Potassium Correction for RAAS Optimization in Chronic Kidney Disease

ConditionsChronic Kidney Diseases Hyperkalemia Hypertension

Trial statusRecruiting

Trial phasePhase 4

Trial typeInterventional

Biological sexAll

Age18+

SponsorUniversity Medical Center Groningen

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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;

Disqualifiers

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

Trial design

Design model

Crossover

Treatments tested in this trial

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.
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.

Treatment groups

44 Participants

are divided into 2 treatment groups

Group A: PatiromerExperimental treatment 1 intervention

Group B: PlaceboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

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.

Time frame