<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/NCT03833089</url>
  </required_header>
  <id_info>
    <org_study_id>3589</org_study_id>
    <nct_id>NCT03833089</nct_id>
  </id_info>
  <brief_title>Targeted Potassium Levels for Prevention of ICD Therapy</brief_title>
  <official_title>Arrhythmia Prevention in High Risk Cardiovascular Patients Using Targeted Potassium Levels</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rigshospitalet, Denmark</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Herlev and Gentofte Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Rigshospitalet, Denmark</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>
      This study evaluates whether a rigorously controlled high-normal level of serum-potassium&#xD;
      (4.5-5.0 mEq/L) using dietary recommendations, potassium supplements and mineralocorticoid&#xD;
      receptor antagonists will results in a lower incidence of cardiac arrhythmias in patients&#xD;
      with an ICD. Patients will be randomized to this treatment or a control arm, where patients&#xD;
      will receive usual guideline recommended follow-up.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There is solid evidence that potassium-sparing drugs increase survival and ameliorates&#xD;
      symptoms in heart failure patients and post-hoc studies have suggested that high-normal&#xD;
      levels of blood potassium levels (p-K) markedly decreases the risk of malignant arrhythmias&#xD;
      in cardiovascular patients.&#xD;
&#xD;
      This trial will randomize patients implanted with implantable cardioverter defibrillators&#xD;
      (ICDs), who remain at high risk of life-threatening cardiac arrhythmias, to a standard&#xD;
      therapy or standard therapy plus a regimen to keep high-normal p-K levels. The study will&#xD;
      enroll 1,000 patients from the outpatient pacemaker clinics at Rigshospitalet and Gentofte&#xD;
      hospital. Using a planned regime to increase p-K using inexpensive drugs and potassium&#xD;
      supplements, the patients enrolled and followed with regular controls as well as continuous&#xD;
      monitoring using existing home monitoring systems over a period of 4 years for the primary&#xD;
      endpoint of appropriate ICD therapy and all cause mortality. Including analysis, the trial&#xD;
      will be running for 5 years&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 1, 2019</start_date>
  <completion_date type="Anticipated">February 5, 2024</completion_date>
  <primary_completion_date type="Anticipated">February 5, 2023</primary_completion_date>
  <phase>Phase 4</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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to first major event defined as a combination of: - first occurence of ECG documented ventricular tachycardia &gt; 125 bpm lasting &gt; 30 seconds - first occurence of any appropriate ICD therapy as documented by the ICD - All cause mortality</measure>
    <time_frame>4 years</time_frame>
    <description>The time period with regards to the Time-to-Event Outcome Measures starts with the randomization of the patient.&#xD;
ECG documented tachycardia from ECGs or ICD interrogations will be obtained from hospitalizations or outpatients clinic visits via electronic records after patient consent. Information of ventricular tachyarrhythmia therapy will be obtained from home monitoring systems or interrogation of the ICD devices during in-clinic visits.&#xD;
Mortality will be obtained from danish electronic hospital files or the danish death registry.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to first incidence of supraventricular arrhythmias as documented by ECG or the ICD</measure>
    <time_frame>4 years</time_frame>
    <description>Any supraventricular tahcycardia documented on ECG, telemetry or as monitored/treated event on the ICD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients experiencing &lt;92 % CRT-pacing for &gt; 2 weeks (only CRT-D patients)</measure>
    <time_frame>4 years</time_frame>
    <description>CRT-D home monitoring systems allow temporal evaluation of percentage of CRT pacing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first hospitalization for heart failure</measure>
    <time_frame>4 years</time_frame>
    <description>Hospitalization with symptoms of heart failure and with a diagnosis of heart failure where treatment with i.v. diuretics was initiated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first hospitalization for cardiac arrhythmias</measure>
    <time_frame>4 years</time_frame>
    <description>Hospitalization were records indicate that supraventricular or ventricular arrhythmias were implicated in the cause of the hospitalization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to hospitalization for electrolyte disturbances or kidney failure</measure>
    <time_frame>4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>First occurrence of appropriate ICD therapy for ventricular tachycardia or ventricular fibrillation irrespective of outcome.</measure>
    <time_frame>4 years</time_frame>
    <description>Ventricular tachy-arrhythmia therapy, which will be obtained from home monitoring systems or interrogation of the ICD devices during in-clinic visits. All ICD therapy is routinely adjudicated as appropriate or in-appropriate by electrophysiologists at the study sites.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first occurence of inappropriate ICD therapy</measure>
    <time_frame>4 years</time_frame>
