<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/NCT03032965</url>
  </required_header>
  <id_info>
    <org_study_id>HUM00048922</org_study_id>
    <nct_id>NCT03032965</nct_id>
  </id_info>
  <brief_title>Adenosine to Assess Complete Conduction Block During Catheter Ablation of Paroxysmal Atrial Fibrillation</brief_title>
  <official_title>Adenosine Study in Paroxysmal Atrial Fibrillation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Michigan</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine if additional ablation during the first procedure&#xD;
      as the result of the ability to medically induce quiet atrial arrhythmias will improve&#xD;
      clinical outcome in patients with atrial fibrillation thus decreasing the need for additional&#xD;
      ablation procedures.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hypothesis:&#xD;
&#xD;
        1. Adenosine reveals incomplete conduction block due to partial tissue injury/stunning&#xD;
           during catheter ablation of atrial fibrillation.&#xD;
&#xD;
        2. Identification of incomplete conduction block by adenosine improves clinical outcomes&#xD;
           including an increase in efficacy and a decrease in need for repeat procedures after&#xD;
           catheter ablation of atrial fibrillation.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
        1. In patients with paroxysmal Atrial Fibrillation (AF), the prevalence of Pulmonary Vein&#xD;
           (PV) reconnection during adenosine infusion after complete PV isolation using&#xD;
           conventional techniques will be determined.&#xD;
&#xD;
        2. Patients will be randomized to further ablation to achieve complete isolation during&#xD;
           adenosine infusion vs to no further ablation.&#xD;
&#xD;
        3. Primary endpoint of the study will be freedom from any atrial arrhythmias 6 months after&#xD;
           a single ablation procedure in the absence of antiarrhythmic drug therapy.&#xD;
&#xD;
        4. Secondary endpoints will include number of repeat ablation procedures because of&#xD;
           documented recurrence of symptomatic AF or atrial flutter/tachycardia, outcome after 2&#xD;
           ablation procedures; Proportion of patients with AF or atrial flutter/tachycardia&#xD;
           occuring during the first three months post ablation, prevalence of recovery of&#xD;
           conduction into PVs during repeat ablation procedures in both groups, procedure&#xD;
           duration, and incidence of peri-procedural complications including stroke, PV stenosis,&#xD;
           cardiac perforation, atrio-esophageal fistulae, and death.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2011</start_date>
  <completion_date type="Actual">July 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</primary_completion_date>
  <phase>Phase 2</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Freedom From Any Atrial Arrhythmias</measure>
    <time_frame>2- 14 months after Ablation procedure</time_frame>
    <description>Primary endpoint of the study will be number of participants who are free from any atrial arrhythmias after a single ablation procedure in the absence of antiarrhythmic drug therapy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects Who Need Repeat Ablations</measure>
    <time_frame>date of ablation to 6 months after procedure</time_frame>
    <description>Number of participants who had one or more repeat ablation procedures due to documented recurrence of Symptomatic AF or atrial flutter/tachycardia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects With AF or Atrial Flutter/Tachycardia Occurring During the First Three Months Post Ablation</measure>
    <time_frame>first three months post ablation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Pulmonary Veins That Recovered Conduction During Repeat Ablation Procedures in Both Groups</measure>
    <time_frame>post-procedure (6 months)</time_frame>
    <description>Prevalence of recovery of conduction into pulmonary veins during repeat ablation procedures in both groups. This is determined by surgeon assessment using a circular mapping catheter to identify recovery of conduction into the pulmonary veins.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Stroke</measure>
    <time_frame>peri-procedural (0 to 30 days after procedure)</time_frame>
    <description>Number of subjects who develop stroke within 30 days after procedure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Pulmonary Vein Stenosis</measure>
    <time_frame>6 months post-procedure</time_frame>
    <description>Number of subjects who develop Symptomatic pulmonary vein stenosis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Cardiac Perforation</measure>
    <time_frame>within 24 hours</time_frame>
    <description>Number of subjects who develop perforation of heart during ablation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Atrio-esophageal Fistula</measure>
    <time_frame>within 4 weeks</time_frame>
    <description>Number of subjects who develop connection between heart and the esophagus</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Death</measure>
    <time_frame>with 90 days of the procedure</time_frame>
    <description>Number of deaths within 90 days of the procedure.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">131</enrollment>
  <condition>Atrial Fibrillation</condition>
  <arm_group>
