<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03253172</url>
  </required_header>
  <id_info>
    <org_study_id>NL60825.078.17</org_study_id>
    <secondary_id>MEC-2017-226</secondary_id>
    <secondary_id>CP16.01</secondary_id>
    <nct_id>NCT03253172</nct_id>
  </id_info>
  <brief_title>Potassium Supplementation in CKD</brief_title>
  <acronym>K+ in CKD</acronym>
  <official_title>Renoprotective Effects of Potassium Supplementation in Chronic Kidney Disease (CKD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Erasmus Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Dutch Kidney Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Medical Center Groningen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Leiden University Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Erasmus Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The current high-sodium, low-potassium diet contributes to the high prevalence of high blood&#xD;
      pressure (hypertension). Indeed, the anti-hypertensive effects of potassium supplementation&#xD;
      are well-established. Hypertension is even more prevalent and resistant in patients with&#xD;
      chronic kidney disease (CKD) and contributes to further decline in kidney function. Four&#xD;
      recent epidemiological studies (published 2014 - 2016) showed that higher dietary potassium&#xD;
      intake was associated with better renal outcomes. All studies recommended an intervention&#xD;
      study with potassium supplementation in patients with CKD, but this has not been performed.&#xD;
      The aim of this study is to study the renoprotective effect of potassium supplementation in&#xD;
      patients with CKD (stage 3b or 4, i.e. estimated glomerular filtration rate [eGFR] 15 - 45&#xD;
      ml/min/1.73 m2).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 1, 2017</start_date>
  <completion_date type="Anticipated">October 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">October 1, 2024</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Difference in estimated glomerular filtration rate (eGFR)</measure>
    <time_frame>Two years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>≥ 30% decrease in eGFR</measure>
    <time_frame>Two years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Slope analysis (change in eGFR in ml/min/1.73 m2/year)</measure>
    <time_frame>Two years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Doubling in serum creatinine or end-stage renal disease</measure>
    <time_frame>Two years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression to next CKD or albuminuria class</measure>
    <time_frame>Two years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ambulatory (24-hour) blood pressure</measure>
    <time_frame>Two years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>24-hour albuminuria</measure>
    <time_frame>Two years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiovascular event</measure>
    <time_frame>Two years</time_frame>
    <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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality</measure>
    <time_frame>Two years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of hyperkalemia</measure>
    <time_frame>Two years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NT-pro-BNP</measure>
    <time_frame>Two years</time_frame>
    <description>Volume marker 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bioimpedance measures</measure>
    <time_frame>Two years</time_frame>
    <description>Volume marker 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulse-wave velocity</measure>
    <time_frame>Two years</time_frame>
    <description>Cardiovascular marker 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>High-sensitive CRP</measure>
    <time_frame>Two years</time_frame>
    <description>Cardiovascular marker 2</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Effects of 2-week KCl supplementation on plasma potassium (mmol/l)</measure>
    <time_frame>Two weeks</time_frame>
    <description>Run-in outcome 1</description>
  </other_outcome>
  <other_outcome>
    <measure>Incidence of Hyperkalemia after 2-week KCl supplementation</measure>
    <time_frame>Two weeks</time_frame>
    <description>Run-in outcome 2</description>
  </other_outcome>
  <other_outcome>
    <measure>Effects of 2-week KCl supplementation on office blood pressure (mmHg)</measure>
    <time_frame>Two weeks</time_frame>
    <description>Run-in outcome 3</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">532</enrollment>
  <condition>Renal Insufficiency, Chronic</condition>
  <condition>Potassium Depletion</condition>
  <condition>Hypertension</condition>
  <condition>Hyperkalemia</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Potassium Chloride</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Experimental Arm 1 - Rationale is that most evidence for a positive effect of potassium comes from studies using potassium chloride</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Potassium Citrate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Experimental Arm 2 - Rationale for citrate is that recent evidence indicates that alkali treatment may also be renoprotective.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Potassium Chloride</intervention_name>
    <description>Two potassium supplements with varying anions.</description>
    <arm_group_label>Potassium Chloride</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Potassium Citrate</intervention_name>
    <description>Potassium Citrate</description>
    <arm_group_label>Potassium Citrate</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  CKD 3b or 4 (45 - 15 ml/min/1.73 m2)&#xD;
&#xD;
          -  Δ eGFR (as estimated by the CKD-EPI equation) &gt; 2 ml/min/1.73 m2/year (in preceding ≥&#xD;
             1 year with at least 3 measurements)&#xD;
