Potassium Supplementation in CKD (K+ in CKD)
Primary Purpose
Renal Insufficiency, Chronic, Potassium Depletion, Hypertension
Status
Recruiting
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Potassium Chloride
Potassium Citrate
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Renal Insufficiency, Chronic
Eligibility Criteria
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.
Sites / Locations
- Academic Medical Center AmsterdamRecruiting
- University Medical Center GroningenRecruiting
- Leiden University Medical CenterRecruiting
- Erasmus MCRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Experimental
Experimental
Arm Label
Placebo
Potassium Chloride
Potassium Citrate
Arm Description
Placebo
Experimental Arm 1 - Rationale is that most evidence for a positive effect of potassium comes from studies using potassium chloride
Experimental Arm 2 - Rationale for citrate is that recent evidence indicates that alkali treatment may also be renoprotective.
Outcomes
Primary Outcome Measures
Difference in estimated glomerular filtration rate (eGFR)
Secondary Outcome Measures
≥ 30% decrease in eGFR
Slope analysis (change in eGFR in ml/min/1.73 m2/year)
Doubling in serum creatinine or end-stage renal disease
Progression to next CKD or albuminuria class
Ambulatory (24-hour) blood pressure
24-hour albuminuria
Cardiovascular event
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
Incidence of hyperkalemia
NT-pro-BNP
Volume marker 1
Bioimpedance measures
Volume marker 2
Pulse-wave velocity
Cardiovascular marker 1
High-sensitive CRP
Cardiovascular marker 2
Full Information
NCT ID
NCT03253172
First Posted
August 15, 2017
Last Updated
January 15, 2022
Sponsor
Erasmus Medical Center
Collaborators
Dutch Kidney Foundation, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), University Medical Center Groningen, Leiden University Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT03253172
Brief Title
Potassium Supplementation in CKD
Acronym
K+ in CKD
Official Title
Renoprotective Effects of Potassium Supplementation in Chronic Kidney Disease (CKD)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2017 (Actual)
Primary Completion Date
October 1, 2024 (Anticipated)
Study Completion Date
October 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Erasmus Medical Center
Collaborators
Dutch Kidney Foundation, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), University Medical Center Groningen, Leiden University Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Insufficiency, Chronic, Potassium Depletion, Hypertension, Hyperkalemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
532 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Arm Title
Potassium Chloride
Arm Type
Experimental
Arm Description
Experimental Arm 1 - Rationale is that most evidence for a positive effect of potassium comes from studies using potassium chloride
Arm Title
Potassium Citrate
Arm Type
Experimental
Arm Description
Experimental Arm 2 - Rationale for citrate is that recent evidence indicates that alkali treatment may also be renoprotective.
Intervention Type
Dietary Supplement
Intervention Name(s)
Potassium Chloride
Intervention Description
Two potassium supplements with varying anions.
Intervention Type
Dietary Supplement
Intervention Name(s)
Potassium Citrate
Intervention Description
Potassium Citrate
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Difference in estimated glomerular filtration rate (eGFR)
Time Frame
Two years
Secondary Outcome Measure Information:
Title
≥ 30% decrease in eGFR
Time Frame
Two years
Title
Slope analysis (change in eGFR in ml/min/1.73 m2/year)
Time Frame
Two years
Title
Doubling in serum creatinine or end-stage renal disease
Time Frame
Two years
Title
Progression to next CKD or albuminuria class
Time Frame
Two years
Title
Ambulatory (24-hour) blood pressure
Time Frame
Two years
Title
24-hour albuminuria
Time Frame
Two years
Title
Cardiovascular event
Description
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
Time Frame
Two years
Title
All-cause mortality
Time Frame
Two years
Title
Incidence of hyperkalemia
Time Frame
Two years
Title
NT-pro-BNP
Description
Volume marker 1
Time Frame
Two years
Title
Bioimpedance measures
Description
Volume marker 2
Time Frame
Two years
Title
Pulse-wave velocity
Description
Cardiovascular marker 1
Time Frame
Two years
Title
High-sensitive CRP
Description
Cardiovascular marker 2
Time Frame
Two years
Other Pre-specified Outcome Measures:
Title
Effects of 2-week KCl supplementation on plasma potassium (mmol/l)
Description
Run-in outcome 1
Time Frame
Two weeks
Title
Incidence of Hyperkalemia after 2-week KCl supplementation
Description
Run-in outcome 2
Time Frame
Two weeks
Title
Effects of 2-week KCl supplementation on office blood pressure (mmHg)
Description
Run-in outcome 3
Time Frame
Two weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ewout J Hoorn, MD, PhD
Phone
+31107040704
Email
e.j.hoorn@erasmusmc.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ewout J Hoorn, MD, PhD
Organizational Affiliation
Erasmus Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Academic Medical Center Amsterdam
City
Amsterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Liffert Vogt, MD, PhD
Facility Name
University Medical Center Groningen
City
Groningen
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martin H De Borst, MD, PhD
Facility Name
Leiden University Medical Center
City
Leiden
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joris I Rotmans, MD, PhD
Facility Name
Erasmus MC
City
Rotterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ewout J Hoorn
Phone
+31107040704
First Name & Middle Initial & Last Name & Degree
Martin Gritter, MD
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
35609996
Citation
Gritter M, Wouda RD, Yeung SMH, Wieers MLA, Geurts F, de Ridder MAJ, Ramakers CRB, Vogt L, de Borst MH, Rotmans JI, Hoorn EJ; on behalf of K onsortium. Effects of Short-Term Potassium Chloride Supplementation in Patients with CKD. J Am Soc Nephrol. 2022 Sep;33(9):1779-1789. doi: 10.1681/ASN.2022020147. Epub 2022 May 24.
Results Reference
derived
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Potassium Supplementation in CKD
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