    <description>Any cause of inappropriate shock including atrial fibrillation, other supraventricular arrhythmias, ICD lead problems etc.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">1000</enrollment>
  <condition>Ventricular Arrhythmias and Cardiac Arrest</condition>
  <condition>Implantable Defibrillator User</condition>
  <condition>Hypokalemia</condition>
  <condition>Hyperkalemia</condition>
  <condition>Ventricular Tachycardia</condition>
  <condition>Atrial Fibrillation</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>ICD recipients in optimal Medical treatment as per guidelines according to their comorbidity</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Targeted serum potassium levels</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ICD recipients recipients in optimal Medical treatment as per guidelines according to their comorbidity. In addition to guideline recommended treatment, this cohort will be treated to increase serum potassium levels to 4.5-5.0 mEq/L.</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Targeted serum potassium level</intervention_name>
    <description>In the following order, following advices end prescriptions will be provided: 1) Potassium rich dietary advice, 2) Potassium supplementation, 3) mineralocorticoid receptor antagonists,</description>
    <arm_group_label>Targeted serum potassium levels</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Implantable cardioverter defibrillator (ICD) or cardiac resynchronization pacemaker&#xD;
             with ICD (CRT-D).&#xD;
&#xD;
          -  Age &gt;18 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Estimated glomerular filtration rate (eGFR) &lt;30 ml/h&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Lack of ability to understand and sign informed consent&#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>Christian Joens, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dept of Cardiology, Rigshospitalet, Denmark</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Niels Risum, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Dept of Cardiology, Rigshospitalet, Denmark</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Henning Bundgaard, Prof., DMSc</last_name>
    <role>Study Chair</role>
    <affiliation>Dept of Cardiology, Rigshospitalet, Denmark</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Christian Joens, MD, PhD</last_name>
    <phone>+1-647-562-6151</phone>
    <email>Christian.joens.02@regionh.dk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Niels Risum, MD, PhD</last_name>
    <phone>+4523456073</phone>
    <email>niels.risum.01@regionh.dk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Gentofte University Hospital</name>
      <address>
        <city>Gentofte</city>
        <state>Hellerup</state>
        <zip>2900</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tommi B Lindhart, MD, PhD</last_name>
      <phone>38672276</phone>
      <email>tommi.bo.lindhart@regionh.dk</email>
    </contact>
    <contact_backup>
      <last_name>Kasper K Iversen, MD, DMSc</last_name>
      <phone>+4538686009</phone>
      <email>Kasper.karmark.iversen@regionh.dk</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Rigshospitalet</name>
      <address>
        <city>Copenhagen</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christian Joens, MD</last_name>
      <phone>+4535459863</phone>
      <email>christian.joens.02@regionh.dk</email>
    </contact>
    <contact_backup>
      <last_name>Henning Bundgaard, Professor</last_name>
      <phone>+35450512</phone>
      <email>henning.bundgaard@regionh.dk</email>
    </contact_backup>
    <investigator>
      <last_name>Niels Risum, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ulrik Winsloew, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>February 1, 2019</study_first_submitted>
  <study_first_submitted_qc>February 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 6, 2019</study_first_posted>
  <last_update_submitted>October 14, 2021</last_update_submitted>
  <last_update_submitted_qc>October 14, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 15, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Rigshospitalet, Denmark</investigator_affiliation>
    <investigator_full_name>Christian Joens</investigator_full_name>
    <investigator_title>Staff Cardiologist, Electrophysiology, Principal investigator, PhD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</mesh_term>
    <mesh_term>Arrhythmias, Cardiac</mesh_term>
    <mesh_term>Tachycardia</mesh_term>
    <mesh_term>Tachycardia, Ventricular</mesh_term>
    <mesh_term>Hyperkalemia</mesh_term>
    <mesh_term>Hypokalemia</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 4, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/89/NCT03833089/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03833089
org study id: 3589
nct id: NCT03833089
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study evaluates whether a rigorously controlled high-normal level of serum-potassium
      (4.5-5.0 mEq/L) using dietary recommendations, potassium supplements and mineralocorticoid
      receptor antagonists will results in a lower incidence of cardiac arrhythmias in patients
      with an ICD. Patients will be randomized to this treatment or a control arm, where patients
      will receive usual guideline recommended follow-up.
There is solid evidence that potassium-sparing drugs increase survival and ameliorates
      symptoms in heart failure patients and post-hoc studies have suggested that high-normal
      levels of blood potassium levels (p-K) markedly decreases the risk of malignant arrhythmias
      in cardiovascular patients.