    <arm_group_label>Adenosine and Isoproterenol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Isoproterenol</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>This group will not receive adenosine during the procedure.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Adenosine</intervention_name>
    <description>Subject will receive 6-24 mg of intravenous adenosine given rapidly for each PV in order to assess dormant PV conduction.&#xD;
Subjects in this group will also receive isoproterenol to assess inducibility of AF with re-isolation of PVs and targeting non PV sources of AF if necessary.Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate.</description>
    <arm_group_label>Adenosine and Isoproterenol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Isoproterenol</intervention_name>
    <description>Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to&lt;85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.</description>
    <arm_group_label>Adenosine and Isoproterenol</arm_group_label>
    <arm_group_label>Isoproterenol</arm_group_label>
    <other_name>Isuprel</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients &gt;18 and &lt;75 who are able to give informed consent undergoing atrial&#xD;
             fibrillation ablation procedure.&#xD;
&#xD;
          2. Paroxysmal Atrial fibrillation lasting = 7 days which is self-terminating. It is&#xD;
             considered recurrent if two or more episodes occur.&#xD;
&#xD;
          3. Failure or unwilling to take class I or III anti-arrhythmic drugs&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of asthma&#xD;
&#xD;
          2. Patients with severe coronary artery disease, stable/unstable angina, or ongoing&#xD;
             myocardial ischemia&#xD;
&#xD;
          3. Previous cardiac surgery ( excluding CABG and mitral valve surgery)&#xD;
&#xD;
          4. Symptomatic congestive heart failure including but not limited to NYHA III/IV and/or&#xD;
             documented ejection fraction &lt;40% measured by acceptable cardiac testing,&#xD;
&#xD;
          5. Left atrial diameter &gt;55mm&#xD;
&#xD;
          6. Moderate to severe mitral or aortic valve disease&#xD;
&#xD;
          7. Myocardial infarction within three months of enrollment&#xD;
&#xD;
          8. Congenital heart disease where it increases the risk of an ablative procedure&#xD;
&#xD;
          9. Prior ASD/PFO closure with a device using a percutaneous approach&#xD;
&#xD;
         10. Hypertrophic cardiomyopathy (LV wall thickness &gt;1.5mm)&#xD;
&#xD;
         11. Pulmonary Hypertension (mean or systolic PA pressure&gt; 50mmHg on Doppler&#xD;
             echocardiography&#xD;
&#xD;
         12. Any prior ablation of atrial fibrillation&#xD;
&#xD;
         13. Enrollment in any other arrhythmia protocol&#xD;
&#xD;
         14. Any ventricular arrhythmia being treated where the arrhythmia or management may&#xD;
             interfere with this study&#xD;
&#xD;
         15. Active infection or sepsis&#xD;
&#xD;
         16. Any history of cerebrovascular disease including stroke or TIAs&#xD;
&#xD;
         17. Pregnancy or lactation&#xD;
&#xD;
         18. Left atrial thrombus at the time of ablation&#xD;
&#xD;
         19. Untreatable allergy to contrast media&#xD;
&#xD;
         20. Any diagnosis of atrial fibrillation secondary to electrolyte disturbance, thyroid&#xD;
             disease, or any other reversible or non-cardiovascular causes&#xD;
&#xD;
         21. History of blood clotting(bleeding or thrombotic) abnormalities&#xD;
&#xD;
         22. Known sensitivities to heparin or warfarin&#xD;
&#xD;
         23. Severe COPD (defined as FEV1 &lt;1)&#xD;
&#xD;
         24. Severe comorbidity or poor general physical/mental health that, in opinion of the&#xD;
             investigator, will not allow the patient to be a good study candidate (i.e. other&#xD;
             disease processes, mental capacity, substance abuse, shortened life expectancy)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hamid Ghanbari, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>September 1, 2016</study_first_submitted>
  <study_first_submitted_qc>January 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <results_first_submitted>September 28, 2017</results_first_submitted>
  <results_first_submitted_qc>November 15, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">December 13, 2017</results_first_posted>
  <last_update_submitted>November 15, 2017</last_update_submitted>
  <last_update_submitted_qc>November 15, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 13, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Michigan</investigator_affiliation>
    <investigator_full_name>Hamid Ghanbari</investigator_full_name>
    <investigator_title>Assistant Professor of Internal Medicine</investigator_title>
  </responsible_party>
  <keyword>atrial fibrillation</keyword>
  <keyword>ablation</keyword>
  <keyword>adenosine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenosine</mesh_term>
    <mesh_term>Isoproterenol</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Two subjects were not randomized.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Adenosine and Isoproterenol</title>
          <description>Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction.&#xD;
Adenosine: Subject will receive 6-24 mg of intravenous adenosine given rapidly for each PV in order to assess dormant PV conduction.&#xD;
Subjects in this group will also receive isoproterenol to assess inducibility of AF with re-isolation of PVs and targeting non PV sources of AF if necessary.Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate.&#xD;
