The PIFPAF-PFA Study

Persistent Atrial Fibrillation Clinical Trial

— PIFPAF-PFA  

Official title:

Pulmonary Vein Isolation With Pulsed-Field Ablation With Versus Without Posterior Wall Ablation in Patients With Symptomatic Persistent Atrial Fibrillation - A Multi-Center Randomized Clinical Trial: The PIFPAF-PFA Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05986526
• Other study ID #: 2023-00885
• Status: Recruiting
• Phase: N/A
• Start date: November 13, 2023
• Est. completion date: July 31, 2028

Study information

• Verified date: June 2024
• Source: Insel Gruppe AG, University Hospital Bern
• Contact: Laurent Roten, MD
• Phone: +41 31 632 52 63
• Email: Laurent.Roten[@]insel.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Pulmonary vein isolation (PVI) is very effective for rhythm control in patients with paroxysmal atrial fibrillation (AF), but less successful in patients with persistent AF. Adding posterior wall ablation (PWA) to PVI is among the most promising ablation strategies to improve arrhythmiafree outcome in patients with persistent AF. Patients with left atrial posterior wall scar may benefit most from adding PWA to PVI. With previous ablation technology, posterior wall isolation (PWI) was difficult to achieve and increased the risk of procedural complications. With pulsed-field ablation (PFA), a technology is now available which is both very effective and safe for complete ablation of the posterior wall. The aim of this trial therefore is to compare the efficacy and procedural safety of two ablation strategies for the treatment of persistent AF using PFA: PVI only versus PVI with added PWA. The endpoint of atrial arrhythmia recurrence within 12 months will be assessed by an implantable cardiac monitor (ICM) with remote monitoring capabilities.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 206
• Est. completion date: July 31, 2028
• Est. primary completion date: July 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Persistent atrial fibrillation documented on a 12 lead ECG, Holter monitor or implantable cardiac device within last 2 years of enrollment

2. Persistent atrial fibrillation is defined as a sustained episode lasting > 7 days

3. Candidate for ablation based on current atrial fibrillation guidelines

4. Continuous anticoagulation with Vitamin-K-Antagonists or a NOAC for =4 weeks prior to the ablation; or a transesophageal echocardiography and/or CT scan that excludes left atrial thrombus =48 hours before the ablation procedure

5. Age of 18 years or older on the date of informed consent

6. Signed informed consent

Exclusion Criteria:

1. Previous left atrial ablation or left atrial surgery

2. Left atrial diameter >60 mm in the parasternal long axis

3. Patients with paroxysmal atrial fibrillation

4. Patients with persistent atrial fibrillation lasting >3 years

5. AF due to reversible causes (e.g. hyperthyroidism, cardiothoracic surgery)

6. Intracardiac thrombus

7. Pre-existing pulmonary vein stenosis or pulmonary vein stent

8. Pre-existing hemidiaphragmatic paralysis

9. Contraindication to anticoagulation or radiocontrast materials

10. Prior mitral valve surgery

11. Severe mitral regurgitation or moderate/severe mitral stenosis

12. Myocardial infarction during the 3-month period preceding the consent date

13. Ongoing triple antithrombotic/anticoagulation therapy

14. Cardiac surgery during the 3-month interval preceding the informed consent date or scheduled cardiac surgery/ transcatheter aortic valve implantation

15. Significant congenital heart defect (including atrial septal defects or pulmonary vein abnormalities but not including a patent foramen ovale)

16. NYHA class III or IV congestive heart failure

17. Left ventricular ejection fraction (LVEF) <35%

18. Hypertrophic cardiomyopathy (wall thickness >1.5 cm)

19. Significant chronic kidney disease (eGFR <30 ml/min)

20. Uncontrolled hyperthyroidism

21. Cerebral ischemic event (stroke or TIA) during the 6-month interval preceding the informed consent date

22. Ongoing systemic infections

23. History of cryoglobulinemia

24. Cardiac amyloidosis

25. Pregnancy (to exclude pregnancy a blood test (HCG) is performed in women < 50 years before inclusion)

26. Life expectancy less than one year per physician opinion

27. Currently participating in any other clinical trial, which may confound the results of this trial

28. Unwilling or unable to comply fully with the study procedures and follow-up

Related Conditions & MeSH terms

• Atrial Fibrillation
• Persistent Atrial Fibrillation

Intervention

Procedure:
• Pulmonary vein isolation without posterior wall ablation
Pulmonary vein isolation with Pulsed field ablation without left atrial posterior wall ablation. At the end of the procedure, an implantable cardiac monitor will be implanted for the purpose of continuous arrhythmia monitoring
• Pulmonary vein isolation with posterior wall ablation
Pulmonary vein isolation with Pulsed field ablation with left atrial posterior wall ablation. At the end of the procedure, an implantable cardiac monitor will be implanted for the purpose of continuous arrhythmia monitoring

