<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/NCT04463641</url>
  </required_header>
  <id_info>
    <org_study_id>LAXI01</org_study_id>
    <nct_id>NCT04463641</nct_id>
  </id_info>
  <brief_title>Assessment of the Axone Micro Quadripolar Lead for Enhanced Cardiac Resynchronization Therapy</brief_title>
  <acronym>ASTRAL-4LV</acronym>
  <official_title>Assessment of the Axone Micro Quadripolar Lead for Enhanced Cardiac Resynchronization Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>MicroPort CRM</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>MicroPort CRM</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The primary objective of this study is to assess the chronic safety and performance of the&#xD;
      Axone left ventricular (LV) micro-lead.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a interventional, pivotal, prospective, single arm, open label, multicenter,&#xD;
      international trial.&#xD;
&#xD;
      The device under investigation is the Axone system, consisting of:&#xD;
&#xD;
        -  Axone 4LV: an ultrathin, lumenless, quadripolar, IS4-compatible lead designed for left&#xD;
           ventricular pacing for cardiac resynchronization therapy (CRT).&#xD;
&#xD;
        -  Axone µGuide: a dedicated, permanently implantable micro catheter designed for&#xD;
           implantation of the Axone 4LV lead.&#xD;
&#xD;
      The primary endpoint data will be used to support CE marking of the Axone system.&#xD;
&#xD;
      The primary endpoints will be evaluated at 6 months post-implantation. Subjects will be&#xD;
      followed-up at 6 weeks, 3 months, 6 months, 12 months post-implantation, then yearly until 4&#xD;
      years post-implantation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 3, 2020</start_date>
  <completion_date type="Anticipated">December 2027</completion_date>
  <primary_completion_date type="Anticipated">June 2024</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety co-primary endpoint, defined as Axone system related complication free rate at 6 months post implant</measure>
    <time_frame>6 months</time_frame>
    <description>A complication is defined as any Serious Adverse Device Effect (SADE) resulting in death or requiring invasive intervention. Safety co-primary endpoint assessment will be based on independent event adjudication by a Clinical Event Committee (CEC).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Performance co-primary endpoint, defined as LV pacing success rate at 6 months post implant</measure>
    <time_frame>6 months</time_frame>
    <description>LV pacing success is defined as at least one LV pacing vector with:&#xD;
Pacing Threshold (PT) ≤ 3.5V at 1ms pulse width, and&#xD;
No phrenic nerve stimulation at PT+2V / 1ms pulse width.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Bizone LV pacing success rate at 6 months post implant</measure>
    <time_frame>6 months</time_frame>
    <description>Bizone LV pacing success is defined as two distant pacing vectors with:&#xD;
A Pacing Threshold (PT) ≤ 3.5V at 1ms pulse width, and&#xD;
No phrenic nerve stimulation at PT +2V / 1ms pulse width. Two pacing vectors are considered distant when cathode electrodes are separated by at least 30 mm.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Axone 4LV implantation success rate</measure>
    <time_frame>At implant, preferably within 15 days of enrollment</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Implantation duration</measure>
    <time_frame>At implant, preferably within 15 days of enrollment</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Fluoroscopy time</measure>
    <time_frame>At implant, preferably within 15 days of enrollment</time_frame>
    <description>Fluoroscopy time is measured in minutes</description>
  </other_outcome>
  <other_outcome>
    <measure>Fluoroscopy dose</measure>
    <time_frame>At implant, preferably within 15 days of enrollment</time_frame>
    <description>Fluoroscopy dose is measured using dose area product (Gray.cm^2)</description>
  </other_outcome>
  <other_outcome>
    <measure>Axone system handling assessment</measure>
    <time_frame>At implant, preferably within 15 days of enrollment</time_frame>
    <description>Implanters will be asked to fill in a handling questionnaire and record observations related to the use of the Axone system.</description>
  </other_outcome>
  <other_outcome>
    <measure>Axone implanters' learning curve</measure>
    <time_frame>At implant, preferably within 15 days of enrollment</time_frame>
    <description>This endpoint will be based on fluoroscopy time for implantation. The effect of removing the 1st, 2nd, 3rd, etc implanted subjects on mean fluoroscopy time (per implanter and per site) will be calculated.</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of excitable myocardium areas at implant</measure>