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to&lt;85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.</description>
        </group>
        <group group_id="P2">
          <title>Isoproterenol</title>
          <description>This group will not receive adenosine during the procedure.&#xD;
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to&lt;85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="61"/>
                <participants group_id="P2" count="68"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="61"/>
                <participants group_id="P2" count="68"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Adenosine and Isoproterenol</title>
          <description>Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction.&#xD;
Adenosine: Subject will receive 6-24 mg of intravenous adenosine given rapidly for each PV in order to assess dormant PV conduction.&#xD;
Subjects in this group will also receive isoproterenol to assess inducibility of AF with re-isolation of PVs and targeting non PV sources of AF if necessary.Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate.&#xD;
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to&lt;85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.</description>
        </group>
        <group group_id="B2">
          <title>Isoproterenol</title>
          <description>This group will not receive adenosine during the procedure.&#xD;
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to&lt;85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="61"/>
            <count group_id="B2" value="68"/>
            <count group_id="B3" value="129"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.7" spread="8.7"/>
                    <measurement group_id="B2" value="58.9" spread="10.7"/>
                    <measurement group_id="B3" value="59.3" spread="13.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="39"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="37"/>
                    <measurement group_id="B2" value="53"/>
                    <measurement group_id="B3" value="90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61"/>
                    <measurement group_id="B2" value="68"/>
                    <measurement group_id="B3" value="129"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Left ventricular ejection fraction</title>
          <units>Percentage</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.7" spread="5.4"/>
                    <measurement group_id="B2" value="59.3" spread="5.6"/>
                    <measurement group_id="B3" value="59.5" spread="7.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>left atrial diameter</title>
          <units>milli meters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="41.0" spread="5.3"/>
                    <measurement group_id="B2" value="41.2" spread="6.4"/>
                    <measurement group_id="B3" value="41.1" spread="8.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hypertension</title>
          <description>Participants with a documented history of hypertension or being treated for hypertension with medications</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Diabetes Mellitus</title>
          <description>participants with a history of diabetes mellitus or current treatment for diabetes</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Obstructive sleep apnea</title>
          <description>participants with a history of obstructive sleep apnea</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Cerebrovascular accident</title>
          <description>participants with a history of cerebrovascular accident</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Repeat procedure</title>
          <description>These are patients who had a previous ablation prior to entering the study</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>CHADS2 Score ( Congestive heart failure, Hypertension, Age &gt; 75 years, Diabetes Mellitus, Stroke</title>
          <description>Each of these five variables is given 1 point for its presence, except stroke is given 2 points. Each individual point is added, so the score ranges possible are 0 to 6 where 0 represents no risk factors and 6 represents highest number of risk factors.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0.8" spread="0.7"/>
                    <measurement group_id="B2" value="0.7" spread="0.7"/>
                    <measurement group_id="B3" value="0.75" spread="0.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Freedom From Any Atrial Arrhythmias</title>
        <description>Primary endpoint of the study will be number of participants who are free from any atrial arrhythmias after a single ablation procedure in the absence of antiarrhythmic drug therapy</description>
        <time_frame>2- 14 months after Ablation procedure</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Adenosine and Isoproterenol</title>
            <description>Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction.&#xD;
Adenosine: Subject will receive 6-24 mg of intravenous adenosine given rapidly for each PV in order to assess dormant PV conduction.&#xD;
Subjects in this group will also receive isoproterenol to assess inducibility of AF with re-isolation of PVs and targeting non PV sources of AF if necessary.Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate.&#xD;
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to&lt;85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.</description>
