The COMBINE-AF Trial

NCT07633509 | Not Yet Recruiting DMC FDA Device

• 1 other identifier: The COMBINE-AF Trial
• Study Type: interventional
• Target: 430
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this clinical trial is to test if a more complete ablation procedure works better than the standard procedure for people with long-lasting atrial fibrillation (AF). AF is a heart rhythm problem that can cause a fast or uneven heartbeat. This study will include 430 people with long-lasting AF that has lasted 1 to 3 years. Participants will be put into one of two groups by chance: First group (control): They will receive pulsed-field ablation (PFA), a type of energy that can stop the faulty heart signals. They will have isolation of the pulmonary veins and the back wall of the left atrium. Second group (study): They will receive the same PFA procedure plus extra ablation lines (modified linear ablation) using radiofrequency energy. This includes ablation of the mitral isthmus (with ethanol infusion into a small vein called the vein of Marshall) and the cavotricuspid isthmus. Participants will be followed for 12 months after the procedure with clinic visits, electrocardiograms (ECGs), and heart rhythm monitors. The main outcome is whether participants stay in normal heart rhythm (sinus rhythm) without any AF episodes lasting more than 30 seconds at 12 months. Researchers will also look at procedure time, complication rates, quality of life, and other rhythm outcomes. This study will help show if the more complete ablation procedure leads to better long-term results for people with long-lasting AF.

Conditions

Atrial Fibrillation (AF); Atrial Fibrillation Catheter Ablation

Keywords

Atrial Fibrillation; Catheter Ablation; Long-standing Persistent Atrial Fibrillation; Pulsed Field Ablation; Radiofrequency Ablation

Outcome Measures

Primary Outcomes (1)

• Freedom from Atrial Arrhythmia Recurrence at 12 Months

  The primary outcome is the proportion of participants remaining in normal sinus rhythm at 12 months after the ablation procedure, after excluding a 3-month blanking period immediately following the procedure. Treatment success is defined as freedom from any documented episode of atrial fibrillation, atrial flutter, or atrial tachycardia lasting more than 30 seconds, as recorded by electrocardiogram (ECG) or Holter monitoring between 3 months and 12 months post-ablation.

  Between 3 months and 12 months following the ablation procedure, excluding the initial 3-month blanking period

Secondary Outcomes (7)

• Atrial Fibrillation Burden at 12 Months

  From month 3 to month 12 after the ablation procedure

• Incidence of Serious Procedure-Related Complications

  From the start of the ablation procedure to 30 days post-procedure

• Cardiovascular Hospitalization During Follow-up

  From the date of ablation to 12 months post-ablation

• Total Procedure Time

  On the day of the ablation procedure

• Acute Success Rates of Linear Ablation Lesions

  During the ablation procedure (intraoperative)

Study Arms (2)

Pulmonary Vein Isolation + Posterior Wall Isolation (PFA Only)

ACTIVE COMPARATOR

Participants in this arm receive pulsed-field ablation (PFA) to isolate all four pulmonary veins and to create a box lesion isolating the left atrial posterior wall. No additional linear ablation lines are performed. The procedure endpoint is confirmed bidirectional block of all targeted veins and the posterior wall. CTI ablation will be performed only if typical atrial flutter is documented.

Device: Pulsed Field Ablation Catheter

PVI + Posterior Wall + Modified Linear Ablation (PFA + RF)

EXPERIMENTAL

Participants in this arm receive the same PFA-based pulmonary vein isolation and posterior wall box isolation as the control arm. In addition, they undergo modified linear ablation using radiofrequency (RF) energy. This includes: Mitral isthmus line supplemented by ethanol infusion into the vein of Marshall. Cavotricuspid isthmus line. The goal is to achieve bidirectional block across all ablation lines.

Device: Pulsed Field Ablation Catheter; Drug: Ethanol; Device: Radiofrequency Ablation Catheter

Interventions

Pulsed Field Ablation Catheter DEVICE

Use of a pentaspline pulsed field ablation (PFA) catheter to perform circumferential pulmonary vein isolation (PVI) and left atrial posterior wall box isolation. The endpoint is confirmed bidirectional block of all targeted veins and the posterior wall.

