<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/NCT03809884</url>
  </required_header>
  <id_info>
    <org_study_id>20180873-01H</org_study_id>
    <nct_id>NCT03809884</nct_id>
  </id_info>
  <brief_title>Dietary Counseling or Potassium Supplement to Increase Potassium Intake in Patients With High Blood Pressure</brief_title>
  <official_title>Diet or Additional Supplement to Increase Potassium Intake: An Adaptive Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ottawa Hospital Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ottawa Hospital Research Institute</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>
      High blood pressure is the leading cause of cardiovascular disease worldwide. Many medicines&#xD;
      are available to lower blood pressures successfully, as well as many non-medical options,&#xD;
      such as dietary changes. Some effective dietary changes include decreasing sodium and&#xD;
      increasing potassium in the diet. A lot of focus has been on sodium intake yet; potassium&#xD;
      intake in the diet remains low amongst adult Canadians. Excellent data exist in the published&#xD;
      research reporting that increasing potassium intake, either as diet or even as supplements,&#xD;
      reduces blood pressure and reduces risk of cardiovascular outcomes such as stroke.&#xD;
&#xD;
      The overall purpose of this study is to reveal the most effective way of increasing&#xD;
      potassium, amongst participants with high blood pressure whose existing intake of potassium&#xD;
      is low. In the first stage, participants with high blood pressure and proven low potassium&#xD;
      intake will receive dietary counselling. If after 4 weeks, there has not been a desired&#xD;
      increase in potassium intake, the patients will be prescribed an additional potassium&#xD;
      supplement.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      High blood pressure is the leading cause of cardiovascular disease worldwide, including in&#xD;
      Canada. The prevalence of high blood pressure is steadily rising, with growing and ageing&#xD;
      population. Many medicines are available to decrease blood pressures successfully, as well as&#xD;
      many non-medical options, such as dietary changes and exercise. There is a marked preference&#xD;
      amongst patients, reiterated in a recent Hypertension Canada report, for more research into&#xD;
      methods for controlling blood pressure without medicines or to reduce the burden of taking&#xD;
      many pills to control high blood pressure. Indeed, effective options do exist, especially&#xD;
      with diet, specifically decreasing sodium and increasing potassium in diet. Both these&#xD;
      recommendations are also made by organizations worldwide including the World Health&#xD;
      Organization as well as Hypertension Canada. Though a lot of focus has been on sodium intake&#xD;
      in the public health outreach, even the potassium intake in diet remains woefully low amongst&#xD;
      adult Canadians. Excellent data exist in the published research reporting that increasing&#xD;
      potassium intake, either as diet or even as supplements, reduces blood pressure and reduces&#xD;
      risk of cardiovascular outcomes such as stroke. The advice most often provided is to 'eat&#xD;
      more fruits and vegetables' which does not get translated into concrete change.&#xD;
&#xD;
      The Investigators propose to do a clinical trial in two stages (as an adaptive trial design).&#xD;
      In the first stage, participants with high blood pressure and proven low potassium intake&#xD;
      (measured on the basis of collecting urine for 24 hours) will get individually tailored&#xD;
      dietary advice, reinforced by weekly supportive phone/email support. If at 4 weeks, there has&#xD;
      not been a desired increase in potassium intake, the patients will be prescribed an&#xD;
      additional potassium supplement. Testing at 4 weeks will be conducted again to confirm the&#xD;
      efficacy of the potassium supplement. Final measurements will be planned at 52 weeks to&#xD;
      observe and measure the persistence of the effect of diet or additional supplement.&#xD;
      Concurrent measurements of sodium intake, blood pressure, participant satisfaction, safety&#xD;
      measures will also be done.&#xD;
&#xD;
      The results of the study would help determine the most effective method of increasing&#xD;
      potassium intake, thus reducing blood pressure, need for blood pressure lowering medicines,&#xD;
      at the same time potentially increasing participant satisfaction. The current guidelines&#xD;
      recommend changes in diet (not supplement) to increase potassium intake, hence the two stage&#xD;
      design will only add supplements if the most rigorous dietary advice does not work. The&#xD;
      Investigators have received letters of support from the World Hypertension League and&#xD;
      Hypertension Canada in support of the research design and for dissemination and&#xD;