          </group>
          <group group_id="O2">
            <title>Isoproterenol</title>
            <description>This group will not receive adenosine during the procedure.&#xD;
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to&lt;85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.</description>
          </group>
        </group_list>
        <measure>
          <title>Freedom From Any Atrial Arrhythmias</title>
          <description>Primary endpoint of the study will be number of participants who are free from any atrial arrhythmias after a single ablation procedure in the absence of antiarrhythmic drug therapy</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="61"/>
                <count group_id="O2" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24"/>
                    <measurement group_id="O2" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.83</p_value>
            <method>Log Rank</method>
            <method_desc>Kaplan Meier log rank</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Subjects Who Need Repeat Ablations</title>
        <description>Number of participants who had one or more repeat ablation procedures due to documented recurrence of Symptomatic AF or atrial flutter/tachycardia.</description>
        <time_frame>date of ablation to 6 months after procedure</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Adenosine and Isoproterenol</title>
            <description>Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction.&#xD;
Adenosine: Subject will receive 6-24 mg of intravenous adenosine given rapidly for each PV in order to assess dormant PV conduction.&#xD;
Subjects in this group will also receive isoproterenol to assess inducibility of AF with re-isolation of PVs and targeting non PV sources of AF if necessary.Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate.&#xD;
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to&lt;85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.</description>
          </group>
          <group group_id="O2">
            <title>Isoproterenol</title>
            <description>This group will not receive adenosine during the procedure.&#xD;
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to&lt;85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects Who Need Repeat Ablations</title>
          <description>Number of participants who had one or more repeat ablation procedures due to documented recurrence of Symptomatic AF or atrial flutter/tachycardia.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="61"/>
                <count group_id="O2" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.35</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Subjects With AF or Atrial Flutter/Tachycardia Occurring During the First Three Months Post Ablation</title>
        <time_frame>first three months post ablation</time_frame>
        <population>This data was not collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Adenosine and Isoproterenol</title>
            <description>Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction.&#xD;
Adenosine: Subject will receive 6-24 mg of intravenous adenosine given rapidly for each PV in order to assess dormant PV conduction.&#xD;
Subjects in this group will also receive isoproterenol to assess inducibility of AF with re-isolation of PVs and targeting non PV sources of AF if necessary.Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate.&#xD;
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to&lt;85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.</description>
          </group>
          <group group_id="O2">
            <title>Isoproterenol</title>
            <description>This group will not receive adenosine during the procedure.&#xD;
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to&lt;85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects With AF or Atrial Flutter/Tachycardia Occurring During the First Three Months Post Ablation</title>
          <population>This data was not collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Pulmonary Veins That Recovered Conduction During Repeat Ablation Procedures in Both Groups</title>
        <description>Prevalence of recovery of conduction into pulmonary veins during repeat ablation procedures in both groups. This is determined by surgeon assessment using a circular mapping catheter to identify recovery of conduction into the pulmonary veins.</description>
        <time_frame>post-procedure (6 months)</time_frame>
        <population>Only 21 participants had repeat ablations; each participant has four pulmonary veins therefore the number of connections measured is based 4 x the number of participants</population>
        <group_list>
          <group group_id="O1">
            <title>Adenosine and Isoproterenol</title>
            <description>Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction.&#xD;
Adenosine: Subject will receive 6-24 mg of intravenous adenosine given rapidly for each PV in order to assess dormant PV conduction.&#xD;
Subjects in this group will also receive isoproterenol to assess inducibility of AF with re-isolation of PVs and targeting non PV sources of AF if necessary.Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate.&#xD;
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to&lt;85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.</description>
          </group>
          <group group_id="O2">
            <title>Isoproterenol</title>
