Pulsed Field Ablation for Atrial Fibrillation

(PARALELL Trial)

Not currently recruiting at 6 trial locations

Overseen By Doug Kurschinski

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Adagio Medical

Disqualifiers: Structural heart disease, BMI > 40, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Procedure

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two new treatments for individuals with persistent atrial fibrillation, a long-term irregular heartbeat. The goal is to assess the safety and effectiveness of the Adagio PFA and PFCA Systems in managing this condition. Participants will be divided into two groups: one will receive Pulsed Field Ablation, and the other will receive Pulsed Field CryoAblation. Suitable candidates have experienced atrial fibrillation for over a week, despite trying at least one medication that was ineffective or caused issues. As an unphased trial, this study provides a unique opportunity to contribute to medical research and potentially benefit from cutting-edge treatments.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the trial involves ablation for atrial fibrillation, it's possible that some medications might need to be adjusted. Please consult with the trial team for specific guidance.

What prior data suggests that the Adagio PFA and PFCA Systems are safe for treating PsAF?

Studies have shown that pulsed field ablation (PFA) is generally safe for patients with atrial fibrillation, an irregular heartbeat. A review of multiple studies found that PFA is well-tolerated, with few complications, indicating that serious side effects are rare.

Research also indicates that pulsed field cryoablation (PFCA) is safe. An initial study on PFCA showed that patients managed the procedure well, with safety results similar to other ablation methods.

Both treatments have undergone testing in early human trials. While more research is ongoing, current evidence suggests they are safe options for managing atrial fibrillation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Pulsed Field Ablation (PFA) and Pulsed Field CryoAblation (PFCA) for atrial fibrillation because these methods promise a new way to treat this heart condition. Unlike traditional ablation, which uses heat or cold to destroy problematic heart tissue, PFA and PFCA use electric fields to selectively target and disrupt the cells causing the arrhythmia, potentially reducing damage to surrounding healthy tissue. This precision could lead to fewer side effects and a quicker recovery for patients. Additionally, the unique approach of these systems may offer more consistent results compared to current methods, making them a promising alternative for managing atrial fibrillation.

What evidence suggests that the Adagio PFA and PFCA Systems could be effective for treating PsAF?

Research has shown that pulsed field ablation (PFA) holds promise for treating atrial fibrillation (AF), a condition characterized by irregular heartbeats. One study found that 82% of patients remained free from AF after a single PFA procedure within a year, demonstrating its effectiveness in reducing AF episodes. In this trial, some participants will receive PFA.

Pulsed field cryoablation (PFCA) is another treatment under study in this trial. Early results suggest it is also effective for treating AF, similar to PFA. Both treatments aim to safely and effectively reduce irregular heartbeats in patients with ongoing AF. ^{1 6 7 8 9}

Who Is on the Research Team?

Atul Verma, MD

Principal Investigator

McGill University Health Centre; Montreal, Canada

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with symptomatic, drug-resistant persistent atrial fibrillation (lasting over 7 days but less than a year). Participants must be scheduled for an ablation procedure and have failed at least one antiarrhythmic drug. Exclusions include severe heart conditions, previous ablations or cardiac surgeries, clotting disorders, extreme obesity (BMI > 40), and other health issues that could affect the study.

Inclusion Criteria

I am willing and able to give my consent for treatment.

I am scheduled for a procedure to treat my persistent atrial fibrillation that has lasted more than 7 days.

I am willing and able to follow the study's requirements.

Exclusion Criteria

You have a very high body mass index (BMI).

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

I have severe sleep apnea not treated with a machine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo ablation treatment with the Adagio PFA or PFCA System, including isolation of pulmonary veins and left atrial posterior wall

Procedure

Blinding Period

A 3-month period post-ablation where arrhythmia recurrence is not assessed

3 months

Follow-up

Participants are monitored for safety and performance of the device, with assessments including 12-lead ECGs and 48-hour continuous ECG recording

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Adagio PFA and PFCA Systems

Trial Overview The study compares two systems: Adagio PFA and PFCA in treating persistent atrial fibrillation. It's a first-in-human trial to assess safety and performance of these new ablation technologies. Patients will be randomly assigned to either treatment arm in multiple centers.

How Is the Trial Designed?

Group I: Pulsed Field CryoAblation (PFCA) group Experimental Treatment 1 Intervention

PsAF patients treated by PFCA

Group II: Pulsed Field Ablation (PFA) group Experimental Treatment 1 Intervention

PsAF patients treated by PFA

Adagio PFA and PFCA Systems is already approved in European Union, United States for the following indications:

Approved in European Union as Adagio iCLAS for:

• Paroxysmal atrial fibrillation
• Persistent atrial fibrillation
• Atrial flutter

Approved in United States as Adagio CryoPulse for:

• Under investigation for persistent atrial fibrillation

Who Is Running the Clinical Trial?