      implementation of the findings.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 1, 2019</start_date>
  <completion_date type="Anticipated">November 2025</completion_date>
  <primary_completion_date type="Anticipated">February 2025</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Successful increase in potassium intake</measure>
    <time_frame>4 weeks</time_frame>
    <description>As estimated by 24 hour urine results at 4 weeks, achieving a urinary sodium &gt; 90 mmol/day.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Persistence of increase in potassium intake at 52 weeks</measure>
    <time_frame>52 weeks</time_frame>
    <description>As estimated by comparison of persistence of change in potassium intake (as estimated by 24 hour urine results) from 4 weeks to 52 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hyperkalemia Events</measure>
    <time_frame>4 weeks to 52 weeks</time_frame>
    <description>Any episodes of hyperkalemia (as defined as a serum potassium greater than the 5.1 mmol/L)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gastrointestinal Events</measure>
    <time_frame>4 weeks to 52 weeks</time_frame>
    <description>Gastrointestinal side effects, specifically changes in bowel habits, belching and/or flatulence; abdominal pain or cramps.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>Dietary Counselling</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All enrolled patients will undergo a 1:1 counselling with a registered dietitian (with possible inclusion of family members, as appropriate). The dietitian will undertake an assessment of the comorbidities (e.g. diabetes), dietary intake, dietary habits (e.g. eating out, food preparation, socio-cultural aspects) and provide an individually tailored strategy to increase potassium in the diet. Secondly, on a weekly basis, the dietitian will contact the patient by telephone, or electronically (as preferred by the patient) to reinforce the advice and provide support/advice as necessary.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Potassium Citrate Supplement</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients who are not able to successfully increase their potassium intake at 4 weeks with dietary counselling will receive potassium citrate supplements. They will receive oral potassium supplementation in the form of 50 to 100 mmol of potassium citrate (as 25 to 50 ml of the liquid solution).</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Dietary Counselling</intervention_name>
    <description>Individually tailored strategy to increase potassium in the diet.</description>
    <arm_group_label>Dietary Counselling</arm_group_label>
    <arm_group_label>Potassium Citrate Supplement</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Potassium Citrate</intervention_name>
    <description>Dosing of 50 to 100 mmol of potassium citrate per day (as 25 to 50 ml of the liquid solution).</description>
    <arm_group_label>Potassium Citrate Supplement</arm_group_label>
    <other_name>K-Citra</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provides signed and dated informed consent form&#xD;
&#xD;
          2. Diagnosis of hypertension (either on treatment; or not on treatment with an ambulatory&#xD;
             blood pressure monitor (ABPM)- daytime systolic blood pressure (SBP) &gt; 140 or&#xD;
             diastolic blood pressure (DBP) &gt; 90)&#xD;
&#xD;
          3. Male or female, aged 18 and greater (women of child bearing potential must use highly&#xD;
             effective contraception (e.g. combined oral contraceptives, patch, vaginal ring,&#xD;
             injectables, and implants; intrauterine device (IUD) or intrauterine system (IUS);&#xD;
             vasectomy of male partner and tubal ligation)&#xD;
&#xD;
          4. 24-Hour Urine K &lt; 60 mmol/day&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Serum Potassium &lt; 3.3 or &gt; 5.1 mmol/L&#xD;
&#xD;
          2. Glomerular Filtration Rate &lt; 45 ml/min/1.73m2&#xD;
&#xD;
          3. Primary hyperaldosteronism&#xD;
&#xD;
          4. Pregnancy or lactation&#xD;
&#xD;
          5. Psychiatric disorder which, in the opinion of the investigator, would interfere with&#xD;
             the study, or inability to give consent&#xD;
&#xD;
          6. Severe Liver disease&#xD;
&#xD;
          7. Metabolic Alkalosis (HCO3 &gt; 32 mmol/L)&#xD;
&#xD;
          8. Exclude patients who need to be started on renin-angiotensin-aldosterone blockade in&#xD;
             the first 3 months&#xD;
&#xD;
          9. Gastrointestinal disorder (e.g. delayed gastric emptying, dysphagia,&#xD;
             oesophageal/gastric/duodenal ulcer)&#xD;
&#xD;
         10. Presence of cardiac disease (sever myocardial damage, heart failure, or clinical&#xD;
             changes in congestive heart failure, ejection fraction &lt;35%)&#xD;
&#xD;
         11. Uncontrolled diabetes mellitus (HbA1C &gt;12%)&#xD;
&#xD;
         12. Acute dehydration&#xD;
&#xD;
         13. Extensive tissue damage (burns)&#xD;