            <description>This group will not receive adenosine during the procedure.&#xD;
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to&lt;85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Pulmonary Veins That Recovered Conduction During Repeat Ablation Procedures in Both Groups</title>
          <description>Prevalence of recovery of conduction into pulmonary veins during repeat ablation procedures in both groups. This is determined by surgeon assessment using a circular mapping catheter to identify recovery of conduction into the pulmonary veins.</description>
          <population>Only 21 participants had repeat ablations; each participant has four pulmonary veins therefore the number of connections measured is based 4 x the number of participants</population>
          <units>pulmonary veins</units>
          <param>Count of Units</param>
          <units_analyzed>pulmonary veins</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>pulmonary veins</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="48"/>
                <count group_id="O2" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29"/>
                    <measurement group_id="O2" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.09</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Stroke</title>
        <description>Number of subjects who develop stroke within 30 days after procedure.</description>
        <time_frame>peri-procedural (0 to 30 days after procedure)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Adenosine and Isoproterenol</title>
            <description>Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction.&#xD;
Adenosine: Subject will receive 6-24 mg of intravenous adenosine given rapidly for each PV in order to assess dormant PV conduction.&#xD;
Subjects in this group will also receive isoproterenol to assess inducibility of AF with re-isolation of PVs and targeting non PV sources of AF if necessary.Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate.&#xD;
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to&lt;85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.</description>
          </group>
          <group group_id="O2">
            <title>Isoproterenol</title>
            <description>This group will not receive adenosine during the procedure.&#xD;
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to&lt;85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Stroke</title>
          <description>Number of subjects who develop stroke within 30 days after procedure.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="61"/>
                <count group_id="O2" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Pulmonary Vein Stenosis</title>
        <description>Number of subjects who develop Symptomatic pulmonary vein stenosis</description>
        <time_frame>6 months post-procedure</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Adenosine and Isoproterenol</title>
            <description>Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction.&#xD;
Adenosine: Subject will receive 6-24 mg of intravenous adenosine given rapidly for each PV in order to assess dormant PV conduction.&#xD;
Subjects in this group will also receive isoproterenol to assess inducibility of AF with re-isolation of PVs and targeting non PV sources of AF if necessary.Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate.&#xD;
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to&lt;85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.</description>
          </group>
          <group group_id="O2">
            <title>Isoproterenol</title>
            <description>This group will not receive adenosine during the procedure.&#xD;
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to&lt;85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Pulmonary Vein Stenosis</title>
          <description>Number of subjects who develop Symptomatic pulmonary vein stenosis</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="61"/>
                <count group_id="O2" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Cardiac Perforation</title>
        <description>Number of subjects who develop perforation of heart during ablation</description>
        <time_frame>within 24 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Adenosine and Isoproterenol</title>
            <description>Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction.&#xD;
Adenosine: Subject will receive 6-24 mg of intravenous adenosine given rapidly for each PV in order to assess dormant PV conduction.&#xD;
Subjects in this group will also receive isoproterenol to assess inducibility of AF with re-isolation of PVs and targeting non PV sources of AF if necessary.Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate.&#xD;
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to&lt;85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.</description>
          </group>
          <group group_id="O2">
            <title>Isoproterenol</title>
            <description>This group will not receive adenosine during the procedure.&#xD;
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to&lt;85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Cardiac Perforation</title>
          <description>Number of subjects who develop perforation of heart during ablation</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="61"/>
                <count group_id="O2" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Atrio-esophageal Fistula</title>
