Pulsed Field Ablation and Pulsed Field CRyoAbLation in PErsistent AtriaL FibrilLation (PARALELL)

PARALELL - Pulsed Field Ablation and Pulsed Field CRyoAbLation in PErsistent AtriaL FibrilLation

A prospective, two-arm, multi-center, randomized, open-label, pre-market, First-in-Human clinical study designed to provide safety and performance data regarding the use of the Adagio PFA and PFCA Systems in the treatment of PsAF.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Device: Atrial ablation for subject scheduled for a de novo endocardial ablation of symptomatic, drug-refractory PsAF.

Detailed Description

Enrolled subjects will be treated (ablation) with the Adagio PFA or PFCA System in a 1:1 randomized fashion.

Treatment will include the isolation of pulmonary veins (PVIs), and isolation of the left atrial posterior wall (PWI), and CTI at the discretion and clinical judgment of the investigator.

Data will be collected throughout 12-month follow up period to assess safety and performance of the device. Recurrence of atrial arrhythmias is measured by 12-lead ECGs and 48-hour continuous ECG recording (Holter).

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nabil Jubran; Phone Number: 9493481188; Email: njubran@adagiomedical.com
• Study Contact Backup: Name: Doug Kurschinski; Phone Number: 9493481188; Email: dkurschinski@adagiomedical.com

Study Locations

• Belgium
  • Aalst, Belgium, B-9300
    • Recruiting
    • Onze-Lieve-Vrouwziekenhuis (OLV)
    • Contact: Tom De Potter, M.D.; Email: tom.de.potter@olvz-aalst.be
    • Principal Investigator: Tom De Potter, M.D.
• Canada
  • Quebec
    • Montréal, Quebec, Canada, H3G 1A4
      • Recruiting
      • McGill University Health Centre (MUHC), Montreal General Hospital (MGH)
      • Contact: Atul Verma, MD
      • Principal Investigator: Atul Verma, MD
• Czechia
  • Prague, Czechia, 150 30
    • Recruiting
    • Nemocnice Na Homolce
    • Contact: Petr Neuzil, M.D.; Email: petr.neuzil@homolka.cz
    • Principal Investigator: Petr Neuzil, M.D.
• Ireland
  • Dublin, Ireland, A94 E4X7
    • Recruiting
    • Blackrock Health
    • Contact: David Keane, M.D.; Email: dkeane@svhg.ie
    • Principal Investigator: David Keane, M.D.
• Netherlands
  • Nieuwegein, Netherlands, 3435
    • Recruiting
    • St Antonius Ziekenhuis
    • Contact: Lucas Boersma, Prof
    • Principal Investigator: Lucas Boersma, Professor
• United Kingdom
  • London, United Kingdom, SW17 0QT
    • Recruiting
    • St George'S University Hospital
    • Contact: Mark Gallagher, M.D.; Email: mark.gallagher@stgeorges.nhs.uk
    • Principal Investigator: Mark Gallagher, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

IC 1 Male or female between the ages of 18 - 80 years

IC 2 Currently scheduled for an ablation of symptomatic persistent (> 7 days) atrial fibrillation within the past year documented by ECG or Continuous Holter monitoring

IC 3 Refractory to at least one class I or III AAD. (Refractory defined as not effective or not tolerated)

IC 4 Willingness, ability, and commitment to participate in baseline and follow-up evaluations for the full length of the study

IC 5 Willingness and ability to give an informed consent

Exclusion Criteria:

EC 1 In the opinion of the Investigator, any known contraindication to an atrial ablation, TEE, or anticoagulation. Including but not limited to the identification of any atrial thrombus or evidence of sepsis

EC 2 Continuous AF lasting longer than 12-months

EC 3 History of previous left atrial ablation or surgical treatment for AF/AFL/AT

EC 4 AF secondary to electrolyte imbalance, active thyroid disease, or any other reversible or non-cardiac cause

EC 5 Structural heart disease as described below:

1. Left ventricular ejection fraction (LVEF) < 40% based on most recent TTE
2. Left atrial size > 55 mm (parasternal long axis view) documented within 6-months of screening
3. NYHA Class III or IV heart failure documented within the previous 12-months
4. An implanted pacemaker or ICD
5. Previous cardiac surgery, ventriculotomy, or atriotomy (excluding atriotomy for CABG),
6. Previous cardiac valvular surgical or percutaneous procedure, or prosthetic valve
7. Interatrial baffle, closure device, patch, or PFO occluder
8. Presence of a left atrial appendage occlusion device
9. Presence of any pulmonary vein stenting devices
10. Coronary artery bypass graft (CABG) or PTCA procedure within six (6) months prior to procedure
11. Unstable angina or ongoing myocardial ischemia
12. Myocardial infarction within the previous six (6) months prior to procedure
13. Moderate or severe mitral insufficiency or stenosis based on most recent TTE
14. Atrial myxoma
15. Significant congenital anomaly

EC 6 BMI > 40

EC 7 Any previous history of cryoglobulinemia (for those patients randomized to the PFCA arm)

EC 8 History of blood clotting or bleeding disease

EC 9 History of severe COPD requiring steroid use in the previous 12-months

EC 10 History of severe sleep apnea (AHI > 30) not currently treated with a CPAP machine or other mechanical device

EC 11 Stroke or TIA within the last year.

EC 12 Any prior history or current evidence of hemidiaphragmatic paralysis

EC 13 Pregnant or lactating (current or anticipated during study follow-up

EC 14 Current enrollment in any other study protocol where testing or results from that study may interfere with the procedure or outcome measurements for this study

EC 15 Any other conditions such as, mental illness, addictive disease, terminal illness with a life expectancy of less than two years, extensive travel away from the research center that may lead to non-compliance with the protocol procedure or follow up

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pulsed Field Ablation (PFA) group; PsAF patients treated by PFA	Device: Atrial ablation for subject scheduled for a de novo endocardial ablation of symptomatic, drug-refractory PsAF.; Treatment will include the isolation of pulmonary veins (PVIs), and isolation of the left atrial posterior wall (PWI). A right atrial cavo-tricuspid line for bi-directional block may be performed at discretion and clinical judgment of the investigator
Experimental: Pulsed Field CryoAblation (PFCA) group; PsAF patients treated by PFCA	Device: Atrial ablation for subject scheduled for a de novo endocardial ablation of symptomatic, drug-refractory PsAF.; Treatment will include the isolation of pulmonary veins (PVIs), and isolation of the left atrial posterior wall (PWI). A right atrial cavo-tricuspid line for bi-directional block may be performed at discretion and clinical judgment of the investigator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Endpoint for Safety	Analysis of the proportion of subjects who are free from device/procedure-related Major Adverse Events that occur during or following the ablation procedure	Up to 7 days following the ablation procedure
Primary Procedural Performance Outcome	Analysis of the evidence of procedural electrical isolation of all pulmonary veins, posterior wall, and bidirectional block (if applicable) across all other ablation lines using the study device.	Procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
One-Year Safety	Recording and analysis of all identified serious adverse events and serious adverse device effects through 12 months post-procedure.	12 months
One-Year Performance	Proportion of subjects receiving a single ablation procedure who has freedom from any documented left atrial arrhythmia (AF/AFL/AT) lasting longer than 30 seconds following the Blanking Period (3-months ± 14-days post index ablation) using a continuous 48-hour ECG recording through 12 months post-procedure.	12 months
Procedural Performance - ablation time	Ablation time defined as the total time for energy delivery to achieve PVI, PWI, and CTI (if applicable)	procedure
Procedural Performance - procedure time	Total procedure time defined as the time from first venous access to the removal of the catheters from the heart at the end of the procedure	procedure
Procedural Performance - fluoroscopy time	Procedure fluoroscopy time	procedure
Procedural Performance - intraprocedural PV reconnection rate	The rate of intraprocedural PV reconnection - defined as confirmed conduction across a PVI line during the 20-minute waiting period to confirm PVI	procedure
Procedural Performance - AAD use	Recording of the use of AADs in the follow up period beyond a 90-day blanking period	procedure and up to 12-month
Procedural Performance - repeat ablation	Number of repeat ablations within and following the blanking period	procedure and up to 12-month

Collaborators and Investigators

• Sponsor: Adagio Medical
• Investigators: Principal Investigator: Atul Verma, MD, McGill University Health Centre; Montreal, Canada

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2022
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: June 2, 2022
• First Submitted That Met QC Criteria: June 6, 2022
• First Posted (Actual): June 7, 2022

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: AF; Persistent AF; PFA; Pulsed Field Ablation; Pulsed Field CryoAblation; PFCA; Adagio Medical
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: CS-169

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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