<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/NCT03228823</url>
  </required_header>
  <id_info>
    <org_study_id>NIH ID 9372611</org_study_id>
    <secondary_id>R34HL138110-01</secondary_id>
    <nct_id>NCT03228823</nct_id>
  </id_info>
  <brief_title>Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)</brief_title>
  <acronym>PAPS</acronym>
  <official_title>Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS): A Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hunter Holmes Mcguire Veteran Affairs Medical Center</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Virginia Commonwealth University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Calgary</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Wake Forest University Health Sciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Hunter Holmes Mcguire Veteran Affairs Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Premature ventricular contractions (PVCs) coexist in patients with heart failure (HF) and LV&#xD;
      dysfunction. Frequent PVCs have shown to induce a reversible cardiomyopathy (PVC-CM).&#xD;
&#xD;
      This clinical pilot study will enroll 36 patients with frequent PVCs (burden &gt;10%) and CM&#xD;
      (LVEF &lt;45%) and randomize them to either: 1) RFA or 2) AADs. Prior to treatment, patients&#xD;
      will undergo a baseline cardiac MR if clinically indicated followed by 3-month observation&#xD;
      period (optimal HF medical therapy). Changes in LV function/scar, PVC burden/arrhythmias and&#xD;
      clinical/functional status (QOL, HF symptoms and admissions, NYHA class) and adverse events&#xD;
      will be assessed throughout the observation period and compare with PVC suppression&#xD;
      strategies (RFA or AAD). Similar comparison will be made between RFA and AAD treatment groups&#xD;
      during a 12-month follow up using a Prospective Randomized Open, Blinded End-point (PROBE)&#xD;
      study design. The treatment regimens will be compared in an intention-to-treat analysis. In&#xD;
      addition, a total of 20,000 consecutive ambulatory ECG Holter monitors from all participating&#xD;
      centers will be screened to identify all patients with probable diagnosis of PVC-CM.&#xD;
&#xD;
      This pilot study is intended to estimate the prevalence of this clinical entity and pave the&#xD;
      way for a large full scale randomized trial to identify best treatment strategy for patients&#xD;
      with PVC-CM. Treating and reversing this underestimated PVC-CM may improve patient's health&#xD;
      and subsequently decrease HF healthcare spending.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rationale. Frequent PVCs have shown to induce a reversible cardiomyopathy (PVC-CM). Yet, it&#xD;
      is unclear why some patients develop PVC-CM, while others do not. Appropriate diagnosis and&#xD;
      treatment of patients with PVC-CM is believed to carry significant benefits, improving&#xD;
      quality of life (QOL), HF symptoms / admissions and life expectancy. Currently, these&#xD;
      patients are offered radiofrequency ablation (RFA), antiarrhythmic drugs (AADs) or no&#xD;
      treatment depending on physician's experience and resources. Nevertheless, no&#xD;
      randomized-prospective study exists to support the benefit of RFA. Thus, a large-scale&#xD;
      multicenter randomized clinical trial entitled &quot;Prospective Assessment of PVC Suppression in&#xD;
      Cardiomyopathy (PAPS)&quot;' study has been planned to compare these treatment strategies.&#xD;
      However, a PAPS pilot study is proposed to better estimate the potential affected patient&#xD;
      population, limitations of enrollment, rate of clinical outcomes, potential crossover and&#xD;
      drop out. This pilot study is key to better design and power the large-scale multicenter PAPS&#xD;
      trial.&#xD;
&#xD;
      Objective. PAPS pilot study is a randomized clinical trial to assess the feasibility of&#xD;
      enrolling, randomizing treatment strategies and retaining participants with frequent PVCs and&#xD;
      associated CM.&#xD;
&#xD;
      Hypotheses. Our main hypotheses of the PAPS pilot study are:&#xD;
&#xD;
        1. A large-scale randomized PAPS clinical study is feasible with minimal barriers of&#xD;
           enrollment, treatment crossover and drop out due to a unique design including a short&#xD;
           observation period and PVC suppression strategy in all participants.&#xD;
&#xD;
        2. The rate of responders (defined as improvement of LVEF ≥ 10% points) with HF medical&#xD;