    <time_frame>At implant, preferably within 15 days of enrollment</time_frame>
    <description>&quot;Excitable myocardium areas&quot; are areas that can be paced by the implanted Axone 4LV lead.</description>
  </other_outcome>
  <other_outcome>
    <measure>Effect of CRT therapy, in particular bizone pacing, on QRS parameters, at discharge and 6 months post implant</measure>
    <time_frame>At discharge, within 7 days of implant, and at 6 months</time_frame>
    <description>The effect of monozone and bizone CRT pacing on duration of QRS is measured in milliseconds.</description>
  </other_outcome>
  <other_outcome>
    <measure>Effect of CRT therapy, in particular bizone pacing, on Left Pre-Ejection Interval (LPEI), at discharge</measure>
    <time_frame>At discharge, within 7 days of implant</time_frame>
    <description>LPEI (in milliseconds) is an electromechanical parameter that can be assessed using echocardiography.</description>
  </other_outcome>
  <other_outcome>
    <measure>Axone 4LV lead pacing threshold</measure>
    <time_frame>Discharge (within 7 days of implant), 6 weeks, 3 months, 6 months, 12 months, 24 months 36 months, 48 months</time_frame>
    <description>Pacing threshold is measured in Volts.</description>
  </other_outcome>
  <other_outcome>
    <measure>Axone 4LV lead pacing impedance</measure>
    <time_frame>Discharge (within 7 days of implant), 6 weeks, 3 months, 6 months, 12 months, 24 months 36 months, 48 months</time_frame>
    <description>Pacing impedance is measured in Ohms.</description>
  </other_outcome>
  <other_outcome>
    <measure>Presence of phrenic nerve stimulation (PNS) with the Axone 4LV lead</measure>
    <time_frame>Implant (preferably within 15 days of enrollment), discharge (within 7 days of implant), 6 weeks, 3 months, 6 months</time_frame>
    <description>The presence of PNS will be assessed at 10V using an external pacing system analyzer at implant, or at pacing threshold +2V at other visits.</description>
  </other_outcome>
  <other_outcome>
    <measure>Axone 4LV lead programming</measure>
    <time_frame>Discharge (within 7 days of implant), 6 weeks, 3 months, 6 months, 12 months, 24 months 36 months, 48 months</time_frame>
    <description>Lead programming will be reported using: (i) pacing amplitude (Volts), pulse width (milliseconds) and pacing vector(s) selected.</description>
  </other_outcome>
  <other_outcome>
    <measure>Energy consumption associated with Axone 4LV lead</measure>
    <time_frame>6 months</time_frame>
    <description>Energy will be calculated using the formula: E=(pacing amplitude^2 x pulse width)/impedance. Energy, pacing amplitude, pulse width and impedance are measured in Joules, Volts, milliseconds, and Ohms, respectively.</description>
  </other_outcome>
  <other_outcome>
    <measure>Axone system-related annual complication-free rate</measure>
    <time_frame>12 months, 24 months 36 months, 48 months</time_frame>
    <description>Definition of Axone system related complication is the same as for primary safety endpoint.</description>
  </other_outcome>
  <other_outcome>
    <measure>Clinical response to CRT at 12 months post implant</measure>
    <time_frame>12 months</time_frame>
    <description>Clinical response will be determined by looking at functional improvement, reverse remodelling, freedom from heart failure events, and rate of non-responders:&#xD;
(i) functional improvement is defined as improvement in ≥1 NYHA (New York Heart Association) class from baseline to 12 months.&#xD;
(ii) reverse remodelling is a ≥12% increase in left ventricular end systolic volume index (LVESVi: LVESV [mL] and body surface area [m^2] will be combined to report LVESVi).&#xD;
(iii) freedom from heart failure events is defined as an absence of death or HF hospitalization.&#xD;
(iv) non-responders are all those who are not responders. A responder is defined as a subject that is not dead and who did not experience any HF hospitalization and that has a stable or improved NYHA class versus baseline.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">152</enrollment>
  <condition>Heart Failure</condition>
  <condition>Cardiac Resynchronization Therapy</condition>
  <arm_group>
    <arm_group_label>Axone 4LV Lead</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects implanted with the Axone 4LV Lead</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Implantation of the Axone 4LV Lead</intervention_name>
    <description>Implantation of the Axone 4LV Lead</description>
