<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/NCT03003975</url>
  </required_header>
  <id_info>
    <org_study_id>SD-CRYO-AF</org_study_id>
    <nct_id>NCT03003975</nct_id>
  </id_info>
  <brief_title>Single Versus Double Cryoballoon Ablation for Pulmonary Vein Isolation in Patients With Atrial Fibrillation</brief_title>
  <acronym>SD-CRYO-AF</acronym>
  <official_title>Efficacy of Single Versus Double Cryoballoon Ablation for Pulmonary Vein Isolation in Patients With Atrial Fibrillation (SD-Cryo-AF): A Randomized Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Uppsala University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Uppsala University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a clinical study where the investigators will assess the efficacy of a single&#xD;
      cryoballoon application per vein guided by a multipolar recording catheter as compared with a&#xD;
      conventional technique with 2 cryoballoon applications for pulmonary vein isolation (PVI) in&#xD;
      patients with atrial fibrillation (AF).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective, randomized clinical study performed at one centre. The objective is to&#xD;
      assess the efficacy of a single cryoballoon application per vein guided by a multipolar&#xD;
      recording catheter as compared with a conventional technique with 2 cryoballoon applications&#xD;
      for pulmonary vein isolation in patients with atrial fibrillation (AF).&#xD;
&#xD;
      140 subjects with paroxysmal or persistent atrial fibrillation referred for their first AF&#xD;
      ablation procedures will be enrolled.&#xD;
&#xD;
      Recruitment, ablation and follow-up will be performed at Dep of Cardiology in Uppsala&#xD;
      University Hospital, Uppsala, Sweden.&#xD;
&#xD;
      Study duration is 2 years with 12--months enrolment period and 1 year follow-up per subject.&#xD;
&#xD;
      Pulmonary vein isolation (PVI) will be performed using the Arctic Front Advance cryoballoon&#xD;
      ablation catheter. Patients will be randomized to a single cryoballoon application guided by&#xD;
      a multipolar recording catheter or to a conventional technique with 2 cryoballoon&#xD;
      applications. After cryoballoon ablation of all pulmonary veins, PV conduction block will be&#xD;
      assessed by a separate circular mapping catheter. Acute procedural success is defined as&#xD;
      complete electrical isolation of a pulmonary vein assessed by entrance and exit block,&#xD;
      including 20 minutes waiting time. Complications and duration of the procedure will be&#xD;
      assessed.&#xD;
&#xD;
      Patients will be followed at three, six and 12 months after the ablation procedure. A 12 lead&#xD;
      ECG, a 7 day Holter monitoring, quality of life (EQ5D) and EHRA score, will be performed at&#xD;
      baseline, 6 and 12 months. as well as Biomarkers including nTproBNP and troponin I, will be&#xD;
      performed at baseline, and at 6 and 12 months (only nTproBNP). Predictive variables for&#xD;
      successful outcome/AF recurrence will be analysed.&#xD;
&#xD;
      The frequency of symptomatic recurrence of AF and number of reablations will be compared at 6&#xD;
      and 12 months, and in those requiring a redo ablation procedure the status of PV reconduction&#xD;
      will be assessed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2014</start_date>
  <completion_date type="Actual">March 2017</completion_date>
  <primary_completion_date type="Actual">March 2017</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>Frequency of acute pulmonary vein isolation after first ablation.</measure>
    <time_frame>Acute during ablation procedure</time_frame>
    <description>Frequency of complete pulmonary vein isolation after first pass of ablation as per protocol</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Procedure time</measure>
    <time_frame>During ablation procedure</time_frame>
    <description>Procedure time of AF ablation (from initial puncture to removal of sheaths)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fluoroscopy exposure</measure>
    <time_frame>During ablation procedure</time_frame>
    <description>Total time of fluoroscopy for AF ablation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Freedom from atrial fibrillation</measure>
    <time_frame>Evaluated after 12 months</time_frame>
    <description>No atrial fibrillation after first ablation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse/Serious Adverse events</measure>
    <time_frame>Evaluated after 12 months</time_frame>
    <description>Complications during and after ablation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life after ablation</measure>
    <time_frame>Evaluated after 12 months</time_frame>
    <description>Quality of life assessed by EQ5D after ablation compared to baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction of symptom severity score after ablation</measure>
