Renal Denervation + PVI for Atrial Fibrillation

(ERADICATE-AF Trial)

Overseen By Jonathan Steinberg, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Rochester

Disqualifiers: Heart failure, Paroxysmal AF, Renal issues, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Immediate procedure

50 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Renal Denervation + PVI for Atrial Fibrillation?

Research shows that Pulmonary Vein Isolation (PVI) is a key part of treating atrial fibrillation (AF) and is recommended for patients with different types of AF. While the benefit of adding other techniques to PVI is unclear, PVI itself is recognized as a potentially curative treatment for AF. ^{1 2 3 4 5}

Is Renal Denervation + PVI for Atrial Fibrillation safe?

Pulmonary vein isolation (PVI), a key part of the treatment, is generally safe with severe complications occurring in 1-3% of patients. This suggests that while the procedure is mostly safe, there is a small risk of serious complications. ^{1 3 5 6 7}

How is the treatment Renal Denervation + PVI for Atrial Fibrillation different from other treatments?

Renal Denervation + PVI for Atrial Fibrillation is unique because it combines renal denervation, which targets nerves in the kidneys to help control blood pressure, with pulmonary vein isolation (PVI), a procedure that isolates the pulmonary veins to prevent erratic electrical signals in the heart. This combination aims to enhance the effectiveness of treating atrial fibrillation by addressing both heart rhythm and blood pressure issues. ^{1 3 4 8 9}

What is the purpose of this trial?

Pulmonary vein isolation (PVI) is the cornerstone of ablation for atrial fibrillation (AF). Increased cardiac sympathetic stimulation can facilitate AF and reduction can be accomplished by renal artery denervation (RDN). The recently completed randomized trial, ERADICATE-AF, convincingly demonstrated that RDN plus PVI resulted in a reduction in recurrent incident AF for uncontrolled hypertensives. This is a randomized controlled pilot trial, "To Evaluate Renal Artery Denervation in Addition to Catheter Ablation to Eliminate Atrial Fibrillation" (ERADICATE-AF II) to test if RDN plus PVI enhances long-term efficacy vs PVI for persistent AF patients with controlled or without hypertension using implantable loop recordings.

Eligibility Criteria

This trial is for adults over 18 with symptomatic persistent atrial fibrillation, which lasts more than 7 days but less than a year. Participants can either have no history of hypertension or controlled hypertension. They must be eligible for PVI, have renal arteries suitable for denervation, and agree to heart monitoring and follow-up requirements.

Inclusion Criteria

My blood pressure is under control, either naturally or with medication.

I am older than 18 years.

I have had atrial fibrillation symptoms for more than 7 days but less than a year.

Exclusion Criteria

I've had a procedure on my kidney arteries that prevents me from getting ablation treatment.

I have had atrial fibrillation that comes and goes or has lasted for more than a year.

I have had a procedure to correct an irregular heartbeat.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo pulmonary vein isolation (PVI) and may receive additional renal artery denervation (RDN)

Immediate procedure

1 visit (in-person)

Follow-up

Participants are monitored for safety, AF burden, and other clinical outcomes

12 months

Regular visits (in-person and virtual) at 0, 1, 3, 6, and 12 months

Long-term Follow-up

Participants are monitored for long-term outcomes such as AF recurrence and quality of life

Beyond 12 months

Treatment Details

Interventions

• Catheter Ablation
• Renal Artery Denervation

Trial Overview The study is testing if adding renal artery denervation (RDN) to the standard catheter ablation treatment called pulmonary vein isolation (PVI) improves outcomes in patients with persistent atrial fibrillation. It's a randomized pilot trial where some participants will receive both treatments while others only PVI.

Participant Groups

Group I: Pulmonary vein isolation + renal artery denervation Experimental Treatment 2 Interventions

After completion of the standard PVI, radiofrequency ablation of bilateral renal arteries

Group II: Pulmonary vein isolation Active Control 1 Intervention

Electrical isolation by cryoballoon of all pulmonary veins

Catheter Ablation is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Pulmonary Vein Isolation (PVI) for:

• Symptomatic paroxysmal or persistent atrial fibrillation
• Heart failure with reduced left ventricular fraction

Approved in United States as Pulmonary Vein Isolation (PVI) for:

• Symptomatic paroxysmal or persistent atrial fibrillation
• Heart failure with reduced left ventricular fraction

Approved in Canada as Pulmonary Vein Isolation (PVI) for:

• Symptomatic paroxysmal or persistent atrial fibrillation
• Heart failure with reduced left ventricular fraction

Who Is Running the Clinical Trial?

University of Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

Patients with atrial fibrillation (AF) who underwent pulmonary vein isolation plus additional atrial ablations (PVI+) had a significantly higher rate of maintaining normal sinus rhythm in the first year compared to those who only had PVI, with a relative risk of 1.10 based on 21 randomized controlled trials and 3 non-randomized trials.

The most notable improvement was seen with PVI+ left atrial linear ablations, which showed a relative risk of 1.16, indicating that this specific approach may enhance the effectiveness of AF treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of catheter ablation strategies for rhythm control in patients with atrial fibrillation: a meta-analysis. Assasi, N., Xie, F., Blackhouse, G., et al.[2021]

A meta-analysis of 8 studies showed that adding complex fractionated atrial electrogram (CFAE) ablation to pulmonary vein isolation (PVI) significantly improves freedom from atrial tachyarrhythmia (AT) in patients with nonparoxysmal atrial fibrillation (AF), with a relative risk of 1.32.