    <arm_group_label>Axone 4LV Lead</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Indication for cardiac resynchronization therapy-defibrillator (CRT-D) device implant&#xD;
             according to the latest ESC (European Society of Cardiology) guidelines&#xD;
&#xD;
          -  De-novo implant of a Platinium 4LV CRT-D device (or any newer 4LV CRT-D model&#xD;
             manufactured by MicroPort CRM)&#xD;
&#xD;
          -  Reviewed, signed and dated informed consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  LV lead previous implant attempt&#xD;
&#xD;
          -  Upgrade to CRT from a previously implanted pacemaker or implantable&#xD;
             cardioverter-defibrillator (ICD), or CRT device replacement&#xD;
&#xD;
          -  Known allergy to contrast media used for imaging during cardiac catheterization&#xD;
&#xD;
          -  Tricuspid valvular disease or any type of tricuspid replacement heart valve&#xD;
             (mechanical or tissue)&#xD;
&#xD;
          -  Severe renal failure (creatinine clearance according to the Modification of Diet in&#xD;
             Renal Disease (MDRD) formula &lt; 30ml/min/m²)&#xD;
&#xD;
          -  Active myocarditis&#xD;
&#xD;
          -  Stroke, myocardial infarction or cardiac revascularization within 40 days prior to&#xD;
             implant&#xD;
&#xD;
          -  Previous heart transplant or currently on heart transplant list&#xD;
&#xD;
          -  Life expectancy less than 1 year&#xD;
&#xD;
          -  Already included in another clinical study that could confound the results of this&#xD;
             study&#xD;
&#xD;
          -  Pre-menopausal women / women in childbearing age, including pregnant and breastfeeding&#xD;
             women&#xD;
&#xD;
          -  Less than 18 years old or under guardianship&#xD;
&#xD;
          -  Incapacitated subject, inability to understand the purpose of the study, or to meet&#xD;
             follow-up visits at the implanting site as defined in the protocol&#xD;
&#xD;
          -  Diagnosis of drug addiction (substance use disorder)&#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>Frédéric Anselme, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU de Rouen, France</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Anaïs Balland, MSc</last_name>
    <phone>+33602000014</phone>
    <email>anais.balland@crm.microport.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Kepler Universitätsklinikum</name>
      <address>
        <city>Linz</city>
        <country>Austria</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Clemens Steinwender, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CH Annecy Genevois</name>
      <address>
        <city>Annecy</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Antoine Dompnier, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHRU Hopital Trousseau</name>
      <address>
        <city>Chambray-lès-Tours</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Bertrand Pierre, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Clermont-Ferrand</name>
      <address>
        <city>Clermont-Ferrand</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Frédéric Jean, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Grenoble</name>
      <address>
        <city>Grenoble</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Pascal Defaye, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHRU de Lille - Hôpital Cardiologique</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Christelle Marquié, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Pontchaillou</name>
      <address>
        <city>Rennes</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Christophe Leclercq, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Rouen</name>
      <address>
        <city>Rouen</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Frédéric Anselme, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Toulouse</name>
      <address>
        <city>Toulouse</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Pierre Mondoly, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Hamburg Eppendorf</name>
      <address>
        <city>Hamburg</city>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Tobias Toennis, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Heidelberg</name>
      <address>
        <city>Heidelberg</city>
        <country>Germany</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Panagiotis Xynogalos, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Schleswig-Holstein Campus Kiel</name>
      <address>
        <city>Kiel</city>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Evgeny Lyan, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>ASST Spedali Civili di Brescia</name>
      <address>