      This trial will randomize patients implanted with implantable cardioverter defibrillators
      (ICDs), who remain at high risk of life-threatening cardiac arrhythmias, to a standard
      therapy or standard therapy plus a regimen to keep high-normal p-K levels. The study will
      enroll 1,000 patients from the outpatient pacemaker clinics at Rigshospitalet and Gentofte
      hospital. Using a planned regime to increase p-K using inexpensive drugs and potassium
      supplements, the patients enrolled and followed with regular controls as well as continuous
      monitoring using existing home monitoring systems over a period of 4 years for the primary
      endpoint of appropriate ICD therapy and all cause mortality. Including analysis, the trial
      will be running for 5 years
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Time to first major event defined as a combination of: - first occurence of ECG documented ventricular tachycardia > 125 bpm lasting > 30 seconds - first occurence of any appropriate ICD therapy as documented by the ICD - All cause mortality
time frame: 4 years
description: The time period with regards to the Time-to-Event Outcome Measures starts with the randomization of the patient.
ECG documented tachycardia from ECGs or ICD interrogations will be obtained from hospitalizations or outpatients clinic visits via electronic records after patient consent. Information of ventricular tachyarrhythmia therapy will be obtained from home monitoring systems or interrogation of the ICD devices during in-clinic visits.
Mortality will be obtained from danish electronic hospital files or the danish death registry.
measure: Time to first incidence of supraventricular arrhythmias as documented by ECG or the ICD
time frame: 4 years
description: Any supraventricular tahcycardia documented on ECG, telemetry or as monitored/treated event on the ICD
measure: Proportion of patients experiencing <92 % CRT-pacing for > 2 weeks (only CRT-D patients)
time frame: 4 years
description: CRT-D home monitoring systems allow temporal evaluation of percentage of CRT pacing.
measure: Time to first hospitalization for heart failure
time frame: 4 years
description: Hospitalization with symptoms of heart failure and with a diagnosis of heart failure where treatment with i.v. diuretics was initiated.
measure: Time to first hospitalization for cardiac arrhythmias
time frame: 4 years
description: Hospitalization were records indicate that supraventricular or ventricular arrhythmias were implicated in the cause of the hospitalization
measure: Time to hospitalization for electrolyte disturbances or kidney failure
time frame: 4 years
measure: First occurrence of appropriate ICD therapy for ventricular tachycardia or ventricular fibrillation irrespective of outcome.
time frame: 4 years
description: Ventricular tachy-arrhythmia therapy, which will be obtained from home monitoring systems or interrogation of the ICD devices during in-clinic visits. All ICD therapy is routinely adjudicated as appropriate or in-appropriate by electrophysiologists at the study sites.
measure: Time to first occurence of inappropriate ICD therapy
time frame: 4 years
description: Any cause of inappropriate shock including atrial fibrillation, other supraventricular arrhythmias, ICD lead problems etc.
arm group label: Control
arm group type: No Intervention
description: ICD recipients in optimal Medical treatment as per guidelines according to their comorbidity
arm group label: Targeted serum potassium levels
arm group type: Experimental
description: ICD recipients recipients in optimal Medical treatment as per guidelines according to their comorbidity. In addition to guideline recommended treatment, this cohort will be treated to increase serum potassium levels to 4.5-5.0 mEq/L.
intervention type: Combination Product
intervention name: Targeted serum potassium level
description: In the following order, following advices end prescriptions will be provided: 1) Potassium rich dietary advice, 2) Potassium supplementation, 3) mineralocorticoid receptor antagonists,
arm group label: Targeted serum potassium levels
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Christian Joens, MD, PhD
role: Principal Investigator
affiliation: Dept of Cardiology, Rigshospitalet, Denmark
last name: Niels Risum, MD, PhD
role: Study Chair
affiliation: Dept of Cardiology, Rigshospitalet, Denmark
last name: Henning Bundgaard, Prof., DMSc
role: Study Chair
affiliation: Dept of Cardiology, Rigshospitalet, Denmark
last name: Christian Joens, MD, PhD
phone: +1-647-562-6151
email: Christian.joens.02@regionh.dk
last name: Niels Risum, MD, PhD
phone: +4523456073
email: niels.risum.01@regionh.dk
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: Rigshospitalet, Denmark
investigator full name: Christian Joens
investigator title: Staff Cardiologist, Electrophysiology, Principal investigator, PhD
mesh term: Atrial Fibrillation
mesh term: Arrhythmias, Cardiac
mesh term: Tachycardia
mesh term: Tachycardia, Ventricular
mesh term: Hyperkalemia
mesh term: Hypokalemia
provided document: 