&#xD;
          -  Hypertension (defined as office blood pressure &gt; 140/90 mmHg or use of&#xD;
             anti-hypertensive medication)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hyperkalemia (serum potassium &gt; 5.5 mmol/l) at study visit V0&#xD;
&#xD;
          -  Medical reasons to continue dual RAAS-blockade, mineralocorticoid receptor blockers,&#xD;
             potassium-sparing diuretics, or oral potassium binders.&#xD;
&#xD;
          -  Patients with previous history of ventricular cardiac arrhythmia&#xD;
&#xD;
          -  Patients with a life expectancy &lt; 6 months&#xD;
&#xD;
          -  Expected initiation of renal replacement therapy &lt; 2 years&#xD;
&#xD;
          -  Incapacitated subjects&#xD;
&#xD;
          -  Women who are pregnant, breastfeeding or consider pregnancy in the coming 2 years.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ewout J Hoorn, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Erasmus Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ewout J Hoorn, MD, PhD</last_name>
    <phone>+31107040704</phone>
    <email>e.j.hoorn@erasmusmc.nl</email>
  </overall_contact>
  <location>
    <facility>
      <name>Academic Medical Center Amsterdam</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Liffert Vogt, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>University Medical Center Groningen</name>
      <address>
        <city>Groningen</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Martin H De Borst, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Leiden University Medical Center</name>
      <address>
        <city>Leiden</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joris I Rotmans, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Erasmus MC</name>
      <address>
        <city>Rotterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ewout J Hoorn</last_name>
      <phone>+31107040704</phone>
    </contact>
    <investigator>
      <last_name>Martin Gritter, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>August 15, 2017</study_first_submitted>
  <study_first_submitted_qc>August 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 17, 2017</study_first_posted>
  <last_update_submitted>January 15, 2022</last_update_submitted>
  <last_update_submitted_qc>January 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 19, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Erasmus Medical Center</investigator_affiliation>
    <investigator_full_name>Ewout Hoorn</investigator_full_name>
    <investigator_title>Coordinating PI</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Renal Insufficiency</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
    <mesh_term>Hyperkalemia</mesh_term>
    <mesh_term>Hypokalemia</mesh_term>
    <mesh_term>Potassium Deficiency</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Potassium Citrate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03253172
org study id: NL60825.078.17
secondary id: MEC-2017-226
secondary id: CP16.01
nct id: NCT03253172
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Difference in estimated glomerular filtration rate (eGFR)
time frame: Two years
measure: ≥ 30% decrease in eGFR
time frame: Two years
measure: Slope analysis (change in eGFR in ml/min/1.73 m2/year)
time frame: Two years
measure: Doubling in serum creatinine or end-stage renal disease
time frame: Two years
measure: Progression to next CKD or albuminuria class
time frame: Two years
measure: Ambulatory (24-hour) blood pressure
time frame: Two years
measure: 24-hour albuminuria
time frame: Two years
measure: Cardiovascular event
time frame: Two years
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
measure: All-cause mortality
time frame: Two years
measure: Incidence of hyperkalemia
time frame: Two years
measure: NT-pro-BNP
time frame: Two years
description: Volume marker 1
measure: Bioimpedance measures
time frame: Two years
description: Volume marker 2
measure: Pulse-wave velocity
time frame: Two years
description: Cardiovascular marker 1
measure: High-sensitive CRP
time frame: Two years
description: Cardiovascular marker 2
measure: Effects of 2-week KCl supplementation on plasma potassium (mmol/l)
time frame: Two weeks
description: Run-in outcome 1
measure: Incidence of Hyperkalemia after 2-week KCl supplementation
time frame: Two weeks
description: Run-in outcome 2
measure: Effects of 2-week KCl supplementation on office blood pressure (mmHg)
time frame: Two weeks
description: Run-in outcome 3
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo
arm group label: Potassium Chloride
arm group type: Experimental
description: Experimental Arm 1 - Rationale is that most evidence for a positive effect of potassium comes from studies using potassium chloride
arm group label: Potassium Citrate
arm group type: Experimental
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: Potassium Chloride
description: Two potassium supplements with varying anions.
arm group label: Potassium Chloride
intervention type: Dietary Supplement
intervention name: Potassium Citrate
description: Potassium Citrate
arm group label: Potassium Citrate
intervention type: Dietary Supplement
intervention name: Placebo
description: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ewout J Hoorn, MD, PhD
role: Principal Investigator
affiliation: Erasmus Medical Center
last name: Ewout J Hoorn, MD, PhD
phone: +31107040704
email: e.j.hoorn@erasmusmc.nl
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
investigator: 
country: Netherlands
responsible party type: Principal Investigator
investigator affiliation: Erasmus Medical Center
investigator full name: Ewout Hoorn
investigator title: Coordinating PI
mesh term: Renal Insufficiency
mesh term: Renal Insufficiency, Chronic
mesh term: Hyperkalemia
mesh term: Hypokalemia
mesh term: Potassium Deficiency
mesh term: Potassium Citrate
sharing ipd: Undecided