<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/NCT04472936</url>
  </required_header>
  <id_info>
    <org_study_id>SIMPLE</org_study_id>
    <nct_id>NCT04472936</nct_id>
  </id_info>
  <brief_title>Long-term outcomeS of cavotrIcuspid isthMus-dePendent fLuttEr Ablation: Single vs Double Catheter Procedure</brief_title>
  <official_title>Long-term outcomeS of cavotrIcuspid isthMus-dePendent fLuttEr Ablation: Randomized Study Comparing Single vs Double Catheter Procedure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centro Medico Teknon</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centro Medico Teknon</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Catheter ablation is recommended as first-line therapy for most patients with typical atrial&#xD;
      flutter. The most common approach is to create an ablation line across the cavotricuspid&#xD;
      isthmus (CTI). Traditionally, atrial flutter ablation has been performed with a conventional&#xD;
      approach using two catheters, an ablation catheter and a duodecapolar catheter that is placed&#xD;
      at the level of the tricuspid annulus to confirm the CTI block. Recently, a single catheter&#xD;
      approach has been described using the behavior of PR interval change during differential&#xD;
      pacing over the ablation line to prove CTI block. This prospective, randomized, multicenter&#xD;
      study analyzes the effectivity of a single catheter approach compared with conventional&#xD;
      approach in terms of clinical outcomes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Typical atrial flutter is a reentrant rhythm in the right atrium that is constrained&#xD;
      anteriorly by the tricuspid annulus and posteriorly by the crista terminalis and eustachian&#xD;
      ridge. Catheter ablation is the first-line therapy for most patients with typical atrial&#xD;
      flutter. The most common approach is to create an ablation line across the CTI, from the&#xD;
      tricuspid annulus to the inferior vena cava. Traditionally, atrial flutter ablation has been&#xD;
      performed with a conventional approach using two catheters, an ablation catheter and a&#xD;
      duodecapolar catheter that is placed at the level of the tricuspid annulus that allows to&#xD;
      evaluate the right atrial activation sequence to confirm the CTI block. Recently, a single&#xD;
      catheter approach has been described using the behavior of PR interval (PRI) change during&#xD;
      differential pacing over the ablation line to prove CTI block. The PRIs is measured for three&#xD;
      different pacing site, 5 o'clock (medial to CTI line), 7 o'clock (lateral to CTI line), and 9&#xD;
      o'clock position. CTI block was assumed when the PRI at 7 o'clock was &gt;80ms longer than that&#xD;
      at pacing sites of 5 o'clock and the PRI at 9 o'clock was shorter than the PRI at 7 o'clock.&#xD;
      However, a direct comparison between this approach and the conventional one was not yet&#xD;
      performed. This prospective, randomized, multicenter study analyzes the effectivity of a&#xD;
      single catheter approach compared with conventional approach in terms of clinical outcomes.&#xD;
      Our research hypothesis is that a single catheter approach has the possible advantages of&#xD;
      being a faster, more efficient and cheaper procedure than the conventional approach.&#xD;
      Moreover, as it only requires a single venous access, the risk of complications is decreased.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 16, 2020</start_date>
  <completion_date type="Actual">November 30, 2022</completion_date>
  <primary_completion_date type="Actual">September 30, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical outcomes</measure>
    <time_frame>6 months</time_frame>
    <description>The recurrence rate of typical atrial flutter at 6 months post cavotricuspid isthmus ablation will be evaluated in both groups to determine if the single catheter approach is non-inferior when compared to traditional approach using two catheters.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficiency in total procedure time</measure>
    <time_frame>6 months</time_frame>
    <description>The total procedure time time will be measured in both groups to determine if the single catheter approach is more efficient procedure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficiency in ablation time</measure>