        <city>Brescia</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Antonio Curnis, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ospedale Pellegrini</name>
      <address>
        <city>Naples</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Valentino Ducceschi, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ospedale Policlinico Federico II</name>
      <address>
        <city>Naples</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Antonio Rapacciuolo, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Isala Klinieken</name>
      <address>
        <city>Zwolle</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Peter Paul Delnoy, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centro Hospitalar Universitário Lisboa Norte - Hospital de Santa Maria</name>
      <address>
        <city>Lisbon</city>
        <country>Portugal</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Pedro Marques, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centro Hospitalar Universitário do Porto</name>
      <address>
        <city>Porto</city>
        <country>Portugal</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Hipolito Reis, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario General de Alicante</name>
      <address>
        <city>Alicante</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Juan Gabriel Martinez, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Fe</name>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Joaquin Osca, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Álvaro Cunqueiro</name>
      <address>
        <city>Vigo</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Elvis Teijeira, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Portugal</country>
    <country>Spain</country>
  </location_countries>
  <reference>
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    <citation>Zeitler EP, Friedman DJ, Daubert JP, Al-Khatib SM, Solomon SD, Biton Y, McNitt S, Zareba W, Moss AJ, Kutyifa V. Multiple Comorbidities and Response to Cardiac Resynchronization Therapy: MADIT-CRT Long-Term Follow-Up. J Am Coll Cardiol. 2017 May 16;69(19):2369-2379. doi: 10.1016/j.jacc.2017.03.531.</citation>
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    <citation>Daubert C, Behar N, Martins RP, Mabo P, Leclercq C. Avoiding non-responders to cardiac resynchronization therapy: a practical guide. Eur Heart J. 2017 May 14;38(19):1463-1472. doi: 10.1093/eurheartj/ehw270.</citation>
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    <citation>Okamura H. Up-to-date cardiac resynchronization therapy. J Gen Fam Med. 2017 May 17;18(5):195-199. doi: 10.1002/jgf2.24. eCollection 2017 Oct.</citation>
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  </reference>
  <reference>
    <citation>Macias A, Gavira JJ, Alegria E, Azcarate PM, Barba J, Garcia-Bolao I. [Effect of the left ventricular pacing site on echocardiographic parameters of ventricular dyssynchrony in patients receiving cardiac resynchronization therapy]. Rev Esp Cardiol. 2004 Feb;57(2):138-45. Spanish.</citation>
    <PMID>14967109</PMID>
  </reference>
  <reference>
    <citation>Butter C, Auricchio A, Stellbrink C, Fleck E, Ding J, Yu Y, Huvelle E, Spinelli J; Pacing Therapy for Chronic Heart Failure II Study Group. Effect of resynchronization therapy stimulation site on the systolic function of heart failure patients. Circulation. 2001 Dec 18;104(25):3026-9. doi: 10.1161/hc5001.102229.</citation>
    <PMID>11748094</PMID>
  </reference>
  <reference>
    <citation>Umar F, Taylor RJ, Stegemann B, Marshall H, Flannigan S, Lencioni M, De Bono J, Griffith M, Leyva F. Haemodynamic effects of cardiac resynchronization therapy using single-vein, three-pole, multipoint left ventricular pacing in patients with ischaemic cardiomyopathy and a left ventricular free wall scar: the MAESTRO study. Europace. 2016 Aug;18(8):1227-34. doi: 10.1093/europace/euv396. Epub 2015 Dec 30.</citation>
    <PMID>26718535</PMID>
  </reference>
  <reference>
    <citation>Bonadei I, Vizzardi E, Gorga E, Carubelli V, Pagnoni M, Sciatti E, Raweh A, Cerini M, Bontempi L, Curnis A, Metra M. Role of the old and new echocardiographic technologies in cardiac resynchronization therapy. Minerva Cardioangiol. 2016 Oct;64(5):572-80. Epub 2015 Jun 23.</citation>
    <PMID>26099222</PMID>
  </reference>
  <reference>
    <citation>O'Brien T, Park MS, Youn JC, Chung ES. The Past, Present and Future of Cardiac Resynchronization Therapy. Korean Circ J. 2019 May;49(5):384-399. doi: 10.4070/kcj.2019.0114.</citation>
    <PMID>31074211</PMID>
  </reference>
  <reference>