    <time_frame>Evaluated after 12 months</time_frame>
    <description>Symptoms Severity Questionnaire, score reduction after ablation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction of overall symptoms of atrial fibrillation after ablation</measure>
    <time_frame>Evaluated after 12 months</time_frame>
    <description>Symptom assessed by EHRA Symptom Classification score reduction after ablation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cost of ablation procedure</measure>
    <time_frame>Evaluated after initial ablation (within 24 h after ablation)</time_frame>
    <description>Assessed by time for procedure, used resources and equipment during/after ablation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life after ablation (measured as EQ5D score)</measure>
    <time_frame>Evaluated after 12 months</time_frame>
    <description>EQ5D measured before ablation and after 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospitalisation after ablation</measure>
    <time_frame>Evaluated after 12 months</time_frame>
    <description>hospitalisation (no of days)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum troponin I (ng/L) levels after ablation as a predictor of clinical success</measure>
    <time_frame>Evaluated after 12 months</time_frame>
    <description>Maximum troponin I (ng/L) levels as a predictor of freedom from AF after 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nt-proBNP levels before ablation as a predictor of clinical success</measure>
    <time_frame>Evaluated after 12 months</time_frame>
    <description>Nt-proBNP levels as a predictor of freedom from AF after 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Left atrial diameter (mm) before ablation as a predictor of clinical success</measure>
    <time_frame>Evaluated after 12 months</time_frame>
    <description>Left atrial diameter in mm (LAX view) as a predictor of freedom from AF after 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Left atrial volume (ml/m2) before ablation as a predictor of clinical success</measure>
    <time_frame>Evaluated after 12 months</time_frame>
    <description>Left atrial volume (ml/m2) as a predictor of freedom from AF after 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Age (years) as a predictor of clinical success</measure>
    <time_frame>Evaluated after 12 months</time_frame>
    <description>Age at ablation (years) as a predictor of freedom from AF after 12 months; 2 groups; &lt; 70 and &gt;70 years old</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sex as a predictor of clinical success</measure>
    <time_frame>Evaluated after 12 months</time_frame>
    <description>Sex as a predictor of freedom from AF after 12 months. 2 groups; male vs females</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CHADsVASc score as a predictor of clinical success</measure>
    <time_frame>Evaluated after 12 months</time_frame>
    <description>CHADsVASc score as a predictor of freedom from AF after 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BMI (kg/m2) as a predictor of clinical success</measure>
    <time_frame>Evaluated after 12 months</time_frame>
    <description>BMI (kg/m2) as a predictor of freedom from AF after 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Atrial conduction time as a predictor of clinical success</measure>
    <time_frame>Evaluated after 12 months</time_frame>
    <description>Mean conduction time over left atrium as a predictor of freedom from AF after 12 months</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">140</enrollment>
  <condition>Atrial Fibrillation</condition>
  <arm_group>
    <arm_group_label>PVI by single cryoballoon application</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A single cryoballoon application for pulmonary vein isolation will be guided by a Multipolar Recording Catheter (Achieve Mapping Catheter), passed through the inner lumen of the cryoablation catheter. A single application of 4 minutes will be used per vein guided by recording of loss of electrograms and by a defined drop of temperature within 2 minutes application. If a stable position with adequate occlusion of the vein the Achieve catheter should be located proximally for evaluation of entrance block during application, but can be advanced deeper for stability and then retracted to the ostium to evaluate vein isolation (entrance block).&#xD;
If the vein then is isolated after a single application, the operator can move on to the next vein.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PVI by 2 cryo applications</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cryoballoon ablation with a conventional guidewire passed through the inner lumen of the catheter for stability will be used. Ablation will be performed with 2 consecutive applications for 4 minutes each in each vein guided by degree of occlusion and temperature drop at the discretion of the physician.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>PVI by single cryoballoon application guided by Achieve Mapping Catheter</intervention_name>