Locations

Country	Name	City	State
Switzerland	Cantonal Hospital Baden	Baden
Switzerland	University Hospital Basel	Basel
Switzerland	Inselspital, University Hospital Bern	Bern
Switzerland	University Hospital Lausanne	Lausanne
Switzerland	University Hospital Zürich	Zürich

Sponsors (1)

Lead Sponsor	Collaborator
Insel Gruppe AG, University Hospital Bern

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to first recurrence of any atrial tachyarrhythmia	Time to first recurrence of atrial tachyarrhythmia (atrial fibrillation [AF], atrial flutter [AFL] or atrial tachycardia [AT]) between days 91 and 365 post ablation as detected on an implantable cardiac monitor (ICM). AF, AFL or AT will qualify as a recurrence after ablation if it lasts 120 seconds or longer on the ICM (the minimum programmable episode interval)	Days 91 to 365 post-ablation
Secondary	Incidence of treatment-emergent adverse events: Cardiac tamponade	Number of patients with cardiac tamponade requiring drainage after PVI	Days 0 to 90 post-ablation
Secondary	Incidence of treatment-emergent adverse events: Persistent phrenic nerve palsy	Number of patients with persistent phrenic nerve palsy lasting >24 hours after PVI	Days 0 to 90 post-ablation
Secondary	Incidence of treatment-emergent adverse events: Serious vascular complication	Number of patients with serious vascular complications requiring intervention after PVI	Days 0 to 90 post-ablation
Secondary	Incidence of treatment-emergent adverse events: Stroke or TIA	Number of patients with stroke or TIA after PVI	Days 0 to 90 post-ablation
Secondary	Incidence of treatment-emergent adverse events: Atrioesophageal fistula	Number of patients with atrioesophageal fistula after PVI	Days 0 to 90 post-ablation
Secondary	Incidence of treatment-emergent adverse events: Death	Number of patients with fatal outcome/death after PVI	Days 0 to 90 post-ablation
Secondary	Total procedure time	Procedural endpoint	Day 0, during procedure
Secondary	Total left atrial indwelling time	Procedural endpoint	Day 0, during procedure
Secondary	Total fluoroscopy time	Procedural endpoint	Day 0, during procedure
Secondary	Total radiation dose	Procedural endpoint	Day 0, during procedure
Secondary	Change in hs-Troponin on day 1 post-ablation	Procedural endpoint	Day 1 post-ablation
Secondary	Pre-ablation 3D electro-anatomical mapping: Number of participants with scar as a region that demonstrated reproducibly an area of > 0.5×0.5 cm on the posterior wall with voltage less than 0.5 mV	Procedural endpoint	Day 0, shortly before ablation
Secondary	Post-ablation 3D electro-anatomical mapping: Proportion of isolated veins	Procedural endpoint	Day 0, shortly after ablation
Secondary	Post-ablation 3D electro-anatomical mapping: Proportion of isolated carinas	Procedural endpoint	Day 0, shortly after ablation
Secondary	Post-ablation 3D electro-anatomical mapping: Lesion size	Procedural endpoint	Day 0, shortly after ablation
Secondary	Post-ablation 3D electro-anatomical mapping: Posterior wall ablation success rate	Procedural endpoint	Day 0, shortly after ablation
Secondary	Time to first recurrence of any atrial tachyarrhythmia in patients with versus without left atrial posterior wall scar	Secondary endpoint during follow-up	Day 0 to 36 months post-ablation
Secondary	Time to first recurrence of any atrial tachyarrhythmia in patients with left atrial posterior wall scar and posterior wall ablation versus without posterior wall ablation	Secondary endpoint during follow-up	Day 0 to 36 months post-ablation
Secondary	Percentage of time with cardiac arrhythmia (arrhythmia burden) for each participant between days 0-90 evaluated based on continuous ICM	Secondary endpoint during follow-up	Day 0 to 90 post-ablation
Secondary	Percentage of time with cardiac arrhythmia (arrhythmia burden) for each participant between days 91-365 evaluated based on continuous ICM	Secondary endpoint during follow-up	Day 91 to 365 post-ablation