    <citation>Leclercq C, Burri H, Curnis A, Delnoy PP, Rinaldi CA, Sperzel J, Lee K, Calo L, Vicentini A, Concha JF, Thibault B. Cardiac resynchronization therapy non-responder to responder conversion rate in the more response to cardiac resynchronization therapy with MultiPoint Pacing (MORE-CRT MPP) study: results from Phase I. Eur Heart J. 2019 Sep 14;40(35):2979-2987. doi: 10.1093/eurheartj/ehz109.</citation>
    <PMID>30859220</PMID>
  </reference>
  <reference>
    <citation>Auricchio A, Heggermont WA. Technology Advances to Improve Response to Cardiac Resynchronization Therapy: What Clinicians Should Know. Rev Esp Cardiol (Engl Ed). 2018 Jun;71(6):477-484. doi: 10.1016/j.rec.2018.01.006. Epub 2018 Feb 14. English, Spanish.</citation>
    <PMID>29454549</PMID>
  </reference>
  <reference>
    <citation>Antoniadis AP, Behar JM, Sieniewicz B, Gould J, Niederer S, Rinaldi CA. A comparison of the different features of quadripolar left ventricular pacing leads to deliver cardiac resynchronization therapy. Expert Rev Med Devices. 2017 Sep;14(9):697-706. doi: 10.1080/17434440.2017.1369404. Epub 2017 Aug 23.</citation>
    <PMID>28835138</PMID>
  </reference>
  <reference>
    <citation>Tomassoni G, Baker J, Corbisiero R, Love C, Martin D, Niazi I, Sheppard R, Worley S, Beau S, Greer GS, Aryana A, Cao M, Harbert N, Zhang S; Promote(R) Q CRT-D and Quartet(R) Left Ventricular Heart Lead Study Group. Postoperative performance of the Quartet(R) left ventricular heart lead. J Cardiovasc Electrophysiol. 2013 Apr;24(4):449-56. doi: 10.1111/jce.12065. Epub 2013 Jan 22.</citation>
    <PMID>23339555</PMID>
  </reference>
  <reference>
    <citation>Crossley GH, Biffi M, Johnson B, Lin A, Gras D, Hussin A, Cuffio A, Collier JL, El-Chami M, Li S, Holloman K, Exner DV. Performance of a novel left ventricular lead with short bipolar spacing for cardiac resynchronization therapy: primary results of the Attain Performa quadripolar left ventricular lead study. Heart Rhythm. 2015 Apr;12(4):751-8. doi: 10.1016/j.hrthm.2014.12.019. Epub 2014 Dec 19.</citation>
    <PMID>25533587</PMID>
  </reference>
  <reference>
    <citation>Mittal S, Nair D, Padanilam BJ, Ciuffo A, Gupta N, Gallagher P, Goldner B, Hammill EF, Wold N, Stein K, Burke M. Performance of Anatomically Designed Quadripolar Left Ventricular Leads: Results from the NAVIGATE X4 Clinical Trial. J Cardiovasc Electrophysiol. 2016 Oct;27(10):1199-1205. doi: 10.1111/jce.13044. Epub 2016 Aug 19.</citation>
    <PMID>27434039</PMID>
  </reference>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>June 23, 2020</study_first_submitted>
  <study_first_submitted_qc>July 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 9, 2020</study_first_posted>
  <last_update_submitted>October 11, 2022</last_update_submitted>
  <last_update_submitted_qc>October 11, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Left Ventricular Lead</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</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/NCT04463641
org study id: LAXI01
nct id: NCT04463641
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The primary objective of this study is to assess the chronic safety and performance of the
      Axone left ventricular (LV) micro-lead.
This is a interventional, pivotal, prospective, single arm, open label, multicenter,
      international trial.

      The device under investigation is the Axone system, consisting of:

        -  Axone 4LV: an ultrathin, lumenless, quadripolar, IS4-compatible lead designed for left
           ventricular pacing for cardiac resynchronization therapy (CRT).

        -  Axone µGuide: a dedicated, permanently implantable micro catheter designed for
           implantation of the Axone 4LV lead.

      The primary endpoint data will be used to support CE marking of the Axone system.

      The primary endpoints will be evaluated at 6 months post-implantation. Subjects will be
      followed-up at 6 weeks, 3 months, 6 months, 12 months post-implantation, then yearly until 4
      years post-implantation.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety co-primary endpoint, defined as Axone system related complication free rate at 6 months post implant
time frame: 6 months
description: A complication is defined as any Serious Adverse Device Effect (SADE) resulting in death or requiring invasive intervention. Safety co-primary endpoint assessment will be based on independent event adjudication by a Clinical Event Committee (CEC).
measure: Performance co-primary endpoint, defined as LV pacing success rate at 6 months post implant
time frame: 6 months
description: LV pacing success is defined as at least one LV pacing vector with:
Pacing Threshold (PT) ≤ 3.5V at 1ms pulse width, and
No phrenic nerve stimulation at PT+2V / 1ms pulse width.