    <time_frame>6 months</time_frame>
    <description>The ablation time will be measured in both groups to determine if the single catheter approach is more efficient procedure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficiency in fluoroscopy time</measure>
    <time_frame>6 months</time_frame>
    <description>The fluoroscopy time will be measured in both groups to determine if the single catheter approach is more efficient procedure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complications</measure>
    <time_frame>6 months</time_frame>
    <description>We will compare the complication rate of both approaches.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cost-effectiveness</measure>
    <time_frame>6 months</time_frame>
    <description>We will perform a cost-effectiveness analysis.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">253</enrollment>
  <condition>Atrial Flutter</condition>
  <arm_group>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Double venous femoral access will be obtained. A duodecapolar catheter placed around tricuspid annulus will be used to prove isthmus block after CTI ablation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ablation will be performed similar as described in the Group A. After the ablation line is over, PRI on the surface ECG will be used to prove isthmus block after CTI ablation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Single catheter approach</intervention_name>
    <description>Single venous femoral access will be obtained and the ablation will be performed similar to Group A. After the ablation line is over, we will confirm CTI block using the PRI. During atrial pacing (10 V, 1.5 ms) at a stable cycle length (range 500-700ms) from the tip of the ablation catheter with a sweep speed of 300mm/s, the ablation catheter will be placed first at 5 o'clock (medial to CTI line), then at 7 o'clock (lateral to CTI line), and finally at 9 o'clock position, and the corresponding PRIs will be measured for each pacing site. CTI block is assumed when: (i) the PRI at 7 o'clock is &gt;80ms longer than that at pacing sites of 5, and (ii) the PRI at 9 o'clock is shorter than the PRI at 7 o'clock.</description>
    <arm_group_label>Group B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Traditional approach</intervention_name>
    <description>Double venous femoral access will be obtained. A duodecapolar catheter will be positioned in the right atrium around the tricuspid valve annulus (TVA) to record activation sequence around the tricuspid annulus. An ablation catheter will be positioned using fluoroscopic guidance in the central CTI, 6 o'clock in a left anterior oblique view. The distal ablation electrode position will then be adjusted toward or away from the TVA, based on the ratio of atrial and ventricular electrogram amplitudes with an optimal ratio of 1:2 or 1:4 at the TVA. After the ablation catheter is positioned, it will be very slowly withdrawn during ablation toward the inferior vena cava while radiofrequency energy is applied continuously. CTI block will be evaluated after ablation by determining the right atrial activation sequence during pacing from the low lateral right atrium and coronary sinus ostium.</description>
    <arm_group_label>Group A</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients admitted at any of the centers to perform a CTI ablation.&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &lt; 18 years.&#xD;
&#xD;
          -  Pregnancy.&#xD;
&#xD;
          -  Impossibility to perform CTI ablation.&#xD;
&#xD;
          -  Impossibility to measure PRI (complete atrioventricular block).&#xD;
&#xD;
          -  Ablation of other cardiac arrhythmias during the same procedure.&#xD;
&#xD;
          -  Medical, geographical and social factors that make study participation impractical,&#xD;
             and inability to give written informed consent. Patient's refusal to participate in&#xD;
             the study.&#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>Antonio Berruezo, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centro Medico Teknon</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centro Medico Teknon</name>
      <address>
        <city>Barcelona</city>
        <zip>08022</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Puerta del Mar University Hospital</name>
      <address>
        <city>Cadiz</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virgen del Rocio University Hospital</name>