    <description>Pulmonary vein isolation by single cryoballoon application guided by recorded electrogram signals from an internal Mapping Catheter and by temperature drop if mapping of signals is not possible (temperature cutoff &lt; or = -40 degrees C)</description>
    <arm_group_label>PVI by single cryoballoon application</arm_group_label>
    <other_name>Arctic Front™ Advance Cardiac CryoAblation Catheter</other_name>
    <other_name>Achieve Mapping Catheter</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>PVI by 2 routine cryoballoon applications</intervention_name>
    <description>Pulmonary vein isolation by 2 cryoballoon applications guided by degree of occlusion and by temperature drop according to discretion of physician</description>
    <arm_group_label>PVI by 2 cryo applications</arm_group_label>
    <other_name>Arctic Front™ Advance Cardiac CryoAblation Catheter</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with paroxysmal or persistent AF verified by ECG&#xD;
&#xD;
          -  Patients with symptoms corresponding to at least Europe Heart Rhythm Association&#xD;
             (EHRA) score 2.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Sinus rhythm cannot be maintained for at least one hour after an electrical&#xD;
             cardioversion.&#xD;
&#xD;
          -  Congestive heart failure with New York Heart Association (NYHA) class 3 or more.&#xD;
&#xD;
          -  Left ventricular ejection fraction &lt; 35% not secondary to AF with inadequate rate&#xD;
             control, according to the judgement of the investigator.&#xD;
&#xD;
          -  Left atrial diameter ≥ 55 mm judged by transthoracic echocardiography.&#xD;
&#xD;
          -  Prior AF ablation procedure.&#xD;
&#xD;
          -  Longstanding persistent AF&#xD;
&#xD;
          -  AF secondary to a transient or correctable abnormality including electrolyte&#xD;
             imbalance, trauma, recent surgery, infection, toxic ingestion, and uncontrolled&#xD;
             thyroid disease as well as AF triggered by other uniform supraventricular tachycardia.&#xD;
&#xD;
          -  Contraindication to treatment with anticoagulants.&#xD;
&#xD;
          -  Significant valvular disease or planned cardiac intervention.&#xD;
&#xD;
          -  Hypertrophic cardiomyopathy.&#xD;
&#xD;
          -  Recent cardiac disease states within the last 6 months; unstable angina, acute&#xD;
             myocardial infarction, revascularisation procedures, valve disease&#xD;
&#xD;
          -  Implantable cardioverter-defibrillator (ICD), cardiac resynchronization therapy (CRT)&#xD;
             device.&#xD;
&#xD;
          -  Dual chamber- and single chamber-pacemaker when the patient is pacemaker dependent on&#xD;
             ventricular level&#xD;
&#xD;
          -  Patients with contraindications for transseptal catheterization or appropriate&#xD;
             vascular access is precluded.&#xD;
&#xD;
          -  Renal failure requiring dialysis or abnormalities of liver function tests.&#xD;
&#xD;
          -  Participant in investigational clinical or device trial.&#xD;
&#xD;
          -  Unwilling or unable to give informed consent or inaccessible for follow-up and&#xD;
             psychological problem that might limit compliance.&#xD;
&#xD;
          -  Active abuse of alcohol or other substance which may be causative of AF and/or might&#xD;
             affect compliance.&#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>Carina Blomström Lundqvist, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Uppsala University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Cardiology, University Hospital in Uppsala</name>
      <address>
        <city>Uppsala</city>
        <zip>75185</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>December 9, 2016</study_first_submitted>
  <study_first_submitted_qc>December 21, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 28, 2016</study_first_posted>
  <last_update_submitted>May 7, 2017</last_update_submitted>
  <last_update_submitted_qc>May 7, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 9, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Uppsala University Hospital</investigator_affiliation>
    <investigator_full_name>Carina Blomstrom Lundqvist</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Ablation</keyword>
  <keyword>Cryoballoon</keyword>
  <keyword>Achieve</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</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/NCT03003975
org study id: SD-CRYO-AF
nct id: NCT03003975
lead sponsor: 
has dmc: No
This is a clinical study where the investigators will assess the efficacy of a single
      cryoballoon application per vein guided by a multipolar recording catheter as compared with a
      conventional technique with 2 cryoballoon applications for pulmonary vein isolation (PVI) in
      patients with atrial fibrillation (AF).