measure: Bizone LV pacing success rate at 6 months post implant
time frame: 6 months
description: Bizone LV pacing success is defined as two distant pacing vectors with:
A Pacing Threshold (PT) ≤ 3.5V at 1ms pulse width, and
No phrenic nerve stimulation at PT +2V / 1ms pulse width. Two pacing vectors are considered distant when cathode electrodes are separated by at least 30 mm.
measure: Axone 4LV implantation success rate
time frame: At implant, preferably within 15 days of enrollment
measure: Implantation duration
time frame: At implant, preferably within 15 days of enrollment
measure: Fluoroscopy time
time frame: At implant, preferably within 15 days of enrollment
description: Fluoroscopy time is measured in minutes
measure: Fluoroscopy dose
time frame: At implant, preferably within 15 days of enrollment
description: Fluoroscopy dose is measured using dose area product (Gray.cm^2)
measure: Axone system handling assessment
time frame: At implant, preferably within 15 days of enrollment
description: Implanters will be asked to fill in a handling questionnaire and record observations related to the use of the Axone system.
measure: Axone implanters' learning curve
time frame: At implant, preferably within 15 days of enrollment
description: This endpoint will be based on fluoroscopy time for implantation. The effect of removing the 1st, 2nd, 3rd, etc implanted subjects on mean fluoroscopy time (per implanter and per site) will be calculated.
measure: Number of excitable myocardium areas at implant
time frame: At implant, preferably within 15 days of enrollment
description: "Excitable myocardium areas" are areas that can be paced by the implanted Axone 4LV lead.
measure: Effect of CRT therapy, in particular bizone pacing, on QRS parameters, at discharge and 6 months post implant
time frame: At discharge, within 7 days of implant, and at 6 months
description: The effect of monozone and bizone CRT pacing on duration of QRS is measured in milliseconds.
measure: Effect of CRT therapy, in particular bizone pacing, on Left Pre-Ejection Interval (LPEI), at discharge
time frame: At discharge, within 7 days of implant
description: LPEI (in milliseconds) is an electromechanical parameter that can be assessed using echocardiography.
measure: Axone 4LV lead pacing threshold
time frame: Discharge (within 7 days of implant), 6 weeks, 3 months, 6 months, 12 months, 24 months 36 months, 48 months
description: Pacing threshold is measured in Volts.
measure: Axone 4LV lead pacing impedance
time frame: Discharge (within 7 days of implant), 6 weeks, 3 months, 6 months, 12 months, 24 months 36 months, 48 months
description: Pacing impedance is measured in Ohms.
measure: Presence of phrenic nerve stimulation (PNS) with the Axone 4LV lead
time frame: Implant (preferably within 15 days of enrollment), discharge (within 7 days of implant), 6 weeks, 3 months, 6 months
description: The presence of PNS will be assessed at 10V using an external pacing system analyzer at implant, or at pacing threshold +2V at other visits.
measure: Axone 4LV lead programming
time frame: Discharge (within 7 days of implant), 6 weeks, 3 months, 6 months, 12 months, 24 months 36 months, 48 months
description: Lead programming will be reported using: (i) pacing amplitude (Volts), pulse width (milliseconds) and pacing vector(s) selected.
measure: Energy consumption associated with Axone 4LV lead
time frame: 6 months
description: Energy will be calculated using the formula: E=(pacing amplitude^2 x pulse width)/impedance. Energy, pacing amplitude, pulse width and impedance are measured in Joules, Volts, milliseconds, and Ohms, respectively.
measure: Axone system-related annual complication-free rate
time frame: 12 months, 24 months 36 months, 48 months
description: Definition of Axone system related complication is the same as for primary safety endpoint.
measure: Clinical response to CRT at 12 months post implant
time frame: 12 months
description: Clinical response will be determined by looking at functional improvement, reverse remodelling, freedom from heart failure events, and rate of non-responders:
(i) functional improvement is defined as improvement in ≥1 NYHA (New York Heart Association) class from baseline to 12 months.
(ii) reverse remodelling is a ≥12% increase in left ventricular end systolic volume index (LVESVi: LVESV [mL] and body surface area [m^2] will be combined to report LVESVi).