           therapy alone during observation period will be less than 15%. In contrast, RFA and AADs&#xD;
           will have a responder rate of at least 35% in the same population. Furthermore, RFA will&#xD;
           have a greater 1-year response rate when compared to AAD therapy.&#xD;
&#xD;
        3. RFA will have a lower rate of composite adverse events (worsening NYHA class, HF&#xD;
           admission, treatment side effects &amp; complications, and death), arrhythmia burden and a&#xD;
           better long-term tolerance than AADs.&#xD;
&#xD;
      Methods. A prospective clinical pilot study is planned to prove the feasibility of a&#xD;
      large-scale multicenter clinical trial (PAPS study) of patients with probable PVC-CM. This&#xD;
      pilot study will enroll 36 patients with frequent PVCs (burden ≥10%) and CM (LVEF ≤45%) and&#xD;
      randomize them to either: 1) RFA or 2) AADs. Prior to treatment, all patients will undergo a&#xD;
      baseline cardiac MR if clinically indicated and be allowed a 3-month observation period&#xD;
      (optimal HF medical therapy). To assess the effects of PVC suppression, changes in LV&#xD;
      function, rate of responders (defined above), PVC burden/arrhythmias and clinical/functional&#xD;
      status (QOL, HF symptoms and admissions, NYHA class) and adverse events will be compared&#xD;
      between observation period and both PVC suppression strategies (RFA or AAD). To identify the&#xD;
      best PVC suppression strategy, similar comparisons between RFA and AAD treatment groups will&#xD;
      be performed at 12-month follow up using a Prospective Randomized Open, Blinded End-point&#xD;
      (PROBE) study design. The treatment regimens will be compared in an intention-to-treat&#xD;
      analysis.&#xD;
&#xD;
      In summary, the multicenter PAPS pilot study is intended to better estimate the prevalence of&#xD;
      PVC-CM, prove feasibility and rates of clinical outcomes. This pilot study with a&#xD;
      multidisciplinary approach will pave the way for a large-scale randomized PAPS trial to&#xD;
      identify the best treatment strategy for patients with PVC-CM. Treating and reversing PVC-CM&#xD;
      with its associated HF morbidity and mortality will impact not only healthcare spending, but&#xD;
      most importantly it will improve patient's health, quality of life and long-term prognosis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">August 1, 2018</start_date>
  <completion_date type="Anticipated">August 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2021</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>
    <intervention_model_description>PVC suppression with either antiarrhythmic drugs or radiofrequency ablation</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Improvement of left ventricular ejection fraction after PVC suppression</measure>
    <time_frame>12 months</time_frame>
    <description>Compare the overall improvement or change in LVEF between RFA and AAD groups.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Responders to PVC suppression strategy</measure>
    <time_frame>12 months</time_frame>
    <description>Assessment of the number of responders (delta LVEF ≥ 10%) after PVC suppression strategies will assess the effectiveness of RFA and AADs to reverse or improve cardiomyopathy induced by frequent PVCs.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Successful PVC suppression</measure>
    <time_frame>12 months</time_frame>
    <description>Efficacy of Radiofrequency ablation vs. Antiarrhythmic drugs to achieve successful PVC suppression (defined as a reduction of PVC burden greater than ≥80%).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite Adverse Events</measure>
    <time_frame>12 months</time_frame>
    <description>Composite end-point of adverse events, including worsening in NYHA functional class (I-IV), number of HF and cardiac-related admissions, RFA complications and AAD adverse effects and cardiovascular death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite Arrhythmia Burden</measure>
    <time_frame>12 months</time_frame>
    <description>Composite end-point of arrhythmia burden, including PVC recurrence, non-sustained (&lt; 30sec) and sustained (&gt; 30sec) ventricular arrhythmias and arrhythmic sudden cardiac death</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">5</enrollment>
  <condition>Ventricular Premature Beats, Contractions, or Systoles</condition>
  <condition>Cardiomyopathies</condition>
  <arm_group>