This is a prospective, randomized clinical study performed at one centre. The objective is to
      assess the efficacy of a single cryoballoon application per vein guided by a multipolar
      recording catheter as compared with a conventional technique with 2 cryoballoon applications
      for pulmonary vein isolation in patients with atrial fibrillation (AF).

      140 subjects with paroxysmal or persistent atrial fibrillation referred for their first AF
      ablation procedures will be enrolled.

      Recruitment, ablation and follow-up will be performed at Dep of Cardiology in Uppsala
      University Hospital, Uppsala, Sweden.

      Study duration is 2 years with 12--months enrolment period and 1 year follow-up per subject.

      Pulmonary vein isolation (PVI) will be performed using the Arctic Front Advance cryoballoon
      ablation catheter. Patients will be randomized to a single cryoballoon application guided by
      a multipolar recording catheter or to a conventional technique with 2 cryoballoon
      applications. After cryoballoon ablation of all pulmonary veins, PV conduction block will be
      assessed by a separate circular mapping catheter. Acute procedural success is defined as
      complete electrical isolation of a pulmonary vein assessed by entrance and exit block,
      including 20 minutes waiting time. Complications and duration of the procedure will be
      assessed.

      Patients will be followed at three, six and 12 months after the ablation procedure. A 12 lead
      ECG, a 7 day Holter monitoring, quality of life (EQ5D) and EHRA score, will be performed at
      baseline, 6 and 12 months. as well as Biomarkers including nTproBNP and troponin I, will be
      performed at baseline, and at 6 and 12 months (only nTproBNP). Predictive variables for
      successful outcome/AF recurrence will be analysed.

      The frequency of symptomatic recurrence of AF and number of reablations will be compared at 6
      and 12 months, and in those requiring a redo ablation procedure the status of PV reconduction
      will be assessed.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Frequency of acute pulmonary vein isolation after first ablation.
time frame: Acute during ablation procedure
description: Frequency of complete pulmonary vein isolation after first pass of ablation as per protocol
measure: Procedure time
time frame: During ablation procedure
description: Procedure time of AF ablation (from initial puncture to removal of sheaths)
measure: Fluoroscopy exposure
time frame: During ablation procedure
description: Total time of fluoroscopy for AF ablation
measure: Freedom from atrial fibrillation
time frame: Evaluated after 12 months
description: No atrial fibrillation after first ablation
measure: Adverse/Serious Adverse events
time frame: Evaluated after 12 months
description: Complications during and after ablation
measure: Quality of Life after ablation
time frame: Evaluated after 12 months
description: Quality of life assessed by EQ5D after ablation compared to baseline
measure: Reduction of symptom severity score after ablation
time frame: Evaluated after 12 months
description: Symptoms Severity Questionnaire, score reduction after ablation
measure: Reduction of overall symptoms of atrial fibrillation after ablation
time frame: Evaluated after 12 months
description: Symptom assessed by EHRA Symptom Classification score reduction after ablation
measure: Cost of ablation procedure
time frame: Evaluated after initial ablation (within 24 h after ablation)
description: Assessed by time for procedure, used resources and equipment during/after ablation
measure: Quality of life after ablation (measured as EQ5D score)
time frame: Evaluated after 12 months
description: EQ5D measured before ablation and after 12 months
measure: Hospitalisation after ablation
time frame: Evaluated after 12 months
description: hospitalisation (no of days)
measure: Maximum troponin I (ng/L) levels after ablation as a predictor of clinical success
time frame: Evaluated after 12 months
description: Maximum troponin I (ng/L) levels as a predictor of freedom from AF after 12 months