(iii) freedom from heart failure events is defined as an absence of death or HF hospitalization.
(iv) non-responders are all those who are not responders. A responder is defined as a subject that is not dead and who did not experience any HF hospitalization and that has a stable or improved NYHA class versus baseline.
arm group label: Axone 4LV Lead
arm group type: Experimental
description: Subjects implanted with the Axone 4LV Lead
intervention type: Device
intervention name: Implantation of the Axone 4LV Lead
description: Implantation of the Axone 4LV Lead
arm group label: Axone 4LV Lead
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Frédéric Anselme, MD
role: Principal Investigator
affiliation: CHU de Rouen, France
last name: Anaïs Balland, MSc
phone: +33602000014
email: anais.balland@crm.microport.com
facility: 
status: Recruiting
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status: Not yet recruiting
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status: Recruiting
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status: Recruiting
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status: Not yet recruiting
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status: Recruiting
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status: Recruiting
investigator: 
country: Austria
country: France
country: Germany
country: Italy
country: Netherlands
country: Portugal
country: Spain
citation: Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, Falk V, Gonzalez-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GMC, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P; ESC Scientific Document Group. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016 Jul 14;37(27):2129-2200. doi: 10.1093/eurheartj/ehw128. Epub 2016 May 20. No abstract available. Erratum In: Eur Heart J. 2016 Dec 30;:
PMID: 27206819
citation: Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, Tavazzi L; Cardiac Resynchronization-Heart Failure (CARE-HF) Study Investigators. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005 Apr 14;352(15):1539-49. doi: 10.1056/NEJMoa050496. Epub 2005 Mar 7.
PMID: 15753115
citation: Linde C, Abraham WT, Gold MR, St John Sutton M, Ghio S, Daubert C; REVERSE (REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction) Study Group. Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. J Am Coll Cardiol. 2008 Dec 2;52(23):1834-1843. doi: 10.1016/j.jacc.2008.08.027. Epub 2008 Nov 7.
PMID: 19038680
citation: Zeitler EP, Friedman DJ, Daubert JP, Al-Khatib SM, Solomon SD, Biton Y, McNitt S, Zareba W, Moss AJ, Kutyifa V. Multiple Comorbidities and Response to Cardiac Resynchronization Therapy: MADIT-CRT Long-Term Follow-Up. J Am Coll Cardiol. 2017 May 16;69(19):2369-2379. doi: 10.1016/j.jacc.2017.03.531.
PMID: 28494974
citation: Healey JS, Hohnloser SH, Exner DV, Birnie DH, Parkash R, Connolly SJ, Krahn AD, Simpson CS, Thibault B, Basta M, Philippon F, Dorian P, Nair GM, Sivakumaran S, Yetisir E, Wells GA, Tang AS; RAFT Investigators. Cardiac resynchronization therapy in patients with permanent atrial fibrillation: results from the Resynchronization for Ambulatory Heart Failure Trial (RAFT). Circ Heart Fail. 2012 Sep 1;5(5):566-70. doi: 10.1161/CIRCHEARTFAILURE.112.968867. Epub 2012 Aug 14.
PMID: 22896584
citation: Daubert C, Behar N, Martins RP, Mabo P, Leclercq C. Avoiding non-responders to cardiac resynchronization therapy: a practical guide. Eur Heart J. 2017 May 14;38(19):1463-1472. doi: 10.1093/eurheartj/ehw270.
PMID: 27371720
citation: Okamura H. Up-to-date cardiac resynchronization therapy. J Gen Fam Med. 2017 May 17;18(5):195-199. doi: 10.1002/jgf2.24. eCollection 2017 Oct.
PMID: 29264026
citation: Macias A, Gavira JJ, Alegria E, Azcarate PM, Barba J, Garcia-Bolao I. [Effect of the left ventricular pacing site on echocardiographic parameters of ventricular dyssynchrony in patients receiving cardiac resynchronization therapy]. Rev Esp Cardiol. 2004 Feb;57(2):138-45. Spanish.
PMID: 14967109
citation: Butter C, Auricchio A, Stellbrink C, Fleck E, Ding J, Yu Y, Huvelle E, Spinelli J; Pacing Therapy for Chronic Heart Failure II Study Group. Effect of resynchronization therapy stimulation site on the systolic function of heart failure patients. Circulation. 2001 Dec 18;104(25):3026-9. doi: 10.1161/hc5001.102229.
