob gum

Detailed Description

Background

Hyperkalemia affects up to 10% of patients suffering from chronic kidney failure and up to 42% of patients with an estimated glomerular filtration rate lower than 20 mL/min/1.73m2. There is currently limited evidence on the use of sodium polystyrene sulfonate for the treatment of mild hyperkalemia. There are even fewer trials supporting its use over several days. To our knowledge, only one other study has evaluated its chronic use in fourteen patients, but hadn't controlled for recent changes in medications. Since its use is associated with adverse events that can considerably affect patients' quality of life, it appears primordial to better assess its place in the treatment of hyperkalemia in pre-dialysis patients.

Methods

The aim of this trial is to evaluate the use of sodium polystyrene sulfonate in the treatment of mild asymptomatic hyperkalemia in predialysis patients. Participants will be randomized to receive either 30 g of placebo or 30 g of SPS orally once daily for seven days. Serum potassium levels will be assessed at baseline and on the day following the last dose of their treatment. The change in serum potassium levels and the proportion of patients attaining normokalemia will be compared between study groups. The incidence of adverse events (nausea, diarrhea, constipation, electrolyte disorders) will also be reported. Participants will also be asked to fill out a food diary for 3 out of the 7 study days. This diary will be used to estimate each participant's average daily intake of potassium and therefore evaluate the similarity of diets between both intervention arms.

• Study Type: Interventional
• Enrollment (Anticipated): 38
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Maisonneuve-Rosemont Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Aged 18 years and over
• Outpatients followed at the pre-dialysis or nephrology clinics of Maisonneuve-Rosemont Hospital
• Subjects who have taken SPS in the past 7 days: serum potassium level measured for their regular followup of 4.5 to 5.5 mmol/L, inclusive, and serum potassium level of 5.0 to 5.9 mmol/L, inclusive, after a one week washout period
• Subjects who have not taken SPS in the past 7 days: serum potassium levels measured for their regular followup and on the day of randomisation of 5.0 to 5.9, inclusive

Exclusion Criteria:

• Subjects with a contraindication to SPS : known hypersensitivity to the product, history of obstructive bowel disease, patients at high risk of obstructive bowel disease
• Subjects unable of giving informed consent
• Subjects with severe or symptomatic hyperkalemia requiring a treatment
• Subjects on dialysis (hemodialysis or peritoneal dialysis)
• Women who are pregnant or breastfeeding
• Subjects who have had a change in the dosage of insulin in the past week, if this change represents more than 10% of the daily total dose or more than 5 units
• Subjects who stopped, started or changed the dosage of an angiotensin converting enzyme inhibitor, an angiotensin II receptor blocker or aliskiren in the past 60 days
• Subjects who stopped, started or changed the dosage of another medication affecting serum potassium levels in the past 30 days
• Subjects who have had an episode of decompensated heart failure in the past 30 days
• Subjects currently enrolled on another research protocol
• Subjects who are lactose intolerant

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sodium Polystyrene Sulfonate; 30 g sodium polystyrene sulfonate powder, mixed with water qs ad 150 ml, taken PO once daily for seven days	Drug: Sodium polystyrene sulfonate; Other Names: SPS; Kayexalate; Solystat
Placebo Comparator: Lactose with carob gum; 30 g placebo powder, mixed with water qs ad 150 ml, taken PO once daily for seven days	Drug: Lactose with carob gum; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum potassium levels from baseline	Compare the change in serum potassium levels from baseline in both treatment arms after 7 days of treatment with SPS or placebo 30 g once daily	After 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects attaining normokalemia (serum potassium level of 3.5 to 5.0 mmol/L) in each treatment arm	Compare the proportion of subjects attaining normokalemia (serum potassium level of 3.5 to 5.0 mmol/L) in each arm after one week of sodium polystyrene sulfonate or placebo	After 7 days
Number of patients with adverse events in each treatment group	Report the number of patients with adverse events, notably nausea, diarrhea, constipation, electrolyte disorders (hypomagnesemia, hypernatremia, hypophosphatemia, hypocalcemia, hypokalemia)	Up to 7 days

Collaborators and Investigators

• Sponsor: Maisonneuve-Rosemont Hospital
• Collaborators: Université de Montréal
• Investigators: Principal Investigator: Vincent Pichette, MD, Maisonneuve-Rosemont Hospital

Publications and helpful links

General Publications

• Natale P, Palmer SC, Ruospo M, Saglimbene VM, Strippoli GF. Potassium binders for chronic hyperkalaemia in people with chronic kidney disease. Cochrane Database Syst Rev. 2020 Jun 26;6(6):CD013165. doi: 10.1002/14651858.CD013165.pub2.

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: February 14, 2014
• First Submitted That Met QC Criteria: February 14, 2014
• First Posted (Estimate): February 17, 2014

Study Record Updates

• Last Update Posted (Estimate): October 3, 2014
• Last Update Submitted That Met QC Criteria: October 1, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Outpatients; Chronic kidney failure; Potassium; Hyperkalemia; Pre-dialysis; Sodium Polystyrene Sulfonate; Kayexalate
• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Water-Electrolyte Imbalance; Kidney Failure, Chronic; Renal Insufficiency; Hyperkalemia; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Polystyrene sulfonic acid
• Other Study ID Numbers: 13089