        <description>Number of subjects who develop connection between heart and the esophagus</description>
        <time_frame>within 4 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Adenosine and Isoproterenol</title>
            <description>Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction.&#xD;
Adenosine: Subject will receive 6-24 mg of intravenous adenosine given rapidly for each PV in order to assess dormant PV conduction.&#xD;
Subjects in this group will also receive isoproterenol to assess inducibility of AF with re-isolation of PVs and targeting non PV sources of AF if necessary.Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate.&#xD;
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to&lt;85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.</description>
          </group>
          <group group_id="O2">
            <title>Isoproterenol</title>
            <description>This group will not receive adenosine during the procedure.&#xD;
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to&lt;85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Atrio-esophageal Fistula</title>
          <description>Number of subjects who develop connection between heart and the esophagus</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="61"/>
                <count group_id="O2" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Death</title>
        <description>Number of deaths within 90 days of the procedure.</description>
        <time_frame>with 90 days of the procedure</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Adenosine and Isoproterenol</title>
            <description>Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction.&#xD;
Adenosine: Subject will receive 6-24 mg of intravenous adenosine given rapidly for each PV in order to assess dormant PV conduction.&#xD;
Subjects in this group will also receive isoproterenol to assess inducibility of AF with re-isolation of PVs and targeting non PV sources of AF if necessary.Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate.&#xD;
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to&lt;85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.</description>
          </group>
          <group group_id="O2">
            <title>Isoproterenol</title>
            <description>This group will not receive adenosine during the procedure.&#xD;
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to&lt;85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Death</title>
          <description>Number of deaths within 90 days of the procedure.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="61"/>
                <count group_id="O2" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>within 24 hours of procedure</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Adenosine and Isoproterenol</title>
          <description>Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction.&#xD;
Adenosine: Subject will receive 6-24 mg of intravenous adenosine given rapidly for each PV in order to assess dormant PV conduction.&#xD;
Subjects in this group will also receive isoproterenol to assess inducibility of AF with re-isolation of PVs and targeting non PV sources of AF if necessary.Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate.&#xD;
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to&lt;85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.</description>
        </group>
        <group group_id="E2">
          <title>Isoproterenol</title>
          <description>This group will not receive adenosine during the procedure.&#xD;
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to&lt;85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="61"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="61"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Transient phrenic nerve paralysis</sub_title>
                <description>Phrenic nerve paralysis.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="61"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Site hematoma</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <description>Femoral vein/groin hematoma.</description>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="61"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Pericardial Effusion</sub_title>
                <description>Pericardial effusion with hemodynamic compromise.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="61"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>A V Fistula</sub_title>
                <description>Arterio venous fistula between femoral artery and vein.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="61"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="61"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Hamid Ghanbari</name_or_title>
      <organization>University of Michigan</organization>
      <phone>734-963-7141</phone>
      <email>ghhamid@med.umich.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03032965
org study id: HUM00048922
nct id: NCT03032965
lead sponsor: 
has dmc: No
The purpose of this study is to determine if additional ablation during the first procedure
      as the result of the ability to medically induce quiet atrial arrhythmias will improve
      clinical outcome in patients with atrial fibrillation thus decreasing the need for additional
      ablation procedures.
Hypothesis:

        1. Adenosine reveals incomplete conduction block due to partial tissue injury/stunning
           during catheter ablation of atrial fibrillation.