    <arm_group_label>Radiofrequency Ablation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Radiofrequency ablation (RFA) will be performed after 3-month observation period. EPS and RFA will be performed using standard techniques and protocols similar to those patients that do not participate in this clinical study. In the event of polymorphic PVCs, all morphologies are to be targeted for ablation</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Antiarrhythmic Drug</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Antiarrhythmic drugs (AADs) will be only initiated after 3-month observation period. AAD therapy of choice is amiodarone. Amiodarone loading dose of 10 grams is recommended, followed by maintenance dose of 200-400mg daily to achieve successful PVC suppression. Investigators define successful PVC suppression only if ≥ 80% absolute reduction in PVC burden is achieved after a drug or intervention. Alternatively, sotalol and/or propafenone could be considered at discretion of electrophysiologists (sotalol dose of at least 120mg twice daily, propafenone 150-300mg tid) if there is a significant concern of safety profile of amiodarone.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Radiofrequency ablation</intervention_name>
    <description>RFA to achieve PVC suppression will be performed using standard techniques and protocols similar to those patients that do not participate in this clinical study.</description>
    <arm_group_label>Radiofrequency Ablation</arm_group_label>
    <other_name>Ablation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Amiodarone (Antiarrhythmic drug)</intervention_name>
    <description>AAD therapy of choice is amiodarone. Amiodarone loading dose of 10 grams is recommended, followed by maintenance dose of 200-400mg daily to achieve successful PVC suppression. Alternatively, sotalol and/or propafenone could be considered at discretion of electrophysiologists (sotalol dose of at least 120mg twice daily, propafenone 150-300mg tid) if there is a significant concern of safety profile of amiodarone.</description>
    <arm_group_label>Antiarrhythmic Drug</arm_group_label>
    <other_name>Amiodarone</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  LV dysfunction (calculated LVEF &lt; or equal to45% based on Echo) within 150 days of&#xD;
             Enrollment (Day 0)&#xD;
&#xD;
          -  PVC burden &gt; or equal to 10% by at least a 24-hr ambulatory Holter monitor (within 150&#xD;
             days of Enrollment (Day 0)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &lt; 18 years old&#xD;
&#xD;
          -  Current amiodarone use or within last 2 months&#xD;
&#xD;
          -  Current use of antiarrhythmic drugs class I or III&#xD;
&#xD;
          -  Contraindication to amiodarone use or any other class III antiarrhythmic&#xD;
&#xD;
          -  Severely symptomatic PVCs (unable to complete 3-month observation period)&#xD;
&#xD;
          -  Severe/significant CAD with planned revascularization in the near future&#xD;
&#xD;
          -  Complete AV block and pacemaker dependent&#xD;
&#xD;
          -  Pacemaker or ICD with &gt;10% RV pacing&#xD;
&#xD;
          -  Severe valvular heart disease or planned valvular/cardiac surgery&#xD;
&#xD;
          -  Uncontrolled / untreated endocrinopathies&#xD;
&#xD;
          -  Uncontrolled HTN, (systolic BP &gt;180mmHg or diastolic &gt;110 mmHg)&#xD;
&#xD;
          -  Hypertrophic cardiomyopathy&#xD;
&#xD;
          -  Systemic infiltrative and immune disorders&#xD;
&#xD;
          -  Family history of dilated CM in a first degree relative&#xD;
&#xD;
          -  Alcohol abuse or illicit drug use&#xD;
&#xD;
          -  Contraindication to short-term acute anticoagulation (due to possible randomization to&#xD;
             ablation)&#xD;
&#xD;
          -  Atrial fibrillation and flutter with rapid ventricular response with possible&#xD;
             tachycardia-induced cardiomyopathy&#xD;
&#xD;
          -  Possible infectious etiology of cardiomyopathy&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Previous PVC ablation&#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>Jose F Huizar, M.D.</last_name>
    <role>Study Director</role>
    <affiliation>McGuire VA Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California Los Angeles Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>James A. Haley Veterans' Hospital</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rush University Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roxbury VA Medical Center</name>
      <address>
        <city>West Roxbury</city>
        <state>Massachusetts</state>