&#xD;
         14. Increased hypersensitivity to potassium (e.g. paramyotonia congenital or adynamia&#xD;
             episodica hereditaria)&#xD;
&#xD;
         15. Patients taking other potassium supplements for another indication (eg. kidney stones)&#xD;
&#xD;
         16. Acidosis (pH&lt;7.11)&#xD;
&#xD;
         17. Adrenal insufficiency&#xD;
&#xD;
         18. Allergies to any of the investigational product ingredients (medicinal and non-&#xD;
             medicinal)&#xD;
&#xD;
         19. Patients on any of the following medications should be on a stable dose: angiotensin&#xD;
             converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, beta-blockers,&#xD;
             mineralocorticoid receptor antagonists, amiloride, non steroidal antiinflammatory&#xD;
             drugs (NSAIDs), beta-blockers, digoxin, and heparin&#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>Swapnil Hiremath, MD MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Ottawa Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jennifer Biggs, RN</last_name>
    <phone>613-738-8400</phone>
    <phone_ext>82514</phone_ext>
    <email>jbiggs@ohri.ca</email>
  </overall_contact>
  <location>
    <facility>
      <name>Ottawa Hospital Research Institute</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1H 1A2</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jennifer Biggs, RN</last_name>
      <phone>613-738-8400</phone>
      <phone_ext>82514</phone_ext>
      <email>jbiggs@ohri.ca</email>
    </contact>
    <investigator>
      <last_name>Swapnil Hiremath, MD PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Marcel Ruzicka, MD MPH</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>December 13, 2018</study_first_submitted>
  <study_first_submitted_qc>January 16, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <last_update_submitted>April 12, 2023</last_update_submitted>
  <last_update_submitted_qc>April 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>High blood pressure</keyword>
  <keyword>Potassium</keyword>
  <keyword>Potassium Citrate</keyword>
  <keyword>Dietary Counselling</keyword>
  <keyword>Hypertension</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</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>No</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/NCT03809884
org study id: 20180873-01H
nct id: NCT03809884
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
High blood pressure is the leading cause of cardiovascular disease worldwide. Many medicines
      are available to lower blood pressures successfully, as well as many non-medical options,
      such as dietary changes. Some effective dietary changes include decreasing sodium and
      increasing potassium in the diet. A lot of focus has been on sodium intake yet; potassium
      intake in the diet remains low amongst adult Canadians. Excellent data exist in the published
      research reporting that increasing potassium intake, either as diet or even as supplements,
      reduces blood pressure and reduces risk of cardiovascular outcomes such as stroke.

      The overall purpose of this study is to reveal the most effective way of increasing
      potassium, amongst participants with high blood pressure whose existing intake of potassium
      is low. In the first stage, participants with high blood pressure and proven low potassium
      intake will receive dietary counselling. If after 4 weeks, there has not been a desired
      increase in potassium intake, the patients will be prescribed an additional potassium
      supplement.
High blood pressure is the leading cause of cardiovascular disease worldwide, including in
      Canada. The prevalence of high blood pressure is steadily rising, with growing and ageing
      population. Many medicines are available to decrease blood pressures successfully, as well as
      many non-medical options, such as dietary changes and exercise. There is a marked preference
      amongst patients, reiterated in a recent Hypertension Canada report, for more research into
      methods for controlling blood pressure without medicines or to reduce the burden of taking
      many pills to control high blood pressure. Indeed, effective options do exist, especially
      with diet, specifically decreasing sodium and increasing potassium in diet. Both these
      recommendations are also made by organizations worldwide including the World Health
      Organization as well as Hypertension Canada. Though a lot of focus has been on sodium intake
      in the public health outreach, even the potassium intake in diet remains woefully low amongst
      adult Canadians. Excellent data exist in the published research reporting that increasing
      potassium intake, either as diet or even as supplements, reduces blood pressure and reduces
      risk of cardiovascular outcomes such as stroke. The advice most often provided is to 'eat
      more fruits and vegetables' which does not get translated into concrete change.