        2. Identification of incomplete conduction block by adenosine improves clinical outcomes
           including an increase in efficacy and a decrease in need for repeat procedures after
           catheter ablation of atrial fibrillation.

      Objectives:

        1. In patients with paroxysmal Atrial Fibrillation (AF), the prevalence of Pulmonary Vein
           (PV) reconnection during adenosine infusion after complete PV isolation using
           conventional techniques will be determined.

        2. Patients will be randomized to further ablation to achieve complete isolation during
           adenosine infusion vs to no further ablation.

        3. Primary endpoint of the study will be freedom from any atrial arrhythmias 6 months after
           a single ablation procedure in the absence of antiarrhythmic drug therapy.

        4. Secondary endpoints will include number of repeat ablation procedures because of
           documented recurrence of symptomatic AF or atrial flutter/tachycardia, outcome after 2
           ablation procedures; Proportion of patients with AF or atrial flutter/tachycardia
           occuring during the first three months post ablation, prevalence of recovery of
           conduction into PVs during repeat ablation procedures in both groups, procedure
           duration, and incidence of peri-procedural complications including stroke, PV stenosis,
           cardiac perforation, atrio-esophageal fistulae, and death.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Freedom From Any Atrial Arrhythmias
time frame: 2- 14 months after Ablation procedure
description: Primary endpoint of the study will be number of participants who are free from any atrial arrhythmias after a single ablation procedure in the absence of antiarrhythmic drug therapy
measure: Number of Subjects Who Need Repeat Ablations
time frame: date of ablation to 6 months after procedure
description: Number of participants who had one or more repeat ablation procedures due to documented recurrence of Symptomatic AF or atrial flutter/tachycardia.
measure: Number of Subjects With AF or Atrial Flutter/Tachycardia Occurring During the First Three Months Post Ablation
time frame: first three months post ablation
measure: Number of Pulmonary Veins That Recovered Conduction During Repeat Ablation Procedures in Both Groups
time frame: post-procedure (6 months)
description: Prevalence of recovery of conduction into pulmonary veins during repeat ablation procedures in both groups. This is determined by surgeon assessment using a circular mapping catheter to identify recovery of conduction into the pulmonary veins.
measure: Incidence of Stroke
time frame: peri-procedural (0 to 30 days after procedure)
description: Number of subjects who develop stroke within 30 days after procedure.
measure: Incidence of Pulmonary Vein Stenosis
time frame: 6 months post-procedure
description: Number of subjects who develop Symptomatic pulmonary vein stenosis
measure: Incidence of Cardiac Perforation
time frame: within 24 hours
description: Number of subjects who develop perforation of heart during ablation
measure: Incidence of Atrio-esophageal Fistula
time frame: within 4 weeks
description: Number of subjects who develop connection between heart and the esophagus
measure: Incidence of Death
time frame: with 90 days of the procedure
description: Number of deaths within 90 days of the procedure.
arm group label: Adenosine and Isoproterenol
arm group type: Experimental
description: Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction.
arm group label: Isoproterenol
arm group type: Other
description: This group will not receive adenosine during the procedure.
intervention type: Drug
intervention name: Adenosine
description: Subject will receive 6-24 mg of intravenous adenosine given rapidly for each PV in order to assess dormant PV conduction.
Subjects in this group will also receive isoproterenol to assess inducibility of AF with re-isolation of PVs and targeting non PV sources of AF if necessary.Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate.
arm group label: Adenosine and Isoproterenol
intervention type: Drug
intervention name: Isoproterenol
description: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to<85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.
arm group label: Adenosine and Isoproterenol
arm group label: Isoproterenol
other name: Isuprel
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Hamid Ghanbari, MD
role: Principal Investigator
affiliation: University of Michigan
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Michigan
investigator full name: Hamid Ghanbari
investigator title: Assistant Professor of Internal Medicine
mesh term: Atrial Fibrillation
mesh term: Adenosine
mesh term: Isoproterenol
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 