Improving CRT Outcome With Non-Invasive Cardiac Mapping (ICONIC-M)

ICONIC-M: Improving CRT Outcome With Non-Invasive Cardiac Mapping. A Multicenter Randomized Controlled Study To Assess Patient Response to CRT Comparing ECGI Map Guided Left Ventricular Lead Placement With Empirical Lead Placement

The ICONIC-M study is a multicenter randomized controlled study to assess patient response to CRT comparing ECGI map guided left ventricular lead placement with empirical lead placement.

The hypothesis of the investigation is to demonstrate that CRT LV lead implantation guided by a map obtained with the Amycard 01C System and showing LV Latest Electrical Activated Site (LEAS) in combination with a CT cardiac venogram improves CRT outcome. An improved CRT outcome is defined as a ≥30% increase in LVESVi reduction compared to empiric CRT LV lead implantation.

The sample size will be 136 in the Control arm and 194 in the Active arm. A total of 330 subjects.

The study follows an adaptive design, in where one interim analysis at 70% enrollment will be performed. The sponsor may stop enrollment when either one of the following conditions apply:

• Statistical significant difference between groups in the primary endpoint has been reached confirming a difference in reduction of the LVESVi of ≥30% in the Active arm compared to the Control arm
• There is no trend or reason to believe statistical significance will be reached with a higher sample size.

Statistical significance (primary endpoint) is reached at interim (70%) or at total (100%) of enrollment with a significance value P lower than 0.025.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure With Reduced Ejection Fraction
• Intervention / Treatment: Device: Post-implantation assessment; Device: Pre-implantation planning

Detailed Description

The study is conducted at European sites as a Post-Market Clinical Follow-Up study of a CE marked device (Amycard 01C). Its aim is to strengthen clinical evidence by assessing whether the use of this device for CRT planning improves clinical outcome in a statistically significant number of patients.

• Study Type: Interventional
• Enrollment (Estimated): 330
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Matthias Egger, PhD; Phone Number: +41 78 659 22 75; Email: matthias.egger@ep-solutions.ch
• Study Contact Backup: Name: Christelle Gakuba; Email: christelle.gakuba@ep-solutions.ch

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Amsterdam University Medical Center
    • Contact: Cornelius Allaart, Dr
  • Groningen, Netherlands
    • Groningen University Medical Center
    • Contact: Alexander Maas, Dr
  • Maastricht, Netherlands
    • Maastricht University Hospital
    • Contact: Twan van Stipdonk, Dr
  • Utrecht, Netherlands
    • Utrecht University Medical Center
    • Contact: Mathias Meine, Dr
• Portugal
  • Lisbon, Portugal
    • Hospital da Luz
    • Contact: Ana Leonor Parreira, Dra
• Sweden
  • Lund, Sweden
    • Lund University Hospital
    • Contact: Rasmus Borgquist, Dr
  • Stockholm, Sweden
    • Karolinska University Hospital
• United Kingdom
  • London, United Kingdom
    • King's College
  • London, United Kingdom
    • Bart's Hospital
    • Contact: Pier Lambiase, Dr
  • Oxford, United Kingdom
    • Oxford University Hospital
    • Contact: Tim Betts, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Appropriately signed and dated informed consent.
2. Age ≥18 years at time of consent.
3. Received optimal medical therapy for HF for at least 3 months before screening
4. Patient in sinus rhythm at the time of screening fulfilling Class I or IIa criteria per ESC CRT guidelines 2013 .
5. Patient is intended for placement of a CRT device with biventricular (BiV) pacing.

Exclusion Criteria:

1. Previous cardiac pacemaker/CRT/ICD implantation
2. Acute diseases or exacerbations of chronic diseases (as per the investigator's discretion)
3. Contraindications to CT scanning
4. Contraindications to body surface ECG mapping: (ongoing wound healing on the chest (e.g. recent surgery), skin diseases, allergic reactions to surface mapping electrodes and medical band-aid)
5. Pregnant, or subjects planning to become pregnant within 6 months after signing informed consent (a documented negative pregnancy test (serum or blood) is required for women of childbearing potential)
6. Incapacitated individuals, defined as persons who are mentally ill, mentally handicapped, or individuals without legal authority, are excluded from the study population

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control; The CRT device is implanted according to clinical practice, without pre-implantation planning. The outcome of the procedure is assessed via echography as per clinical practice. In addition to clinical practice, the subjects are required to fill in a quality-of-life questionnaire and are subject to an ECG mapping procedure with the Amycard 01C device, including non-contrast CT, to assess the distance between left ventricular lead placement and the latest electrical activation site in the absence of planning information.	Device: Post-implantation assessment; ECGi mapping using the CE marked Amycard 01C device and a non-contrast CT; Other Names: ECGI mapping
Experimental: Active; A pre-implantation ECG mapping with the Amycard 01C device, including CT, is performed prior to the CRT device implantation. The resulting target area for the left ventricular lead placement is communicated to the implanting physician, who will attempt to reach a point close to the target, using the available venous access. At six-month follow-up, response to the therapy is assessed using echocardiography, and a second ECG mapping with Amycard 01C is performed, to assess the distance between actual implantation site and target in the presence of pre-implantation planning information.	Device: Post-implantation assessment; ECGi mapping using the CE marked Amycard 01C device and a non-contrast CT; Other Names: ECGI mapping; Device: Pre-implantation planning; ECGi mapping using the CE marked Amycard 01C device and a contrast enhanced CT; Other Names: ECGI mapping

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of left ventricular end-systolic volume index (LVESVi)	Reduction versus baseline of LVESVi as measured by transthoracic echocardiography	6 months post CRT implantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successfully placed LV leads	Rate of successfully placed LV leads in the control and active arms	6 months post CRT implantation
Correctly predicted distance between latest activation site and LV lead	Rate of correctly predicted distance between the latest electrical activation site, as identified with Amycard 01C, and the LV lead, as identified on CT	6 months post implantation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Composite Score	Clinical composite score consisting of Quality of life questionnaire, mortality rate and heart failure hospitalization rate	6 months post CRT implantation
ECGi acquisition procedural failure rate	Rate of unsuccessful ECGi mapping procedures using the Amycard 01C device	6 months post CRT implantation
Subgroup analysis	Subgroup analysis including stratification based on various conditions or habits (ischemia, diabetes, smoking, pulmonary disease, impaired right ventricular function, etc)	6 months post CRT implantation
Shift of Latest Electrical Activation Site	Degree of shift of the latest electrical activation site, as identified using the Amycard 01C device, between baseline and the six-months follow-up	6 months post CRT implantation

Collaborators and Investigators

• Sponsor: EP Solutions SA
• Investigators: Principal Investigator: Niraj Varma, Prof., The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: September 29, 2022
• First Submitted That Met QC Criteria: September 29, 2022
• First Posted (Actual): October 4, 2022

Study Record Updates

• Last Update Posted (Actual): September 7, 2023
• Last Update Submitted That Met QC Criteria: September 6, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Cardiac Resynchronization Therapy; Left Bundle Branch Block
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: DCR013-22

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No