In contrast, for patients with paroxysmal AF, the addition of CFAE ablation did not provide any significant benefit over PVI alone, indicating that this combined approach may be more effective for nonparoxysmal cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary vein isolation with complex fractionated atrial electrogram ablation for paroxysmal and nonparoxysmal atrial fibrillation: A meta-analysis. Hayward, RM., Upadhyay, GA., Mela, T., et al.[2021]

The novel irrigated multielectrode ablation catheter successfully isolated 100% of targeted pulmonary veins in 25 patients with paroxysmal atrial fibrillation, demonstrating high acute efficacy with a mean procedure time of 110 minutes and no complications.

The procedure was safe, with no cases of acute pulmonary vein stenosis detected, and showed improved efficiency over time, with reduced procedure and fluoroscopy times after a short learning curve.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial results of using a novel irrigated multielectrode mapping and ablation catheter for pulmonary vein isolation. Shin, DI., Kirmanoglou, K., Eickholt, C., et al.[2016]

In a study of 486 patients with persistent and long-standing persistent atrial fibrillation (AF) treated with cryoballoon ablation, the procedure demonstrated a high acute success rate of 97.6% for pulmonary vein isolation (PVI).

The procedure was found to be safe, with a low complication rate of 4.3%, and showed reasonable mid-term success rates for freedom from AF, with 63.9% of patients remaining event-free at 12 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary vein isolation cryoablation for patients with persistent and long-standing persistent atrial fibrillation: Clinical outcomes from the real-world multicenter observational project. Tondo, C., Iacopino, S., Pieragnoli, P., et al.[2018]

The STOP Persistent AF trial showed that cryoballoon ablation is a safe and effective treatment for patients with drug-refractory persistent atrial fibrillation, achieving a 54.8% success rate in maintaining freedom from AF, AFL, or AT at 12 months.

With only one primary safety event reported (0.6% rate), the procedure demonstrated a favorable safety profile, alongside significant improvements in quality of life as measured by the AFEQT and SF-12 questionnaires.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cryoballoon ablation of pulmonary veins for persistent atrial fibrillation: Results from the multicenter STOP Persistent AF trial. Su, WW., Reddy, VY., Bhasin, K., et al.[2021]

In a study of 58 patients undergoing pulmonary vein isolation (PVI) for atrial fibrillation, using a circular mapping catheter (CMC) inside the pulmonary vein during laser ablation was found to be feasible and safe, with no major complications reported in this group.

The mapping-guided approach led to a significant reduction in unsuccessfully isolated pulmonary veins after a learning curve, but both mapping-guided and standard techniques showed similar rates of atrial fibrillation-free survival after 16.7 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new circular mapping-guided approach for endoscopic laser balloon pulmonary vein isolation. Gal, P., Smit, JJJ., Adiyaman, A., et al.[2020]

In a study of 13,823 patients undergoing pulmonary vein isolation (PVI) for atrial fibrillation, the overall complication rate was low at 3.6%, but patients treated with conventional radiofrequency (C-RF) had higher rates of cardiac tamponades and vascular complications compared to other methods.

Female patients were found to be at a higher risk for complications, with nearly three times the odds of experiencing cardiac tamponade and double the odds of bleeding complications compared to male patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications in pulmonary vein isolation in the Netherlands Heart Registration differ with sex and ablation technique. Mol, D., Houterman, S., Balt, JC., et al.[2021]

In a study of 161 patients with atrial fibrillation, pulmonary vein isolation (PVI) using a multi-electrode radiofrequency ablation (PVAC) showed a comparable success rate to conventional point-by-point RF ablation (CPVI) after 3 years, with success rates of 65% and 55% respectively.

Most recurrences of atrial fibrillation occurred within the first year after the procedure for both PVAC and CPVI, indicating that early monitoring is crucial for managing potential relapses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duty-cycled multi-electrode radiofrequency vs. conventional irrigated point-by-point radiofrequency ablation for recurrent atrial fibrillation: comparative 3-year data. De Greef, Y., Buysschaert, I., Schwagten, B., et al.[2022]

Recent innovations in catheter-based ablation for atrial fibrillation, such as advanced radiofrequency catheters and single-shot balloon catheters, have improved the efficiency and effectiveness of pulmonary vein isolation procedures.

New technologies like pulsed field ablation (PFA) and esophageal protection devices are being developed to enhance safety by minimizing collateral damage and reducing complications, indicating a promising future for atrial fibrillation treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovations in atrial fibrillation ablation. Kim, JA., Khan, K., Kherallah, R., et al.[2023]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of catheter ablation strategies for rhythm control in patients with atrial fibrillation: a meta-analysis. [2021]

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

Pulmonary vein isolation with complex fractionated atrial electrogram ablation for paroxysmal and nonparoxysmal atrial fibrillation: A meta-analysis. [2021]

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

Initial results of using a novel irrigated multielectrode mapping and ablation catheter for pulmonary vein isolation. [2016]

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

Pulmonary vein isolation cryoablation for patients with persistent and long-standing persistent atrial fibrillation: Clinical outcomes from the real-world multicenter observational project. [2018]

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

Cryoballoon ablation of pulmonary veins for persistent atrial fibrillation: Results from the multicenter STOP Persistent AF trial. [2021]

6. Ireland pubmed.ncbi.nlm.nih.gov

A new circular mapping-guided approach for endoscopic laser balloon pulmonary vein isolation. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Complications in pulmonary vein isolation in the Netherlands Heart Registration differ with sex and ablation technique. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Duty-cycled multi-electrode radiofrequency vs. conventional irrigated point-by-point radiofrequency ablation for recurrent atrial fibrillation: comparative 3-year data. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Innovations in atrial fibrillation ablation. [2023]