Adagio Medical

Lead Sponsor

Trials

8

Recruited

930+

Published Research Related to This Trial

In a study of 200 patients with paroxysmal atrial fibrillation, pulsed-field ablation (PFA) demonstrated a high rate of freedom from atrial tachyarrhythmia recurrence at 1 year (85.0%), comparable to cryoballoon ablation (CBA) and radiofrequency ablation (RFA).

PFA procedures were efficient, with a median procedure time of 94 minutes, which is shorter than RFA (182 minutes) but longer than CBA (75 minutes), indicating that PFA is a safe and effective option for pulmonary vein isolation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulsed-field vs. cryoballoon vs. radiofrequency ablation: a propensity score matched comparison of one-year outcomes after pulmonary vein isolation in patients with paroxysmal atrial fibrillation. Maurhofer, J., Kueffer, T., Madaffari, A., et al.[2023]

In a study of 1568 patients undergoing pulsed field ablation (PFA) for atrial fibrillation (AF), both male and female patients showed similar rates of freedom from atrial arrhythmia after one year, indicating comparable effectiveness of the treatment across sexes.

The safety profile was also similar, with no significant differences in acute major adverse events between male (1.5%) and female (2.5%) patients, suggesting that PFA is a safe option for both genders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes by Sex After Pulsed Field Ablation of Atrial Fibrillation. Turagam, MK., Neuzil, P., Schmidt, B., et al.[2023]

Pulsed-field ablation (PFA) effectively achieved pulmonary vein isolation (PVI) in all 80 pulmonary veins of 20 patients, demonstrating its efficacy in treating atrial fibrillation.

UHDx mapping revealed that PFA creates wide and durable lesions with significant voltage reduction, although early reconnection of pulmonary veins can occur in a small percentage of cases (6.25%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulsed-field ablation combined with ultrahigh-density mapping in patients undergoing catheter ablation for atrial fibrillation: Practical and electrophysiological considerations. Gunawardene, MA., Schaeffer, BN., Jularic, M., et al.[2022]

Pulsed field ablation (PFA) using the CENTAURI System achieved 100% pulmonary vein isolation in 82 patients with atrial fibrillation, demonstrating high efficacy with a first-pass isolation rate of 92.2%.

The study reported a favorable safety profile, with only four serious adverse events, indicating that optimized PFA is a viable and safe treatment option for atrial fibrillation when integrated with existing ablation techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulsed field ablation using focal contact force-sensing catheters for treatment of atrial fibrillation: acute and 90-day invasive remapping results. Anić, A., Phlips, T., Brešković, T., et al.[2023]

In a study of 181 patients with atrial fibrillation, pulsed-field ablation (PFA) and cryoballoon (CB) ablation showed similar procedural times and complication rates, indicating comparable safety profiles for both techniques.

After a median follow-up of 404 days, the rates of atrial fibrillation recurrence were also similar between the PFA and CB groups, suggesting that both methods are equally effective for maintaining sinus rhythm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pulmonary vein isolation with pulsed field ablation vs. novel cryoballoon ablation system for atrial fibrillation. Badertscher, P., Weidlich, S., Knecht, S., et al.[2023]

In a study involving eight healthy pigs, pulsed-field ablation (PFA) demonstrated effective and durable isolation of pulmonary veins without causing damage to surrounding tissues, even when performed in challenging locations.

Histological analysis confirmed complete cell death around the ablated areas after 30 days, indicating that PFA could be a safer alternative to traditional ablation methods like radiofrequency and cryoablation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo porcine characterization of atrial lesion safety and efficacy utilizing a circular pulsed-field ablation catheter including assessment of collateral damage to adjacent tissue in supratherapeutic ablation applications. Hsu, JC., Gibson, D., Banker, R., et al.[2022]

Pulsed field ablation (PFA) for atrial fibrillation (AF) was performed safely in 97 patients, with a high success rate of 100% in isolating pulmonary veins and an 87% freedom from atrial arrhythmias at 180 days follow-up.

The procedure had a median time of 74 minutes and low complication rates, with only 2% experiencing pseudoaneurysm complications, and no serious adverse events like stroke or pulmonary vein stenosis, indicating PFA's potential as an effective alternative to traditional ablation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulsed Field Ablation of Atrial Fibrillation: An Initial Australian Single-Centre Experience. Lee, XW., Freeman, BM., Gunthorpe, NG., et al.[2023]

Pulsed-field ablation (PFA) using a novel system was successfully performed in 10 swine models, achieving complete isolation of pulmonary veins and the superior vena cava with 100% durability of lesions over both subchronic (7 days) and chronic (30 days) periods.