measure: Nt-proBNP levels before ablation as a predictor of clinical success
time frame: Evaluated after 12 months
description: Nt-proBNP levels as a predictor of freedom from AF after 12 months
measure: Left atrial diameter (mm) before ablation as a predictor of clinical success
time frame: Evaluated after 12 months
description: Left atrial diameter in mm (LAX view) as a predictor of freedom from AF after 12 months
measure: Left atrial volume (ml/m2) before ablation as a predictor of clinical success
time frame: Evaluated after 12 months
description: Left atrial volume (ml/m2) as a predictor of freedom from AF after 12 months
measure: Age (years) as a predictor of clinical success
time frame: Evaluated after 12 months
description: Age at ablation (years) as a predictor of freedom from AF after 12 months; 2 groups; < 70 and >70 years old
measure: Sex as a predictor of clinical success
time frame: Evaluated after 12 months
description: Sex as a predictor of freedom from AF after 12 months. 2 groups; male vs females
measure: CHADsVASc score as a predictor of clinical success
time frame: Evaluated after 12 months
description: CHADsVASc score as a predictor of freedom from AF after 12 months
measure: BMI (kg/m2) as a predictor of clinical success
time frame: Evaluated after 12 months
description: BMI (kg/m2) as a predictor of freedom from AF after 12 months
measure: Atrial conduction time as a predictor of clinical success
time frame: Evaluated after 12 months
description: Mean conduction time over left atrium as a predictor of freedom from AF after 12 months
arm group label: PVI by single cryoballoon application
arm group type: Active Comparator
description: A single cryoballoon application for pulmonary vein isolation will be guided by a Multipolar Recording Catheter (Achieve Mapping Catheter), passed through the inner lumen of the cryoablation catheter. A single application of 4 minutes will be used per vein guided by recording of loss of electrograms and by a defined drop of temperature within 2 minutes application. If a stable position with adequate occlusion of the vein the Achieve catheter should be located proximally for evaluation of entrance block during application, but can be advanced deeper for stability and then retracted to the ostium to evaluate vein isolation (entrance block).
If the vein then is isolated after a single application, the operator can move on to the next vein.
arm group label: PVI by 2 cryo applications
arm group type: Active Comparator
description: Cryoballoon ablation with a conventional guidewire passed through the inner lumen of the catheter for stability will be used. Ablation will be performed with 2 consecutive applications for 4 minutes each in each vein guided by degree of occlusion and temperature drop at the discretion of the physician.
intervention type: Device
intervention name: PVI by single cryoballoon application guided by Achieve Mapping Catheter
description: Pulmonary vein isolation by single cryoballoon application guided by recorded electrogram signals from an internal Mapping Catheter and by temperature drop if mapping of signals is not possible (temperature cutoff < or = -40 degrees C)
arm group label: PVI by single cryoballoon application
other name: Arctic Front™ Advance Cardiac CryoAblation Catheter
other name: Achieve Mapping Catheter
intervention type: Device
intervention name: PVI by 2 routine cryoballoon applications
description: Pulmonary vein isolation by 2 cryoballoon applications guided by degree of occlusion and by temperature drop according to discretion of physician
arm group label: PVI by 2 cryo applications
other name: Arctic Front™ Advance Cardiac CryoAblation Catheter
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Carina Blomström Lundqvist, Professor
role: Principal Investigator
affiliation: Uppsala University
facility: 
country: Sweden
responsible party type: Principal Investigator
investigator affiliation: Uppsala University Hospital
investigator full name: Carina Blomstrom Lundqvist
investigator title: Professor
mesh term: Atrial Fibrillation
sharing ipd: No