<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/NCT02208102</url>
  </required_header>
  <id_info>
    <org_study_id>TCAI_IMPACT II</org_study_id>
    <nct_id>NCT02208102</nct_id>
  </id_info>
  <brief_title>Role of Cardiac Biomarkers in Prediction of Outcome in Atrial Fibrillation Patients Undergoing Catheter Ablation</brief_title>
  <acronym>IMPACTII</acronym>
  <official_title>Association of Cardiac Biomarkers With AF Ablation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Texas Cardiac Arrhythmia Research Foundation</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Texas Cardiac Arrhythmia Research Foundation</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess if pre-ablation levels of inflammatory biomarkers&#xD;
      serve as independent predictors of procedure outcome To evaluate the inflammatory activation&#xD;
      following catheter ablation by measuring serum-biomarker levels 24-hours after the procedure&#xD;
      and examine the predictive role in procedure success To study the association of certain&#xD;
      biomarkers with specific types of AF (paroxysmal or persistent or long standing persistent)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Specific Aim: The purpose of this prospective study is to evaluate the role of inflammatory&#xD;
      biomarkers in predicting procedure-outcome in AF patients undergoing catheter ablation.&#xD;
&#xD;
      Background: AF is the most common arrhythmia in clinical practice, affecting &gt; 2.3 million&#xD;
      people in US. It increases dramatically with age and is seen in as many as 9% of individuals&#xD;
      by the age of 80 (1). A major cause of stroke, AF is also associated with a 2-fold increase&#xD;
      in mortality (1).&#xD;
&#xD;
      Symptomatic AF has been demonstrated to be consistently associated with elevated inflammatory&#xD;
      activity in the atrial tissue as evidenced by the facts that AF occurs in 40% of patients&#xD;
      following cardiac bypass surgery and 50% of patients undergoing valvular surgery (2). Recent&#xD;
      studies have also demonstrated that elevated CRP level can increase the risk of AF up to 31%&#xD;
      (2). Oxidative damage experienced during AF leads to myocardial necrosis which in turn&#xD;
      induces low-grade inflammation resulting in eventual fibrosis of the atrial myocardium. Thus,&#xD;
      inflammation can be responsible for adverse structural and electrical remodeling of the&#xD;
      cardiac tissue which can further perpetuate the existence, maintenance, and recurrence of&#xD;
      this arrhythmia.&#xD;
&#xD;
      Radiofrequency catheter ablation (RFCA) has evolved as a promising curative therapy for&#xD;
      drug-refractory AF. However, the recurrence of AF after RFCA is a common clinical problem,&#xD;
      occurring in 25-50% of patients in the follow-up period (3) and some patients undergo&#xD;
      multiple ablation procedures before being cured of the arrhythmia. Published retrospective&#xD;
      studies have demonstrated that systemic inflammation generated during AF ablation is&#xD;
      associated with fewer early arrhythmia recurrences (4). Therefore, measurement of&#xD;
      inflammatory markers within 24 hours of RFCA could be helpful in further exploration of any&#xD;
      association between the degree of inflammatory activation and procedure outcome.&#xD;
&#xD;
      Myriad Rules-Based Medicine, Inc (Myriad RBM) in Austin, TX 78759 has developed biomarker&#xD;
      panels that have been validated to detect early signs of inflammation. Myriad RBM will&#xD;
      process the blood samples on a preliminary panel of 77 biomarkers, identified to be possible&#xD;
      predictors of procedural outcome in RFCA in AF patients.&#xD;
&#xD;
      Study design:&#xD;
&#xD;
      This study will assess a panel of 77 biomarkers in human serum samples that have been&#xD;
      identified by the pilot study results as the potential predictors of procedural outcome in&#xD;
      catheter ablation for AF. The study population will consist of 150 volunteering patients with&#xD;
      AF undergoing RFCA. Blood samples will be collected at two time points from each patient; one&#xD;
      at baseline and the other in the morning after the procedure.&#xD;
&#xD;
      Study Procedure:&#xD;
&#xD;
      For each patient, one 8.5 ml tube of whole blood will be collected via venipuncture before&#xD;
      and the morning after the ablation procedure.&#xD;
&#xD;
      Ablation Procedure:&#xD;
&#xD;
      Standard radiofrequency catheter ablation procedure will occur in accordance with the&#xD;
      physician's discretion.&#xD;
&#xD;
      Blood sample collection:&#xD;
&#xD;
      The whole blood sample will be collected in a Serum Separator Tube (SST) using BD&#xD;
      venipuncture procedure, and labeled with an anonymous patient identifier. Only clinical&#xD;
      research staff will be able to identify study participants.&#xD;
&#xD;
      Following collection, the samples will be centrifuged for 15 minutes at 900Xg at room&#xD;
      temperature, within two hours of collection. Plasma, located as a clear straw-color fluid at&#xD;
