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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding renal artery denervation (RDN) to the usual treatment of pulmonary vein isolation (PVI) reduces atrial fibrillation (AF) in people with persistent symptoms. AF is a heart condition that causes irregular and often rapid heartbeats. The trial compares two groups: one receiving only PVI (catheter ablation for atrial fibrillation) and another receiving both PVI and RDN. Individuals with AF lasting more than a week but less than a year, who can undergo PVI, and have either no high blood pressure or controlled high blood pressure, might be suitable candidates. As an unphased trial, this study provides a unique opportunity to explore innovative treatment combinations for AF.

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 prior data suggests that this method is safe for atrial fibrillation patients?

In a previous study, patients who underwent pulmonary vein isolation (PVI) experienced major complications at a low rate, with only about 1.9% facing significant issues. This suggests that PVI is generally safe. Another study found immediate safety concerns in PVI occurred in just 2.6% of cases, which is quite low.

Research has also shown that renal artery denervation (RDN) is safe. One study reported no major problems in patients 30 days or even 6 months after the procedure. Another study found no cases of serious artery narrowing or the need for additional treatment in RDN patients over two years.

Both PVI and RDN have demonstrated strong safety records in studies, indicating they are well-tolerated by most patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about combining pulmonary vein isolation (PVI) with renal artery denervation for atrial fibrillation because it targets the condition in a novel way. While traditional treatments like catheter ablation focus solely on isolating the pulmonary veins, this approach adds renal artery denervation, which could help in reducing sympathetic nerve activity that may contribute to the condition. By addressing multiple pathways, this combined method has the potential to improve outcomes more effectively than PVI alone.

What evidence suggests that this trial's treatments could be effective for atrial fibrillation?

Research shows that isolating the pulmonary veins (PVI) is an important way to treat atrial fibrillation (AF), a common heart rhythm problem. In one study, 82% of patients did not experience a return of AF after one year. However, over time, the success rate decreases, with about 56% of patients still benefiting after nearly four years.

In this trial, one group of participants will receive PVI alone, while another group will receive a combination of PVI and renal artery denervation (RDN). Adding RDN to PVI might improve these results. Studies have found that RDN can lower blood pressure and reduce the return of AF, especially in people with high blood pressure that is hard to control. Specifically, the ERADICATE-AF trial showed that combining RDN with PVI lowered the chances of AF coming back in patients with uncontrolled high blood pressure. This suggests that using both RDN and PVI together might provide better long-term results for people with persistent AF. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

Citations

1. heartrhythmjournal.com heartrhythmjournal.com/article/S1547-5271(25)02379-3/fulltext

One-year outcomes of a conformable single-shot pulsed ... PVI durability with PULSE3 (n = 40) was 98% (per-vein) and 93% (per-patient). One-year freedom from AA recurrence was 82.0% (95% CI:73.0%–88.3%) ...

2. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2800186

Effect of Catheter Ablation Using Pulmonary Vein Isolation ... Among patients with persistent AF undergoing first-time catheter ablation, the addition of PWI to PVI did not improve freedom from atrial arrhythmias compared ...

3. ahajournals.org ahajournals.org/doi/10.1161/JAHA.123.029651

Long‐Term Impact of Additional Ablation After Pulmonary ... Left atrial linear ablation in addition to pulmonary vein isolation may improve rhythm outcomes in patients with persistent atrial fibrillation.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5633714/

The Short and Long-Term Efficacy of Pulmonary Vein Isolation ... Following a single procedure, at 48.8-months follow-up a 56% and 57% success rate could be achieved, while after repeat ablation (second ablation: 18 pts in ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2892619/

Five-Year Outcomes after Segmental Pulmonary Vein ... Overall five-year outcomes after PVI for PAF are consistent with previously reported shorter term follow-up (≤2 years); however, late recurrences (>2 years) ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38614191/

Pulsed-field vs cryoballoon vs radiofrequency ablation Acute safety events occurred in 2.3%, 2.6%, and 0.8% in the PFA, CBA, and RFA groups, respectively (P = .545). The 1-year confounder-adjusted ...

7. heartrhythmjournal.com heartrhythmjournal.com/article/S1547-5271(25)00125-0/fulltext

Safety and efficacy of catheter ablation for atrial fibrillation ... The primary safety outcomes were observed in 3 patients. One patient experienced prolonged superficial bleeding from the wound edges (femoral ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30593868/

Safety and outcomes of catheter ablation for atrial ... When performed at experienced centers, AF ablation is safe and effective even among patients with the most complex forms of CHD.

9. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.123.064959

Safety and Effectiveness of Pulsed Field Ablation to Treat ... The registry also demonstrated a low rate of major complications at 1.9% with no instances of esophageal injury or pulmonary vein stenosis. What Are the ...