      <address>
        <city>Sevilla</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <reference>
    <citation>Feld GK, Fleck RP, Chen PS, Boyce K, Bahnson TD, Stein JB, Calisi CM, Ibarra M. Radiofrequency catheter ablation for the treatment of human type 1 atrial flutter. Identification of a critical zone in the reentrant circuit by endocardial mapping techniques. Circulation. 1992 Oct;86(4):1233-40. doi: 10.1161/01.cir.86.4.1233.</citation>
    <PMID>1394929</PMID>
  </reference>
  <reference>
    <citation>Cosio FG, Lopez-Gil M, Goicolea A, Arribas F, Barroso JL. Radiofrequency ablation of the inferior vena cava-tricuspid valve isthmus in common atrial flutter. Am J Cardiol. 1993 Mar 15;71(8):705-9. doi: 10.1016/0002-9149(93)91014-9.</citation>
    <PMID>8447269</PMID>
  </reference>
  <reference>
    <citation>Lesh MD, Van Hare GF, Epstein LM, Fitzpatrick AP, Scheinman MM, Lee RJ, Kwasman MA, Grogin HR, Griffin JC. Radiofrequency catheter ablation of atrial arrhythmias. Results and mechanisms. Circulation. 1994 Mar;89(3):1074-89. doi: 10.1161/01.cir.89.3.1074.</citation>
    <PMID>8124793</PMID>
  </reference>
  <reference>
    <citation>Page RL, Joglar JA, Caldwell MA, Calkins H, Conti JB, Deal BJ, Estes NA III, Field ME, Goldberger ZD, Hammill SC, Indik JH, Lindsay BD, Olshansky B, Russo AM, Shen WK, Tracy CM, Al-Khatib SM. 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm. 2016 Apr;13(4):e136-221. doi: 10.1016/j.hrthm.2015.09.019. Epub 2015 Sep 25. No abstract available.</citation>
    <PMID>26409100</PMID>
  </reference>
  <reference>
    <citation>Shah DC, Takahashi A, Jais P, Hocini M, Clementy J, Haissaguerre M. Local electrogram-based criteria of cavotricuspid isthmus block. J Cardiovasc Electrophysiol. 1999 May;10(5):662-9. doi: 10.1111/j.1540-8167.1999.tb00243.x.</citation>
    <PMID>10355922</PMID>
  </reference>
  <reference>
    <citation>Madaffari A, Krisai P, Spies F, Knecht S, Schaer B, Kojic D, Kuhne M, Sticherling C, Osswald S. Ablation of typical atrial flutter guided by the paced PR interval on the surface electrocardiogram: a proof of concept study. Europace. 2019 Nov 1;21(11):1750-1754. doi: 10.1093/europace/euz208.</citation>
    <PMID>31384937</PMID>
  </reference>
  <reference>
    <citation>Calkins H, Canby R, Weiss R, Taylor G, Wells P, Chinitz L, Milstein S, Compton S, Oleson K, Sherfesee L, Onufer J; 100W Atakr II Investigator Group. Results of catheter ablation of typical atrial flutter. Am J Cardiol. 2004 Aug 15;94(4):437-42. doi: 10.1016/j.amjcard.2004.04.058.</citation>
    <PMID>15325925</PMID>
  </reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>June 13, 2020</study_first_submitted>
  <study_first_submitted_qc>July 12, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 16, 2020</study_first_posted>
  <last_update_submitted>August 29, 2023</last_update_submitted>
  <last_update_submitted_qc>August 29, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 30, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Centro Medico Teknon</investigator_affiliation>
    <investigator_full_name>Antonio Berruezo, MD, PhD</investigator_full_name>
    <investigator_title>Research Coordinator of the Heart Institute</investigator_title>
  </responsible_party>
  <keyword>Atrial flutter</keyword>
  <keyword>Catheter ablation</keyword>
  <keyword>Single catheter approach</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Flutter</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04472936
org study id: SIMPLE
nct id: NCT04472936
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Catheter ablation is recommended as first-line therapy for most patients with typical atrial
      flutter. The most common approach is to create an ablation line across the cavotricuspid
      isthmus (CTI). Traditionally, atrial flutter ablation has been performed with a conventional
      approach using two catheters, an ablation catheter and a duodecapolar catheter that is placed
      at the level of the tricuspid annulus to confirm the CTI block. Recently, a single catheter
      approach has been described using the behavior of PR interval change during differential
      pacing over the ablation line to prove CTI block. This prospective, randomized, multicenter
      study analyzes the effectivity of a single catheter approach compared with conventional
      approach in terms of clinical outcomes.