      the top of the specimen, would be transferred to another sterile tube and stored at -200 C.&#xD;
      Samples will be picked up weekly by the RBM team to be stored at -800 C until the end of the&#xD;
      study, when all samples will be simultaneously analyzed.&#xD;
&#xD;
      Limited information will also be recorded such as age, gender, height, weight, caffeine&#xD;
      intake and information about medications, smoking history, family history of atrial&#xD;
      fibrillation (if known), and information about the outcome of the procedure. Researchers at&#xD;
      RBM will be blinded to the patient history and demographic data.&#xD;
&#xD;
      After this study is complete the researchers at RBM will store any leftover blood. The&#xD;
      researchers may use the leftover samples in future unspecified research studies, which may or&#xD;
      may not be related to the AF procedure. Even if the blood sample is used for other studies,&#xD;
      the researchers will not have a way to identify the patient.&#xD;
&#xD;
      Follow-Up:&#xD;
&#xD;
      At the 6 and 12 month time points, information will be collected from the medical record&#xD;
      regarding recurrence of AF.&#xD;
&#xD;
      Risk Analysis:&#xD;
&#xD;
      Minor risks associated with a venous blood draw may include fainting or bruising, pain or&#xD;
      discomfort and a 1/1000 risk of infection at the site where blood is drawn.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">May 2016</completion_date>
  <primary_completion_date type="Actual">April 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Arrhythmia recurrence</measure>
    <time_frame>1 year</time_frame>
    <description>Patients will be monitored for arrhythmia recurrence for 1 year after the ablation procedure. At the end of the study, biomarker data will be analyzed to see any predictive association with AFib recurrence</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Left atrial scar</measure>
    <time_frame>During ablation procedure</time_frame>
    <description>if atrial scar is detected during the first ablation procedure, we will assess the association of scar with any of the 77 biomarkers, specifically those indicating fibrosis</description>
  </secondary_outcome>
  <enrollment type="Actual">155</enrollment>
  <condition>Atrial Fibrillation</condition>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Radio-frequency catheter ablation</intervention_name>
    <other_name>RFCA</other_name>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Plasma from whole blood&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients undergoing catheter ablation for atrial fibrillation&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Age: 50-70 years&#xD;
&#xD;
          -  Patients undergoing catheter ablation of atrial fibrillation&#xD;
&#xD;
          -  Able and willing to give written consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Reversible causes of AF such as pericarditis and hyperthyroidism&#xD;
&#xD;
               -  Associated chronic inflammatory diseases such as chronic gingivitis or&#xD;
                  peri-odontitis, rheumatoid Arthritis, IBD including Ulcerative Colitis and&#xD;
                  Crohn's disease, Lupus, Ankylosing Spondylitis, COPD, psoriasis, vasculitis&#xD;
&#xD;
               -  Any other co-morbid conditions except Diabetes and hypertension&#xD;
&#xD;
               -  Patients taking long-term anti-inflammatory, steroid medication, or immune&#xD;
                  suppression medication.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Texas Cardiac Arrhythmia Institute, St. david's Medical Center</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78727</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>July 31, 2014</study_first_submitted>
  <study_first_submitted_qc>August 1, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 4, 2014</study_first_posted>
  <last_update_submitted>October 17, 2017</last_update_submitted>
  <last_update_submitted_qc>October 17, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 19, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>atrial fibrillation, catheter ablation, blood-biomarkers</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</mesh_term>
  </condition_browse>
  <!-- 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/NCT02208102
org study id: TCAI_IMPACT II
nct id: NCT02208102
lead sponsor: 
has dmc: No
The purpose of this study is to assess if pre-ablation levels of inflammatory biomarkers
      serve as independent predictors of procedure outcome To evaluate the inflammatory activation
      following catheter ablation by measuring serum-biomarker levels 24-hours after the procedure
      and examine the predictive role in procedure success To study the association of certain
      biomarkers with specific types of AF (paroxysmal or persistent or long standing persistent)
Specific Aim: The purpose of this prospective study is to evaluate the role of inflammatory
      biomarkers in predicting procedure-outcome in AF patients undergoing catheter ablation.

