Pulsed Field Ablation for Atrial Fibrillation

(PARALELL Trial)

Recruiting in Palo Alto (17 mi)

+5 other locations

Overseen by Atul Verma, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Adagio Medical

Disqualifiers: Structural heart disease, BMI > 40, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

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 data supports the effectiveness of the treatment Pulsed Field Ablation for Atrial Fibrillation?

Research shows that Pulsed Field Ablation (PFA) is a promising new treatment for atrial fibrillation, potentially reducing complications and improving effectiveness compared to traditional methods. Studies indicate that PFA is safe and effective for isolating pulmonary veins, which is crucial in treating atrial fibrillation. ^{1 2 3 4 5}

Is pulsed field ablation (PFA) safe for humans?

Pulsed field ablation (PFA) has shown favorable safety data in studies, with potential safety advantages over other methods like radiofrequency and cryoablation. Research indicates it is generally safe for treating atrial fibrillation, with a unique safety profile and minimal collateral damage to surrounding tissues. ^{2 5 6 7 8}

How is the Pulsed Field Ablation treatment for atrial fibrillation different from other treatments?

Pulsed Field Ablation (PFA) is unique because it uses a nonthermal, tissue-selective approach to treat atrial fibrillation, potentially reducing complications and improving effectiveness compared to traditional thermal ablation methods. It employs a multichannel irreversible electroporation generator and catheter system, which may offer more durable results and fewer side effects. ^{1 2 3 9 10}

Research Team

Atul Verma, MD

Principal Investigator

McGill University Health Centre; Montreal, Canada

Eligibility Criteria

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 between 18 and 80 years old.

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.

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.

Trial Timeline

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

Treatment Details

Interventions

• Adagio PFA and PFCA Systems (Atrial Ablation)

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.

Participant Groups

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

Who Is Running the Clinical Trial?

Adagio Medical

Lead Sponsor

Trials

8

Recruited

930+

Findings from Research

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]

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]

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]

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]

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 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]

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]

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]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Pulsed Field Ablation of Atrial Fibrillation: An Initial Australian Single-Centre Experience. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pulmonary vein isolation with pulsed field ablation vs. novel cryoballoon ablation system for atrial fibrillation. [2023]

3. United States 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. [2022]

4. England 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. [2023]

5. England 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. [2023]

6. Netherlands 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. [2023]

7. United States 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. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Clinical Outcomes by Sex After Pulsed Field Ablation of Atrial Fibrillation. [2023]

9. United States 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. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Characterization of durability and reconnection patterns at time of repeat ablation after single-shot pulsed field pulmonary vein isolation. [2023]