Typical atrial flutter is a reentrant rhythm in the right atrium that is constrained
      anteriorly by the tricuspid annulus and posteriorly by the crista terminalis and eustachian
      ridge. Catheter ablation is the first-line therapy for most patients with typical atrial
      flutter. The most common approach is to create an ablation line across the CTI, from the
      tricuspid annulus to the inferior vena cava. Traditionally, atrial flutter ablation has been
      performed with a conventional approach using two catheters, an ablation catheter and a
      duodecapolar catheter that is placed at the level of the tricuspid annulus that allows to
      evaluate the right atrial activation sequence to confirm the CTI block. Recently, a single
      catheter approach has been described using the behavior of PR interval (PRI) change during
      differential pacing over the ablation line to prove CTI block. The PRIs is measured for three
      different pacing site, 5 o'clock (medial to CTI line), 7 o'clock (lateral to CTI line), and 9
      o'clock position. CTI block was assumed when the PRI at 7 o'clock was >80ms longer than that
      at pacing sites of 5 o'clock and the PRI at 9 o'clock was shorter than the PRI at 7 o'clock.
      However, a direct comparison between this approach and the conventional one was not yet
      performed. This prospective, randomized, multicenter study analyzes the effectivity of a
      single catheter approach compared with conventional approach in terms of clinical outcomes.
      Our research hypothesis is that a single catheter approach has the possible advantages of
      being a faster, more efficient and cheaper procedure than the conventional approach.
      Moreover, as it only requires a single venous access, the risk of complications is decreased.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Clinical outcomes
time frame: 6 months
description: The recurrence rate of typical atrial flutter at 6 months post cavotricuspid isthmus ablation will be evaluated in both groups to determine if the single catheter approach is non-inferior when compared to traditional approach using two catheters.
measure: Efficiency in total procedure time
time frame: 6 months
description: The total procedure time time will be measured in both groups to determine if the single catheter approach is more efficient procedure.
measure: Efficiency in ablation time
time frame: 6 months
description: The ablation time will be measured in both groups to determine if the single catheter approach is more efficient procedure.
measure: Efficiency in fluoroscopy time
time frame: 6 months
description: The fluoroscopy time will be measured in both groups to determine if the single catheter approach is more efficient procedure.
measure: Complications
time frame: 6 months
description: We will compare the complication rate of both approaches.
measure: Cost-effectiveness
time frame: 6 months
description: We will perform a cost-effectiveness analysis.
arm group label: Group A
arm group type: Active Comparator
description: Double venous femoral access will be obtained. A duodecapolar catheter placed around tricuspid annulus will be used to prove isthmus block after CTI ablation.
arm group label: Group B
arm group type: Experimental
description: Ablation will be performed similar as described in the Group A. After the ablation line is over, PRI on the surface ECG will be used to prove isthmus block after CTI ablation.
intervention type: Procedure
intervention name: Single catheter approach
description: Single venous femoral access will be obtained and the ablation will be performed similar to Group A. After the ablation line is over, we will confirm CTI block using the PRI. During atrial pacing (10 V, 1.5 ms) at a stable cycle length (range 500-700ms) from the tip of the ablation catheter with a sweep speed of 300mm/s, the ablation catheter will be placed first at 5 o'clock (medial to CTI line), then at 7 o'clock (lateral to CTI line), and finally at 9 o'clock position, and the corresponding PRIs will be measured for each pacing site. CTI block is assumed when: (i) the PRI at 7 o'clock is >80ms longer than that at pacing sites of 5, and (ii) the PRI at 9 o'clock is shorter than the PRI at 7 o'clock.