PMID: 11748094
citation: Umar F, Taylor RJ, Stegemann B, Marshall H, Flannigan S, Lencioni M, De Bono J, Griffith M, Leyva F. Haemodynamic effects of cardiac resynchronization therapy using single-vein, three-pole, multipoint left ventricular pacing in patients with ischaemic cardiomyopathy and a left ventricular free wall scar: the MAESTRO study. Europace. 2016 Aug;18(8):1227-34. doi: 10.1093/europace/euv396. Epub 2015 Dec 30.
PMID: 26718535
citation: Bonadei I, Vizzardi E, Gorga E, Carubelli V, Pagnoni M, Sciatti E, Raweh A, Cerini M, Bontempi L, Curnis A, Metra M. Role of the old and new echocardiographic technologies in cardiac resynchronization therapy. Minerva Cardioangiol. 2016 Oct;64(5):572-80. Epub 2015 Jun 23.
PMID: 26099222
citation: O'Brien T, Park MS, Youn JC, Chung ES. The Past, Present and Future of Cardiac Resynchronization Therapy. Korean Circ J. 2019 May;49(5):384-399. doi: 10.4070/kcj.2019.0114.
PMID: 31074211
citation: Leclercq C, Burri H, Curnis A, Delnoy PP, Rinaldi CA, Sperzel J, Lee K, Calo L, Vicentini A, Concha JF, Thibault B. Cardiac resynchronization therapy non-responder to responder conversion rate in the more response to cardiac resynchronization therapy with MultiPoint Pacing (MORE-CRT MPP) study: results from Phase I. Eur Heart J. 2019 Sep 14;40(35):2979-2987. doi: 10.1093/eurheartj/ehz109.
PMID: 30859220
citation: Auricchio A, Heggermont WA. Technology Advances to Improve Response to Cardiac Resynchronization Therapy: What Clinicians Should Know. Rev Esp Cardiol (Engl Ed). 2018 Jun;71(6):477-484. doi: 10.1016/j.rec.2018.01.006. Epub 2018 Feb 14. English, Spanish.
PMID: 29454549
citation: Antoniadis AP, Behar JM, Sieniewicz B, Gould J, Niederer S, Rinaldi CA. A comparison of the different features of quadripolar left ventricular pacing leads to deliver cardiac resynchronization therapy. Expert Rev Med Devices. 2017 Sep;14(9):697-706. doi: 10.1080/17434440.2017.1369404. Epub 2017 Aug 23.
PMID: 28835138
citation: Tomassoni G, Baker J, Corbisiero R, Love C, Martin D, Niazi I, Sheppard R, Worley S, Beau S, Greer GS, Aryana A, Cao M, Harbert N, Zhang S; Promote(R) Q CRT-D and Quartet(R) Left Ventricular Heart Lead Study Group. Postoperative performance of the Quartet(R) left ventricular heart lead. J Cardiovasc Electrophysiol. 2013 Apr;24(4):449-56. doi: 10.1111/jce.12065. Epub 2013 Jan 22.
PMID: 23339555
citation: Crossley GH, Biffi M, Johnson B, Lin A, Gras D, Hussin A, Cuffio A, Collier JL, El-Chami M, Li S, Holloman K, Exner DV. Performance of a novel left ventricular lead with short bipolar spacing for cardiac resynchronization therapy: primary results of the Attain Performa quadripolar left ventricular lead study. Heart Rhythm. 2015 Apr;12(4):751-8. doi: 10.1016/j.hrthm.2014.12.019. Epub 2014 Dec 19.
PMID: 25533587
citation: Mittal S, Nair D, Padanilam BJ, Ciuffo A, Gupta N, Gallagher P, Goldner B, Hammill EF, Wold N, Stein K, Burke M. Performance of Anatomically Designed Quadripolar Left Ventricular Leads: Results from the NAVIGATE X4 Clinical Trial. J Cardiovasc Electrophysiol. 2016 Oct;27(10):1199-1205. doi: 10.1111/jce.13044. Epub 2016 Aug 19.
PMID: 27434039
responsible party type: Sponsor
mesh term: Heart Failure
sharing ipd: No