        <zip>02132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwell Health System-Staten Island University Hospital</name>
      <address>
        <city>Staten Island</city>
        <state>New York</state>
        <zip>10305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania Medical Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Virginia</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22908</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McGuire VA Medical Center</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23249</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Commonwealth University</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Libin Cardiovascular Institute, University of Calgary</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 2T9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>July 18, 2017</study_first_submitted>
  <study_first_submitted_qc>July 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 25, 2017</study_first_posted>
  <last_update_submitted>April 13, 2021</last_update_submitted>
  <last_update_submitted_qc>April 13, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 14, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hunter Holmes Mcguire Veteran Affairs Medical Center</investigator_affiliation>
    <investigator_full_name>Jose Huizar</investigator_full_name>
    <investigator_title>Director, Arrhythmia and Device Clinic</investigator_title>
  </responsible_party>
  <keyword>Premature Ventricular contractions</keyword>
  <keyword>Cardiomyopathy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Premature Birth</mesh_term>
    <mesh_term>Cardiomyopathies</mesh_term>
    <mesh_term>Ventricular Premature Complexes</mesh_term>
    <mesh_term>Cardiac Complexes, Premature</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amiodarone</mesh_term>
    <mesh_term>Anti-Arrhythmia Agents</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>This is solely a pilot study of frequent PVCs and cardiomyopathy. Results of this preliminary data will not provide final definitive data, yet investigators will make it available. However, investigators will make clear that this pilot data is not intended to answer benefits of different PVC suppression strategies to avoid misinterpretation or inaccurate conclusions based solely on preliminary data.</ipd_description>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>3-6 months after pilot study has been completed</ipd_time_frame>
  </patient_data>
  <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>April 22, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/23/NCT03228823/Prot_SAP_002.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 28, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/23/NCT03228823/ICF_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/NCT03228823
org study id: NIH ID 9372611
secondary id: R34HL138110-01
nct id: NCT03228823
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Premature ventricular contractions (PVCs) coexist in patients with heart failure (HF) and LV
      dysfunction. Frequent PVCs have shown to induce a reversible cardiomyopathy (PVC-CM).

      This clinical pilot study will enroll 36 patients with frequent PVCs (burden >10%) and CM
      (LVEF <45%) and randomize them to either: 1) RFA or 2) AADs. Prior to treatment, patients
      will undergo a baseline cardiac MR if clinically indicated followed by 3-month observation
      period (optimal HF medical therapy). Changes in LV function/scar, PVC burden/arrhythmias and
      clinical/functional status (QOL, HF symptoms and admissions, NYHA class) and adverse events
      will be assessed throughout the observation period and compare with PVC suppression
      strategies (RFA or AAD). Similar comparison will be made between RFA and AAD treatment groups
      during a 12-month follow up using a Prospective Randomized Open, Blinded End-point (PROBE)
      study design. The treatment regimens will be compared in an intention-to-treat analysis. In
      addition, a total of 20,000 consecutive ambulatory ECG Holter monitors from all participating
      centers will be screened to identify all patients with probable diagnosis of PVC-CM.

      This pilot study is intended to estimate the prevalence of this clinical entity and pave the
      way for a large full scale randomized trial to identify best treatment strategy for patients
      with PVC-CM. Treating and reversing this underestimated PVC-CM may improve patient's health
      and subsequently decrease HF healthcare spending.