PVI + Posterior Wall + Modified Linear Ablation (PFA + RF); Pulmonary Vein Isolation + Posterior Wall Isolation (PFA Only)

Ethanol DRUG

Infusion of absolute ethanol into the vein of Marshall (VOM) under balloon occlusion to facilitate mitral isthmus linear ablation.

PVI + Posterior Wall + Modified Linear Ablation (PFA + RF)

Radiofrequency Ablation Catheter DEVICE

Use of a contact-force sensing radiofrequency (RF) ablation catheter to create modified linear lesions: mitral isthmus line (combined with ethanol infusion) and cavotricuspid isthmus line. The goal is bidirectional block across all linear lesions.

PVI + Posterior Wall + Modified Linear Ablation (PFA + RF)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Symptomatic patients with long-standing persistent atrial fibrillation.
• Duration of atrial fibrillation between 1 and 3 years.
• Age 18 to 75 years.
• Left atrial diameter between 43 mm and 55 mm.
• Documentation of atrial fibrillation within 3 years prior to enrollment.
• Willing and able to comply with the study protocol and provide written informed consent.

You may not qualify if:

• Paroxysmal atrial fibrillation, or evidence of sinus rhythm on electrocardiogram within the past year.
• Persistent atrial fibrillation lasting less than 1 year or more than 3 years.
• Left atrial thrombus.
• Prior catheter ablation for atrial fibrillation.
• Coexisting severe organic heart disease (e.g., severe valvular heart disease, hypertrophic cardiomyopathy, dilated cardiomyopathy, etc.).
• Left atrial diameter (LAD) \>55 mm.
• Left ventricular ejection fraction (LVEF) \<40%.
• Known allergy or contraindication to low-molecular-weight heparin, warfarin, or direct oral anticoagulants.
• Undergoing a "one-stop" procedure combining atrial fibrillation ablation with left atrial appendage closure.
• Allergy to alcohol or contrast media.
• Pulmonary artery systolic pressure \>50 mmHg.
• Unstable angina pectoris.
• Percutaneous coronary intervention (PCI) within the past 3 months.
• Cardiac surgery within the past 6 months.
• Planned heart transplantation.

Sponsors & Collaborators

• Yunlong Wang: lead
• Beijing Huahsia Foundation: collaborator
• Boston Scientific Corporation: collaborator

Study Sites (3)

Fuwai Hospital

Beijing, Beijing Municipality, 100039, China

Location

Beijing Anzhen Hospital, Capital Medical University

Beijing, Beijing Municipality, 101118, China

Location

Jiangsu Province Hospital (The First Affiliated Hospital with Nanjing Medical University , Jiangsu Women and Children Health Hospital）

Nanjing, Jiangsu, 210029, China

Location

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Ethanol; Catheter Ablation

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Alcohols; Organic Chemicals; Radiofrequency Ablation; Radiofrequency Therapy; Therapeutics; Ablation Techniques; Surgical Procedures, Operative

Central Study Contacts

Yunlong Wang, PhD

CONTACT

+86 10 81992202; yunlong76818@126.com

Yijie Liu, PhD

CONTACT

yj-sage@qq.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: This is a single-blind study. Participants are blinded to their assigned treatment group (control vs. study). Procedure operators are not blinded due to the nature of the interventions. All other study personnel involved in outcome assessment (e.g., ECG core laboratory, Holter analysis) and statistical analysis are blinded to group assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, Department of Cardiology

Model Details: Participants will be randomly assigned in a 1:1 ratio to one of two parallel groups. The control group receives pulsed-field ablation (PFA) for pulmonary vein isolation and posterior wall isolation. The study group receives the same PFA procedure plus additional modified linear ablation using radiofrequency energy (mitral isthmus line supplemented by ethanol infusion into the vein of Marshall, and cavotricuspid isthmus line). No cross-over between groups is planned.

Study Record Dates

• First Submitted: June 2, 2026
• First Posted: June 8, 2026
• Study Start: June 15, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: June 8, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)