K+ in CKD: Potassium Supplementation in CKD

Sponsor

Erasmus Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT03253172

Collaborator

Dutch Kidney Foundation (Other), Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) (Other), University Medical Center Groningen (Other), Leiden University Medical Center (Other)

532

Enrollment

Locations

Arms

Anticipated Duration (Months)

133

Patients Per Site

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The current high-sodium, low-potassium diet contributes to the high prevalence of high blood pressure (hypertension). Indeed, the anti-hypertensive effects of potassium supplementation are well-established. Hypertension is even more prevalent and resistant in patients with chronic kidney disease (CKD) and contributes to further decline in kidney function. Four recent epidemiological studies (published 2014 - 2016) showed that higher dietary potassium intake was associated with better renal outcomes. All studies recommended an intervention study with potassium supplementation in patients with CKD, but this has not been performed. The aim of this study is to study the renoprotective effect of potassium supplementation in patients with CKD (stage 3b or 4, i.e. estimated glomerular filtration rate [eGFR] 15 - 45 ml/min/1.73 m2).

Condition or Disease	Intervention/Treatment	Phase
Renal Insufficiency, Chronic Potassium Depletion Hypertension Hyperkalemia	Dietary Supplement: Potassium Chloride Dietary Supplement: Potassium Citrate Dietary Supplement: Placebo	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

532 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Renoprotective Effects of Potassium Supplementation in Chronic Kidney Disease (CKD)

Actual Study Start Date :

Jul 1, 2017

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Oct 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo	Dietary Supplement: Placebo Placebo
Experimental: Potassium Chloride Experimental Arm 1 - Rationale is that most evidence for a positive effect of potassium comes from studies using potassium chloride	Dietary Supplement: Potassium Chloride Two potassium supplements with varying anions.
Experimental: Potassium Citrate Experimental Arm 2 - Rationale for citrate is that recent evidence indicates that alkali treatment may also be renoprotective.	Dietary Supplement: Potassium Citrate Potassium Citrate

Arm

Intervention/Treatment

Placebo Comparator: Placebo

Placebo

Dietary Supplement: Placebo

Placebo

Experimental: Potassium Chloride

Experimental Arm 1 - Rationale is that most evidence for a positive effect of potassium comes from studies using potassium chloride

Dietary Supplement: Potassium Chloride

Two potassium supplements with varying anions.

Experimental: Potassium Citrate

Experimental Arm 2 - Rationale for citrate is that recent evidence indicates that alkali treatment may also be renoprotective.

Dietary Supplement: Potassium Citrate

Potassium Citrate

Outcome Measures

Primary Outcome Measures

Difference in estimated glomerular filtration rate (eGFR) [Two years]

Secondary Outcome Measures

≥ 30% decrease in eGFR [Two years]
Slope analysis (change in eGFR in ml/min/1.73 m2/year) [Two years]
Doubling in serum creatinine or end-stage renal disease [Two years]
Progression to next CKD or albuminuria class [Two years]
Ambulatory (24-hour) blood pressure [Two years]
24-hour albuminuria [Two years]
Cardiovascular event [Two years]
Coronary heart disease death, fatal myocardial infarction, fatal stroke and other cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, unstable angina, resuscitated cardiac arrest
All-cause mortality [Two years]
Incidence of hyperkalemia [Two years]
NT-pro-BNP [Two years]
Volume marker 1
Bioimpedance measures [Two years]
Volume marker 2
Pulse-wave velocity [Two years]
Cardiovascular marker 1
High-sensitive CRP [Two years]
Cardiovascular marker 2

Other Outcome Measures

Effects of 2-week KCl supplementation on plasma potassium (mmol/l) [Two weeks]
Run-in outcome 1
Incidence of Hyperkalemia after 2-week KCl supplementation [Two weeks]
Run-in outcome 2
Effects of 2-week KCl supplementation on office blood pressure (mmHg) [Two weeks]
Run-in outcome 3

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

CKD 3b or 4 (45 - 15 ml/min/1.73 m2)
Δ eGFR (as estimated by the CKD-EPI equation) > 2 ml/min/1.73 m2/year (in preceding ≥ 1 year with at least 3 measurements)
Hypertension (defined as office blood pressure > 140/90 mmHg or use of anti-hypertensive medication)

Exclusion Criteria:

Hyperkalemia (serum potassium > 5.5 mmol/l) at study visit V0
Medical reasons to continue dual RAAS-blockade, mineralocorticoid receptor blockers, potassium-sparing diuretics, or oral potassium binders.
Patients with previous history of ventricular cardiac arrhythmia
Patients with a life expectancy < 6 months
Expected initiation of renal replacement therapy < 2 years
Incapacitated subjects
Women who are pregnant, breastfeeding or consider pregnancy in the coming 2 years.

Contacts and Locations

Locations

	Site	City	Country
1	Academic Medical Center Amsterdam	Amsterdam	Netherlands
2	University Medical Center Groningen	Groningen	Netherlands
3	Leiden University Medical Center	Leiden	Netherlands
4	Erasmus MC	Rotterdam	Netherlands