Rationale. Frequent PVCs have shown to induce a reversible cardiomyopathy (PVC-CM). Yet, it
      is unclear why some patients develop PVC-CM, while others do not. Appropriate diagnosis and
      treatment of patients with PVC-CM is believed to carry significant benefits, improving
      quality of life (QOL), HF symptoms / admissions and life expectancy. Currently, these
      patients are offered radiofrequency ablation (RFA), antiarrhythmic drugs (AADs) or no
      treatment depending on physician's experience and resources. Nevertheless, no
      randomized-prospective study exists to support the benefit of RFA. Thus, a large-scale
      multicenter randomized clinical trial entitled "Prospective Assessment of PVC Suppression in
      Cardiomyopathy (PAPS)"' study has been planned to compare these treatment strategies.
      However, a PAPS pilot study is proposed to better estimate the potential affected patient
      population, limitations of enrollment, rate of clinical outcomes, potential crossover and
      drop out. This pilot study is key to better design and power the large-scale multicenter PAPS
      trial.

      Objective. PAPS pilot study is a randomized clinical trial to assess the feasibility of
      enrolling, randomizing treatment strategies and retaining participants with frequent PVCs and
      associated CM.

      Hypotheses. Our main hypotheses of the PAPS pilot study are:

        1. A large-scale randomized PAPS clinical study is feasible with minimal barriers of
           enrollment, treatment crossover and drop out due to a unique design including a short
           observation period and PVC suppression strategy in all participants.

        2. The rate of responders (defined as improvement of LVEF ≥ 10% points) with HF medical
           therapy alone during observation period will be less than 15%. In contrast, RFA and AADs
           will have a responder rate of at least 35% in the same population. Furthermore, RFA will
           have a greater 1-year response rate when compared to AAD therapy.

        3. RFA will have a lower rate of composite adverse events (worsening NYHA class, HF
           admission, treatment side effects & complications, and death), arrhythmia burden and a
           better long-term tolerance than AADs.

      Methods. A prospective clinical pilot study is planned to prove the feasibility of a
      large-scale multicenter clinical trial (PAPS study) of patients with probable PVC-CM. This
      pilot study will enroll 36 patients with frequent PVCs (burden ≥10%) and CM (LVEF ≤45%) and
      randomize them to either: 1) RFA or 2) AADs. Prior to treatment, all patients will undergo a
      baseline cardiac MR if clinically indicated and be allowed a 3-month observation period
      (optimal HF medical therapy). To assess the effects of PVC suppression, changes in LV
      function, rate of responders (defined above), PVC burden/arrhythmias and clinical/functional
      status (QOL, HF symptoms and admissions, NYHA class) and adverse events will be compared
      between observation period and both PVC suppression strategies (RFA or AAD). To identify the
      best PVC suppression strategy, similar comparisons between RFA and AAD treatment groups will
      be performed at 12-month follow up using a Prospective Randomized Open, Blinded End-point
      (PROBE) study design. The treatment regimens will be compared in an intention-to-treat
      analysis.

      In summary, the multicenter PAPS pilot study is intended to better estimate the prevalence of
      PVC-CM, prove feasibility and rates of clinical outcomes. This pilot study with a
      multidisciplinary approach will pave the way for a large-scale randomized PAPS trial to
      identify the best treatment strategy for patients with PVC-CM. Treating and reversing PVC-CM
      with its associated HF morbidity and mortality will impact not only healthcare spending, but
      most importantly it will improve patient's health, quality of life and long-term prognosis.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: PVC suppression with either antiarrhythmic drugs or radiofrequency ablation
primary purpose: Treatment
masking: None (Open Label)
measure: Improvement of left ventricular ejection fraction after PVC suppression
time frame: 12 months
description: Compare the overall improvement or change in LVEF between RFA and AAD groups.
