Renal Denervation for Atrial Fibrillation

Recruiting at 7 trial locations

Overseen By Betsy Ellsworth, MSN ANP

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Vivek Reddy

Must be taking: Antihypertensives

Disqualifiers: Long-standing AF, NYHA class IV, others

Stay on Your Current Meds You can continue your current medications while participating

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: Unknown

Duration: Expected to take 6 months to set up clinical sites and 9 months for accrual

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether an additional procedure, called renal denervation, can help prevent atrial fibrillation (AF) from recurring in individuals with high blood pressure who are undergoing a second AF ablation (also known as catheter ablation). Participants are divided into two groups: one receives only the standard AF ablation, while the other receives both AF ablation and renal denervation. Suitable candidates for this trial have experienced a return of AF after a previous ablation and have high blood pressure, possibly requiring medication. As an unphased trial, this study provides an opportunity to explore innovative treatment options that might improve the condition.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the trial involves patients with hypertension who are already on antihypertensive medication, it seems likely that you may continue your current medications.

What prior data suggests that renal denervation is safe for atrial fibrillation patients?

Research shows that renal denervation (RDN) is generally safe for people with atrial fibrillation (AF) and high blood pressure. Studies have found a complication rate of about 6.32% for RDN, indicating that while some side effects might occur, they are uncommon.

In earlier studies, combining RDN with pulmonary vein isolation (PVI) improved outcomes for people with AF and high blood pressure. This combination did not increase complications compared to PVI alone, suggesting that adding RDN is well-tolerated by patients.

Overall, past research supports RDN as a safe treatment option for people with AF and high blood pressure. However, like any medical procedure, it carries risks, and discussing these with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatment for atrial fibrillation, which typically involves catheter ablation alone, this innovative approach combines catheter ablation with renal denervation. Researchers are excited about this combination because renal denervation targets the nerves around the kidneys that contribute to high blood pressure and irregular heart rhythms, potentially offering a more comprehensive solution. This dual approach aims to not only treat the symptoms but also address the underlying neural pathways that may cause atrial fibrillation, making it a promising option for patients who haven't responded well to traditional therapies.

What evidence suggests that renal denervation could be effective for preventing atrial fibrillation recurrence?

In this trial, participants will be assigned to one of two treatment arms. Research has shown that adding renal denervation to catheter ablation, one of the treatment arms, can reduce the chances of atrial fibrillation (AF) returning in people with high blood pressure. One study found that combining these treatments lowered the risk of AF recurrence by 32% compared to using ablation alone, the other treatment arm. Another study suggested that renal denervation can reduce heart activity, potentially preventing AF. Overall, these findings indicate that including renal denervation in the treatment plan might improve outcomes for those with AF and high blood pressure. ^{1 2 3 4 6}

Who Is on the Research Team?

Vivek Reddy, MD

Principal Investigator

MOUNT SINAI HOSPITAL

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a history of hypertension and atrial fibrillation, who have had a successful AF ablation before and are scheduled for another. They must be willing to follow the study's rules and attend all follow-ups. People can't join if they've had an AF ablation recently, severe heart failure, certain kidney issues or artery problems, drug/alcohol dependency, other device treatments for hypertension, or inflammatory bowel disease.

Inclusion Criteria

I have high blood pressure or am on medication for it.

Willingness to adhere to study restrictions and comply with all post-procedural follow-up requirements

I am scheduled for another AF ablation after a successful first procedure.

Exclusion Criteria

You have used other devices for treating high blood pressure before, such as the ROX Coupler, Mobius stent, or the CVRx barostimulator device.

The main blood vessel in the kidney is less than 20 millimeters long and can be treated.

You are not expected to live for more than 1 year due to a medical condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo either catheter ablation alone or catheter ablation with renal sympathetic denervation

Expected to take 6 months to set up clinical sites and 9 months for accrual

Follow-up

Participants are monitored for safety and effectiveness after treatment, including freedom from atrial arrhythmias and quality of life assessments

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Catheter Ablation
• Renal Denervation

Trial Overview

The ULTRA-HFIB-Redo trial is testing whether adding renal sympathetic denervation to the usual catheter ablation treatment helps prevent atrial fibrillation from coming back in patients with high blood pressure. Participants will either receive just the catheter ablation (control) or both procedures (intervention), assigned randomly at a ratio of two intervention participants to one control.

How Is the Trial Designed?

Group I: Catheter ablation + renal denervation Experimental Treatment 2 Interventions

Catheter ablation + renal denervation

Group II: Catheter ablation only Active Control 1 Intervention

Catheter ablation

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?

Vivek Reddy

Lead Sponsor

Trials

23

Recruited

5,700+

Published Research Related to This Trial

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 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 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]

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]

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 67 patients with atrial fibrillation (AF) treated with the PV ablation catheter (PVAC), 48.7% of patients with paroxysmal AF achieved sustained sinus rhythm without anti-arrhythmic drugs after a single procedure, indicating good efficacy for this group.

The procedure was found to be safe, but only 13.3% of patients with persistent AF achieved sustained sinus rhythm without medication, suggesting that PVAC may not be as effective for this type of AF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of multi-electrode duty-cycled radiofrequency ablation in patients with paroxysmal and persistent atrial fibrillation. Koźluk, E., Balsam, P., Peller, M., et al.[2022]

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]

Citations

1.

nature.com

nature.com/articles/s41371-022-00658-0

Renal denervation for atrial fibrillation

The study aims to compare clinical outcomes following renal denervation (RDN) in hypertensive patients with atrial fibrillation (AF).

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10697905/

Long-term safety and efficacy of renal sympathetic ...

In patients with hypertension and symptomatic AF, stand-alone RDN reduced BP but did not significantly reduce AF burden up until 3 years of follow-up.

3.

jacc.org

jacc.org/doi/10.1016/j.jacep.2020.08.013

Renal Sympathetic Denervation as Upstream Therapy ...

When combined in a meta-analysis including 6 studies (n = 725), adjunctive RSDN significantly decreased the risk of AF recurrence (risk ratio [RR]: 0.68; 95% ...

4.

jamanetwork.com

jamanetwork.com/journals/jama/fullarticle/2759005

Effect of Renal Denervation and Catheter Ablation vs ...

Importance Renal denervation can reduce cardiac sympathetic activity that may result in an antiarrhythmic effect on atrial fibrillation.

5.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1547527122021609

Renal denervation prevents subclinical atrial fibrillation in ...

Catheter-based renal denervation (RD), in addition to pulmonary vein isolation (PVI), reduces atrial fibrillation (AF) recurrence in hypertensive patients.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11340072/

Efficacy of renal denervation as an adjunct to pulmonary ...

Adding RDN to PVI in patients with AF and resistant HTN was associated with a reduction of blood pressure levels and AF recurrence.