Potassium Correction for RAAS Optimization in Chronic Kidney Disease

NCT06256991 | Recruiting Phase 4 DMC

• 1 other identifier: 17237
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this placebo-controlled, double-blinded cross-over trial is to test whether patiromer, compared with placebo, better enables up-titration of RAAS-blocker treatment in patients with chronic kidney disease stage 3b/4. The main questions it aims to answer are:

• Does patiromer allow uptitration of irbesartan, resulting in a significant reduction in albuminuria and blood pressure?
• Does patiromer allow uptitration of irbesartan, resulting in a significant reduction in blood pressure? The trial contains the following interventions:
• Participants will be switched from their ACEi/ARB to a standardised dose of irbesartan (150 mg/d).
• During two 12-week study periods, participants will receive either patiromer 8.4 g/d or placebo. The order of study periods is randomized.
• At the start of each study period irbesartan will be up-titrated to 300 mg/d.
• After 1 and 6 weeks, at both periods, plasma potassium will be measured and the irbesartan dose will be reduced to 150 mg/d in case plasma potassium exceeds 5.0 mmol/L.
• At 12 weeks from the start of the study period, the endpoints will be assessed.
• Between the two study periods, there is a 6-week washout. Irbesartan dose during the wash-out period will be 150mg/d. After washout, participants will switch from the patiromer arm to the placebo arm or vice versa.

Conditions

Chronic Kidney Diseases; Hyperkalemia; Hypertension

Outcome Measures

Primary Outcomes (1)

• Albumin-creatinine ratio (ACR)

  The primary study endpoint is the difference in ACR in 24-hour urine at the end of each study visit, compared to the ACR at the start of the study period. This is a continuous variable that will be presented quantitatively. In case of non-normal distribution, this parameter will be log-transformed. The primary hypothesis test will be the difference between placebo and treatment groups after 2 periods.

  At the end of both 12-week study periods (patiromer and placebo)

Secondary Outcomes (5)

• Blood pressure

  At the end of both 12-week study periods (patiromer and placebo)

• Plasma potassium

  At the end of both 12-week study periods (patiromer and placebo)

• Kidney function

  At the end of both 12-week study periods (patiromer and placebo)

• Irbesartan dose

  At the end of both 12-week study periods (patiromer and placebo)

• Adverse events

  At the end of both 12-week study periods (patiromer and placebo)

Study Arms (2)

Patiromer

EXPERIMENTAL

All participants will receive patiromer 8.4g/d (powder for oral suspension) during one of the two 12-week study periods. Following a 6-week washout, participants will switch from the patiromer arm to the placebo arm or vice versa (cross-over design).

Drug: Patiromer 8400 MG [Veltassa]

Placebo

PLACEBO COMPARATOR

All participants will receive placebo 8.4g/d (powder for oral suspension) during one of the two 12-week study periods. Following a 6-week washout, participants will switch from the patiromer arm to the placebo arm or vice versa (cross-over design).

Drug: Placebo

Interventions

Patiromer 8400 MG [Veltassa] DRUG

Patiromer is a cation-exchanging polymer intended for oral intake that is not resorbed from the gastro-intestinal tract. Patiromer has been approved by the European Medicines Agency (EMA) and is available for clinical use in The Netherlands for the indication of hyperkalemia in adults. It contains calcium-sorbitol complex as a counter-ion. Patiromer increases the faecal excretion of potassium in the gastro-intestinal lumen by exchange with part of the calcium. This results in a lower concentration of free potassium in the gastro-intestinal lumen, reducing in turn plasma potassium concentration. After initiation of patiromer, a clinically significant reduction in plasma potassium can be observed at around 7 hours, the effect persists for approximately 24 hours. Patiromer is excreted by the fecal route, 24-48 hrs after ingestion. Since patiromer is not absorbed or metabolized by the body, other drugs are not expected to influence the efficacy of patiromer.

Patiromer

Placebo DRUG

Placebo is a powder with a similar appearance, smell, and taste as patiromer, but without and clinically detectable effects. It is intended for oral intake.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years;
• CKD stage 3b-4 (eGFR 15-44 mL/min/1.73 m2)
• Albumin-creatinine ratio \>3 mg/mmol, or proteinuria \>0.05g/24u, or protein-creatinine ratio \> 5mg/mmol
• Systolic blood pressure \>130 mmHg or use of one or more antihypertensive drugs;
• Serum K+ 4.0-5.0 mmol/L;
• On sub-maximal dose ACEi/ARB

You may not qualify if:

• prior ACEi/ARB dose reduction due to a drop in eGFR by \>25% in the last year;
• history of severe hyperkalaemia (\>6.0 mmol/L) in the last year;
• pregnancy or breastfeeding
• life expectancy \<12 months
• the use of lithium, potassium-sparing diuretics, potassium supplements, trimethoprim or NSAIDS
• kidney transplant recipients, or diagnosis of autosomal dominant polycystic kidney disease or other non-glomerular kidney disease

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Amsterdam University Medical Center: collaborator
• Frisius Medisch Centrum: collaborator
• Isala: collaborator
• Vifor Pharma, Inc.: collaborator
• Dutch Kidney Foundation: collaborator
• Health Holland: collaborator

Study Sites (1)

University Medical Center Groningen

Groningen, Netherlands

RECRUITING

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Hyperkalemia; Hypertension

Interventions

patiromer

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Liffert Vogt, prof. dr.

  Amsterdam University Medical Centre

  PRINCIPAL INVESTIGATOR

• Aaltje Adema, dr.

  Frisius Medisch Centrum

  PRINCIPAL INVESTIGATOR

• Femke Waanders, dr.

  Isala Zwolle

  PRINCIPAL INVESTIGATOR

• Martin de Borst, prof. dr.

  University Medical Center Groningen

  STUDY CHAIR

Central Study Contacts

Martin de Borst, prof. dr.

CONTACT

+31503616161; m.h.de.borst@umcg.nl

Caspar van Lieshout, MD

CONTACT

+31503616161; c.j.van.lieshout@umcg.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Participants, care providers and investigators will be blinded regarding the use of patiromer vs. placebo during the two study periods. Irbesartan will be open label.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2024
• First Posted: February 13, 2024
• Study Start: April 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 19, 2025

Record last verified: 2025-12

Locations

NL (1)