      The Investigators propose to do a clinical trial in two stages (as an adaptive trial design).
      In the first stage, participants with high blood pressure and proven low potassium intake
      (measured on the basis of collecting urine for 24 hours) will get individually tailored
      dietary advice, reinforced by weekly supportive phone/email support. If at 4 weeks, there has
      not been a desired increase in potassium intake, the patients will be prescribed an
      additional potassium supplement. Testing at 4 weeks will be conducted again to confirm the
      efficacy of the potassium supplement. Final measurements will be planned at 52 weeks to
      observe and measure the persistence of the effect of diet or additional supplement.
      Concurrent measurements of sodium intake, blood pressure, participant satisfaction, safety
      measures will also be done.

      The results of the study would help determine the most effective method of increasing
      potassium intake, thus reducing blood pressure, need for blood pressure lowering medicines,
      at the same time potentially increasing participant satisfaction. The current guidelines
      recommend changes in diet (not supplement) to increase potassium intake, hence the two stage
      design will only add supplements if the most rigorous dietary advice does not work. The
      Investigators have received letters of support from the World Hypertension League and
      Hypertension Canada in support of the research design and for dissemination and
      implementation of the findings.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Successful increase in potassium intake
time frame: 4 weeks
description: As estimated by 24 hour urine results at 4 weeks, achieving a urinary sodium > 90 mmol/day.
measure: Persistence of increase in potassium intake at 52 weeks
time frame: 52 weeks
description: As estimated by comparison of persistence of change in potassium intake (as estimated by 24 hour urine results) from 4 weeks to 52 weeks.
measure: Hyperkalemia Events
time frame: 4 weeks to 52 weeks
description: Any episodes of hyperkalemia (as defined as a serum potassium greater than the 5.1 mmol/L)
measure: Gastrointestinal Events
time frame: 4 weeks to 52 weeks
description: Gastrointestinal side effects, specifically changes in bowel habits, belching and/or flatulence; abdominal pain or cramps.
arm group label: Dietary Counselling
arm group type: Experimental
description: All enrolled patients will undergo a 1:1 counselling with a registered dietitian (with possible inclusion of family members, as appropriate). The dietitian will undertake an assessment of the comorbidities (e.g. diabetes), dietary intake, dietary habits (e.g. eating out, food preparation, socio-cultural aspects) and provide an individually tailored strategy to increase potassium in the diet. Secondly, on a weekly basis, the dietitian will contact the patient by telephone, or electronically (as preferred by the patient) to reinforce the advice and provide support/advice as necessary.
arm group label: Potassium Citrate Supplement
arm group type: Active Comparator
description: Patients who are not able to successfully increase their potassium intake at 4 weeks with dietary counselling will receive potassium citrate supplements. They will receive oral potassium supplementation in the form of 50 to 100 mmol of potassium citrate (as 25 to 50 ml of the liquid solution).
intervention type: Behavioral
intervention name: Dietary Counselling
description: Individually tailored strategy to increase potassium in the diet.
arm group label: Dietary Counselling
arm group label: Potassium Citrate Supplement
intervention type: Drug
intervention name: Potassium Citrate
description: Dosing of 50 to 100 mmol of potassium citrate per day (as 25 to 50 ml of the liquid solution).
arm group label: Potassium Citrate Supplement
other name: K-Citra
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Swapnil Hiremath, MD MPH
role: Principal Investigator
affiliation: The Ottawa Hospital
last name: Jennifer Biggs, RN
phone: 613-738-8400
phone ext: 82514
email: jbiggs@ohri.ca
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: Canada
responsible party type: Sponsor
mesh term: Hypertension
mesh term: Potassium Citrate
sharing ipd: No