      Background: AF is the most common arrhythmia in clinical practice, affecting > 2.3 million
      people in US. It increases dramatically with age and is seen in as many as 9% of individuals
      by the age of 80 (1). A major cause of stroke, AF is also associated with a 2-fold increase
      in mortality (1).

      Symptomatic AF has been demonstrated to be consistently associated with elevated inflammatory
      activity in the atrial tissue as evidenced by the facts that AF occurs in 40% of patients
      following cardiac bypass surgery and 50% of patients undergoing valvular surgery (2). Recent
      studies have also demonstrated that elevated CRP level can increase the risk of AF up to 31%
      (2). Oxidative damage experienced during AF leads to myocardial necrosis which in turn
      induces low-grade inflammation resulting in eventual fibrosis of the atrial myocardium. Thus,
      inflammation can be responsible for adverse structural and electrical remodeling of the
      cardiac tissue which can further perpetuate the existence, maintenance, and recurrence of
      this arrhythmia.

      Radiofrequency catheter ablation (RFCA) has evolved as a promising curative therapy for
      drug-refractory AF. However, the recurrence of AF after RFCA is a common clinical problem,
      occurring in 25-50% of patients in the follow-up period (3) and some patients undergo
      multiple ablation procedures before being cured of the arrhythmia. Published retrospective
      studies have demonstrated that systemic inflammation generated during AF ablation is
      associated with fewer early arrhythmia recurrences (4). Therefore, measurement of
      inflammatory markers within 24 hours of RFCA could be helpful in further exploration of any
      association between the degree of inflammatory activation and procedure outcome.

      Myriad Rules-Based Medicine, Inc (Myriad RBM) in Austin, TX 78759 has developed biomarker
      panels that have been validated to detect early signs of inflammation. Myriad RBM will
      process the blood samples on a preliminary panel of 77 biomarkers, identified to be possible
      predictors of procedural outcome in RFCA in AF patients.

      Study design:

      This study will assess a panel of 77 biomarkers in human serum samples that have been
      identified by the pilot study results as the potential predictors of procedural outcome in
      catheter ablation for AF. The study population will consist of 150 volunteering patients with
      AF undergoing RFCA. Blood samples will be collected at two time points from each patient; one
      at baseline and the other in the morning after the procedure.

      Study Procedure:

      For each patient, one 8.5 ml tube of whole blood will be collected via venipuncture before
      and the morning after the ablation procedure.

      Ablation Procedure:

      Standard radiofrequency catheter ablation procedure will occur in accordance with the
      physician's discretion.

      Blood sample collection:

      The whole blood sample will be collected in a Serum Separator Tube (SST) using BD
      venipuncture procedure, and labeled with an anonymous patient identifier. Only clinical
      research staff will be able to identify study participants.

      Following collection, the samples will be centrifuged for 15 minutes at 900Xg at room
      temperature, within two hours of collection. Plasma, located as a clear straw-color fluid at
      the top of the specimen, would be transferred to another sterile tube and stored at -200 C.
      Samples will be picked up weekly by the RBM team to be stored at -800 C until the end of the
      study, when all samples will be simultaneously analyzed.

      Limited information will also be recorded such as age, gender, height, weight, caffeine
      intake and information about medications, smoking history, family history of atrial
      fibrillation (if known), and information about the outcome of the procedure. Researchers at
      RBM will be blinded to the patient history and demographic data.

      After this study is complete the researchers at RBM will store any leftover blood. The
      researchers may use the leftover samples in future unspecified research studies, which may or
      may not be related to the AF procedure. Even if the blood sample is used for other studies,
      the researchers will not have a way to identify the patient.

      Follow-Up:

      At the 6 and 12 month time points, information will be collected from the medical record
      regarding recurrence of AF.

      Risk Analysis:

      Minor risks associated with a venous blood draw may include fainting or bruising, pain or
      discomfort and a 1/1000 risk of infection at the site where blood is drawn.
observational model: Cohort
time perspective: Prospective
measure: Arrhythmia recurrence
time frame: 1 year
description: Patients will be monitored for arrhythmia recurrence for 1 year after the ablation procedure. At the end of the study, biomarker data will be analyzed to see any predictive association with AFib recurrence
measure: Left atrial scar
time frame: During ablation procedure
description: if atrial scar is detected during the first ablation procedure, we will assess the association of scar with any of the 77 biomarkers, specifically those indicating fibrosis
intervention type: Procedure
intervention name: Radio-frequency catheter ablation
other name: RFCA
Plasma from whole blood
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 50 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Atrial Fibrillation