arm group label: Group B
intervention type: Procedure
intervention name: Traditional approach
description: Double venous femoral access will be obtained. A duodecapolar catheter will be positioned in the right atrium around the tricuspid valve annulus (TVA) to record activation sequence around the tricuspid annulus. An ablation catheter will be positioned using fluoroscopic guidance in the central CTI, 6 o'clock in a left anterior oblique view. The distal ablation electrode position will then be adjusted toward or away from the TVA, based on the ratio of atrial and ventricular electrogram amplitudes with an optimal ratio of 1:2 or 1:4 at the TVA. After the ablation catheter is positioned, it will be very slowly withdrawn during ablation toward the inferior vena cava while radiofrequency energy is applied continuously. CTI block will be evaluated after ablation by determining the right atrial activation sequence during pacing from the low lateral right atrium and coronary sinus ostium.
arm group label: Group A
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Antonio Berruezo, MD, PhD
role: Principal Investigator
affiliation: Centro Medico Teknon
facility: 
facility: 
facility: 
country: Spain
citation: Feld GK, Fleck RP, Chen PS, Boyce K, Bahnson TD, Stein JB, Calisi CM, Ibarra M. Radiofrequency catheter ablation for the treatment of human type 1 atrial flutter. Identification of a critical zone in the reentrant circuit by endocardial mapping techniques. Circulation. 1992 Oct;86(4):1233-40. doi: 10.1161/01.cir.86.4.1233.
PMID: 1394929
citation: Cosio FG, Lopez-Gil M, Goicolea A, Arribas F, Barroso JL. Radiofrequency ablation of the inferior vena cava-tricuspid valve isthmus in common atrial flutter. Am J Cardiol. 1993 Mar 15;71(8):705-9. doi: 10.1016/0002-9149(93)91014-9.
PMID: 8447269
citation: Lesh MD, Van Hare GF, Epstein LM, Fitzpatrick AP, Scheinman MM, Lee RJ, Kwasman MA, Grogin HR, Griffin JC. Radiofrequency catheter ablation of atrial arrhythmias. Results and mechanisms. Circulation. 1994 Mar;89(3):1074-89. doi: 10.1161/01.cir.89.3.1074.
PMID: 8124793
citation: Page RL, Joglar JA, Caldwell MA, Calkins H, Conti JB, Deal BJ, Estes NA III, Field ME, Goldberger ZD, Hammill SC, Indik JH, Lindsay BD, Olshansky B, Russo AM, Shen WK, Tracy CM, Al-Khatib SM. 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm. 2016 Apr;13(4):e136-221. doi: 10.1016/j.hrthm.2015.09.019. Epub 2015 Sep 25. No abstract available.
PMID: 26409100
citation: Shah DC, Takahashi A, Jais P, Hocini M, Clementy J, Haissaguerre M. Local electrogram-based criteria of cavotricuspid isthmus block. J Cardiovasc Electrophysiol. 1999 May;10(5):662-9. doi: 10.1111/j.1540-8167.1999.tb00243.x.
PMID: 10355922
citation: Madaffari A, Krisai P, Spies F, Knecht S, Schaer B, Kojic D, Kuhne M, Sticherling C, Osswald S. Ablation of typical atrial flutter guided by the paced PR interval on the surface electrocardiogram: a proof of concept study. Europace. 2019 Nov 1;21(11):1750-1754. doi: 10.1093/europace/euz208.
PMID: 31384937
citation: Calkins H, Canby R, Weiss R, Taylor G, Wells P, Chinitz L, Milstein S, Compton S, Oleson K, Sherfesee L, Onufer J; 100W Atakr II Investigator Group. Results of catheter ablation of typical atrial flutter. Am J Cardiol. 2004 Aug 15;94(4):437-42. doi: 10.1016/j.amjcard.2004.04.058.
PMID: 15325925
responsible party type: Principal Investigator
investigator affiliation: Centro Medico Teknon
investigator full name: Antonio Berruezo, MD, PhD
investigator title: Research Coordinator of the Heart Institute
mesh term: Atrial Flutter
sharing ipd: No