Clinical trial NCT04463641: Assessment of the Axone Micro Quadripolar Lead for Enhanced Cardiac Resynchronization Therapy
Official title: Assessment of the Axone Micro Quadripolar Lead for Enhanced Cardiac Resynchronization Therapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Heart Failure
Cardiac Resynchronization Therapy
Keywords: Left Ventricular Lead
Lead sponsor: MicroPort CRM
Sponsor class: INDUSTRY
First posted: 2020-07-09
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to assess the chronic safety and performance of the Axone left ventricular (LV) micro-lead.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Indication for cardiac resynchronization therapy-defibrillator (CRT-D) device implant according to the latest ESC (European Society of Cardiology) guidelines
* De-novo implant of a Platinium 4LV CRT-D device (or any newer 4LV CRT-D model manufactured by MicroPort CRM)
* Reviewed, signed and dated informed consent form

Exclusion Criteria:

* LV lead previous implant attempt
* Upgrade to CRT from a previously implanted pacemaker or implantable cardioverter-defibrillator (ICD), or CRT device replacement
* Known allergy to contrast media used for imaging during cardiac catheterization
* Tricuspid valvular disease or any type of tricuspid replacement heart valve (mechanical or tissue)
* Severe renal failure (creatinine clearance according to the Modification of Diet in Renal Disease (MDRD) formula \< 30ml/min/m²)
* Active myocarditis
* Stroke, myocardial infarction or cardiac revascularization within 40 days prior to implant
* Previous heart transplant or currently on heart transplant list
* Life expectancy less than 1 year
* Already included in another clinical study that could confound the results of this study
* Pre-menopausal women / women in childbearing age, including pregnant and breastfeeding women
* Less than 18 years old or under guardianship
* Incapacitated subject, inability to understand the purpose of the study, or to meet follow-up visits at the implanting site as defined in the protocol
* Diagnosis of drug addiction (substance use disorder)

Primary outcomes:
measure: Safety co-primary endpoint, defined as Axone system related complication free rate at 6 months post implant
timeFrame: 6 months
measure: Performance co-primary endpoint, defined as LV pacing success rate at 6 months post implant
timeFrame: 6 months
Secondary outcomes:
measure: Bizone LV pacing success rate at 6 months post implant
timeFrame: 6 months
Other outcomes:
measure: Axone 4LV implantation success rate
timeFrame: At implant, preferably within 15 days of enrollment
measure: Implantation duration
timeFrame: At implant, preferably within 15 days of enrollment
measure: Fluoroscopy time
timeFrame: At implant, preferably within 15 days of enrollment
measure: Fluoroscopy dose
timeFrame: At implant, preferably within 15 days of enrollment
measure: Axone system handling assessment
timeFrame: At implant, preferably within 15 days of enrollment
measure: Axone implanters' learning curve
timeFrame: At implant, preferably within 15 days of enrollment
measure: Number of excitable myocardium areas at implant
timeFrame: At implant, preferably within 15 days of enrollment
measure: Effect of CRT therapy, in particular bizone pacing, on QRS parameters, at discharge and 6 months post implant
timeFrame: At discharge, within 7 days of implant, and at 6 months
measure: Effect of CRT therapy, in particular bizone pacing, on Left Pre-Ejection Interval (LPEI), at discharge
timeFrame: At discharge, within 7 days of implant
measure: Axone 4LV lead pacing threshold
timeFrame: Discharge (within 7 days of implant), 6 weeks, 3 months, 6 months, 12 months, 24 months 36 months, 48 months
measure: Axone 4LV lead pacing impedance
timeFrame: Discharge (within 7 days of implant), 6 weeks, 3 months, 6 months, 12 months, 24 months 36 months, 48 months
measure: Presence of phrenic nerve stimulation (PNS) with the Axone 4LV lead
timeFrame: Implant (preferably within 15 days of enrollment), discharge (within 7 days of implant), 6 weeks, 3 months, 6 months
measure: Axone 4LV lead programming
timeFrame: Discharge (within 7 days of implant), 6 weeks, 3 months, 6 months, 12 months, 24 months 36 months, 48 months
measure: Energy consumption associated with Axone 4LV lead
timeFrame: 6 months
measure: Axone system-related annual complication-free rate
timeFrame: 12 months, 24 months 36 months, 48 months
measure: Clinical response to CRT at 12 months post implant
timeFrame: 12 months
Locations:
city: Linz
country: Austria
facility: Kepler Universitätsklinikum
city: Annecy
country: France
facility: CH Annecy Genevois
city: Chambray-lès-Tours
country: France
facility: CHRU Hopital Trousseau
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand
city: Grenoble
country: France
facility: CHU Grenoble
city: Lille
country: France
facility: CHRU de Lille - Hôpital Cardiologique
city: Rennes
country: France
facility: CHU Pontchaillou
city: Rouen
country: France
facility: CHU de Rouen
city: Toulouse
country: France
facility: CHU Toulouse
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg Eppendorf
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein Campus Kiel
city: Brescia
country: Italy
facility: ASST Spedali Civili di Brescia
city: Naples
country: Italy
facility: Ospedale Pellegrini
city: Naples
country: Italy
facility: Ospedale Policlinico Federico II
city: Zwolle
country: Netherlands
facility: Isala Klinieken
city: Lisbon
country: Portugal
facility: Centro Hospitalar Universitário Lisboa Norte - Hospital de Santa Maria
city: Porto
country: Portugal
facility: Centro Hospitalar Universitário do Porto
city: Alicante
country: Spain
facility: Hospital Universitario General de Alicante
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Vigo
country: Spain
facility: Hospital Álvaro Cunqueiro
Study officials:
affiliation: CHU de Rouen, France
name: Frédéric Anselme, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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: 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.
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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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.