measure: Responders to PVC suppression strategy
time frame: 12 months
description: Assessment of the number of responders (delta LVEF ≥ 10%) after PVC suppression strategies will assess the effectiveness of RFA and AADs to reverse or improve cardiomyopathy induced by frequent PVCs.
measure: Successful PVC suppression
time frame: 12 months
description: Efficacy of Radiofrequency ablation vs. Antiarrhythmic drugs to achieve successful PVC suppression (defined as a reduction of PVC burden greater than ≥80%).
measure: Composite Adverse Events
time frame: 12 months
description: Composite end-point of adverse events, including worsening in NYHA functional class (I-IV), number of HF and cardiac-related admissions, RFA complications and AAD adverse effects and cardiovascular death.
measure: Composite Arrhythmia Burden
time frame: 12 months
description: Composite end-point of arrhythmia burden, including PVC recurrence, non-sustained (< 30sec) and sustained (> 30sec) ventricular arrhythmias and arrhythmic sudden cardiac death
arm group label: Radiofrequency Ablation
arm group type: Active Comparator
description: Radiofrequency ablation (RFA) will be performed after 3-month observation period. EPS and RFA will be performed using standard techniques and protocols similar to those patients that do not participate in this clinical study. In the event of polymorphic PVCs, all morphologies are to be targeted for ablation
arm group label: Antiarrhythmic Drug
arm group type: Active Comparator
description: Antiarrhythmic drugs (AADs) will be only initiated after 3-month observation period. AAD therapy of choice is amiodarone. Amiodarone loading dose of 10 grams is recommended, followed by maintenance dose of 200-400mg daily to achieve successful PVC suppression. Investigators define successful PVC suppression only if ≥ 80% absolute reduction in PVC burden is achieved after a drug or intervention. Alternatively, sotalol and/or propafenone could be considered at discretion of electrophysiologists (sotalol dose of at least 120mg twice daily, propafenone 150-300mg tid) if there is a significant concern of safety profile of amiodarone.
intervention type: Procedure
intervention name: Radiofrequency ablation
description: RFA to achieve PVC suppression will be performed using standard techniques and protocols similar to those patients that do not participate in this clinical study.
arm group label: Radiofrequency Ablation
other name: Ablation
intervention type: Drug
intervention name: Amiodarone (Antiarrhythmic drug)
description: AAD therapy of choice is amiodarone. Amiodarone loading dose of 10 grams is recommended, followed by maintenance dose of 200-400mg daily to achieve successful PVC suppression. Alternatively, sotalol and/or propafenone could be considered at discretion of electrophysiologists (sotalol dose of at least 120mg twice daily, propafenone 150-300mg tid) if there is a significant concern of safety profile of amiodarone.
arm group label: Antiarrhythmic Drug
other name: Amiodarone
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jose F Huizar, M.D.
role: Study Director
affiliation: McGuire VA Medical Center
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country: Canada
country: United States
responsible party type: Principal Investigator
investigator affiliation: Hunter Holmes Mcguire Veteran Affairs Medical Center
investigator full name: Jose Huizar
investigator title: Director, Arrhythmia and Device Clinic
mesh term: Premature Birth
mesh term: Cardiomyopathies
mesh term: Ventricular Premature Complexes
mesh term: Cardiac Complexes, Premature
mesh term: Amiodarone
mesh term: Anti-Arrhythmia Agents
sharing ipd: Yes
ipd description: This is solely a pilot study of frequent PVCs and cardiomyopathy. Results of this preliminary data will not provide final definitive data, yet investigators will make it available. However, investigators will make clear that this pilot data is not intended to answer benefits of different PVC suppression strategies to avoid misinterpretation or inaccurate conclusions based solely on preliminary data.
ipd info type: Clinical Study Report (CSR)
ipd time frame: 3-6 months after pilot study has been completed
provided document: 
provided document: 