The PFA technique demonstrated a myocardial-specific ablative effect, preserving surrounding tissues such as the phrenic nerve, and showed minimal inflammation and mineralization primarily at the 7-day mark, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time Course of Irreversible Electroporation Lesion Development Through Short- and Long-Term Follow-Up in Pulsed-Field Ablation-Treated Hearts. Grimaldi, M., Di Monaco, A., Gomez, T., et al.[2022]

In a study of 26 patients who underwent repeat procedures after initial treatment with pulsed field ablation (PFA) for atrial fibrillation, only 42% showed complete durable pulmonary vein isolation (PVI), indicating that PFA may not consistently maintain its effectiveness over time.

Reconnection of pulmonary veins was observed in 35% of cases, with gaps primarily located at the anterior aspects of the right-sided pulmonary veins, suggesting specific areas may be more prone to reconnection after PFA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of durability and reconnection patterns at time of repeat ablation after single-shot pulsed field pulmonary vein isolation. Ruwald, MH., Haugdal, M., Worck, R., et al.[2023]

Pulsed field ablation (PFA) for pulmonary vein isolation in atrial fibrillation shows a high single-procedure success rate of 74% for arrhythmia-free survival at a median follow-up of 365 days, indicating its efficacy in treating AF.

The procedure has a favorable safety profile with major complications occurring in only 1.7% of cases, and median procedure times were relatively short at 58 minutes, suggesting PFA is a safe and efficient option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EUropean real-world outcomes with Pulsed field ablatiOn in patients with symptomatic atRIAl fibrillation: lessons from the multi-centre EU-PORIA registry. Schmidt, B., Bordignon, S., Neven, K., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40237369/

Acute Procedural Results of Pulsed Field Cryoablation for ... The evaluation of the chronic 12-month effectiveness of PFCA is ongoing. Keywords: cardiac mapping–3‐dimensional systems; catheter ablation—atrial fibrillation; ...

2. academic.oup.com academic.oup.com/europace/article/26/6/euae134/7689633

State-of-the-art pulsed field ablation for cardiac arrhythmias In the Pulsed AF trial, 45 patients underwent pre-procedural and post-procedural MRI, and SCLs were detected 9% of patients after the ablation.

3. jacc.org jacc.org/doi/10.1016/j.jacep.2022.05.017

Ultra-Low Temperature Cryoablation for Atrial Fibrillation Radiofrequency and cryoballoon ablation reported 1-year freedom from atrial arrhythmias is 70% to 86% in patients with paroxysmal atrial ...

4. dicardiology.com dicardiology.com/content/pulsed-field-cryoablation-eliminated-af-85-after-single-ablation-procedure

Pulsed Field Cryoablation Eliminated AF in 85% After ... At 12 months, freedom from AF after a single procedure was 82%, with 1.5% procedural complications rate when using newer generations of ULTC technology.

5. innovationsincrm.com innovationsincrm.com/latest-news/1918-successful-first-in-human-cases-of-pulsed-field-cryoablation

Adagio Medical Announces Successful First-In-Human ... The patients, a 32-year-old man with paroxysmal AF and a 60-year-old man with persistent AF underwent successful pulmonary vein and posterior wall isolation ...

6. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1111/jce.16680

Acute Procedural Results of Pulsed Field Cryoablation for ... PARALELL is a first-in-human multicenter study evaluating safety and effectiveness of a novel PFCA catheter and system in patients with persistent atrial ...

7. jacc.org jacc.org/doi/10.1016/j.jacasi.2024.09.014

Effectiveness and Safety of Pulsed Field Ablation in ... This meta-analysis illustrates the effectiveness, safety, and procedural outcomes of PFA in AF patients. AF = atrial fibrillation; PFA = pulsed field ablation; ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2772374724003612

Effectiveness and Safety of Pulsed Field Ablation in ... This meta-analysis illustrates the effectiveness, safety, and procedural outcomes of PFA in AF patients. AF = atrial fibrillation; PFA = pulsed field ablation; ...

9. heartrhythmjournal.com heartrhythmjournal.com/article/S1547-5271(24)02372-5/fulltext

Pulsed-field vs cryoballoon vs radiofrequency ablation The purpose of this study was to compare the procedural and long-term outcomes in patients with persistent AF undergoing PVI using PFA, CBA, or RFA.