Secondary	Percentage of time with cardiac arrhythmia (arrhythmia burden) for each participant between days 365 until explantation or end of life (EOL) of the ICM	Secondary endpoint during follow-up	Day 365 post-ablation to explantation of ICM or end of life of ICM (up to 4 years after implantation of ICM)
Secondary	Correlation of AF burden to symptoms and quality of life changes	Secondary endpoint during follow-up; Quality of life wil be measured with the EQ-5D-5L questionnaire where higher scores mean better outcomes; Symptoms will be measured with the AFEQT (Atrial Fibrillation Effect on Quality-of-life) questionnaire where higher scores mean worse outcomes	Day 0 and months 3 and 12 post-ablation
Secondary	Reduction of percentage of time with cardiac arrhythmia (AF burden) by > 90% post ablation procedure	Secondary endpoint during follow-up	Day 0 to 36 months post-ablation
Secondary	Comparison of the prevalence of the type of arrhythmia recurrence during follow-up being AF or organized atrial arrhythmias (AFL or AT)	Secondary endpoint during follow-up	Day 0 to 36 months post-ablation
Secondary	Time to first recurrence of atrial tachyarrhythmia between days 91 and 365 evaluated based on continuous ICM in patients with presence of scar on the PW based on the preablation voltage map versus patients with no scar on the PW	Secondary endpoint during follow-up	Day 91 to 365 post-ablation
Secondary	Number of participants with persistent or paroxysmal AF during follow-up	Secondary endpoint during follow-up	Day 0 to 36 months post-ablation
Secondary	Average heart rate as recorded by the ICM in months 1, 2 and 3 after ablation	Secondary endpoint during follow-up	Months 1, 2 and 3 after ablation
Secondary	Proportion of patients admitted to the hospital or emergency room because of documented recurrence of atrial arrhythmias	Secondary endpoint during follow-up	Day 0 to 36 months post-ablation
Secondary	Proportion of patients undergoing a repeat ablation procedure because of documented recurrence of atrial arrhythmias	Secondary endpoint during follow-up	Day 0 to 36 months post-ablation
Secondary	Number of participants reinitiating of antiarrhythmic drugs during follow-up	Secondary endpoint during follow-up	Day 0 to 36 months post-ablation
Secondary	Number of participants with electrical cardioversion during follow-up	Secondary endpoint during follow-up	Day 0 to 36 months post-ablation
Secondary	Number of reconnected pulmonary veins evaluated during redo procedures	Secondary endpoint during follow-up	During redo procedures between day 1 to 36 months post-ablation
Secondary	Sites of reconnection (anterior, posterior, superior, inferior) of the pulmonary veins evaluated during redo procedures	Secondary endpoint during follow-up	During redo procedures between day 1 to 36 months post-ablation
Secondary	Size of antral scar area (cm²) of the pulmonary veins evaluated during redo procedures	Secondary endpoint during follow-up	During redo procedures between day 1 to 36 months post-ablation
Secondary	Number of reconnected posterior walls evaluated during redo procedures	Secondary endpoint during follow-up	During redo procedures between day 1 to 36 months post-ablation
Secondary	Sites of reconnection of the posterior wall evaluated during redo procedures	Secondary endpoint during follow-up	During redo procedures between day 1 to 36 months post-ablation
Secondary	Size of the scar area (cm²) of the posterior wall evaluated during redo procedures	Secondary endpoint during follow-up	During redo procedures between day 1 to 36 months post-ablation
Secondary	Evolution of Quality of Life after 3 and 12 months	Secondary endpoint during follow-up; Quality of life wil be measured with the EQ-5D-5L questionnaire where higher scores mean better outcomes	Day 0 and months 3 and 12 post-ablation
Secondary	Number of participants with stroke including TIA after 3, 12, 24 and 36 months	Secondary endpoint during follow-up	Months 3, 12, 24 and 36 post-ablation
Secondary	Number of participants with cardiovascular or non-cardiovascular death after 3, 12, 24 and 36 months	Secondary endpoint during follow-up	Months 3, 12, 24 and 36 post-ablation