Clinical trial NCT05119231: Pulmonary Vein Isolation vs SHAM-pulmonary Vein Isolation for Symptomatic Relief in Patients With AF
Official title: Pulmonary Vein Isolation Versus SHAM-pulmonary Vein Isolation for Symptomatic Relief in Patients With Atrial Fibrillation- a Randomised Trial - PVI-SHAM-AF
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Atrial Fibrillation
Keywords: Arrhythmias, Cardiac
Heart Disease
ECG Monitoring
Lead sponsor: University of Leipzig
Sponsor class: OTHER
First posted: 2021-11-15
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized, parallel group, sham-controlled and double-blinded multicenter trial
Primary purpose: TREATMENT

Brief summary: Being the most common arrhythmia, atrial fibrillation (AF) is a high burden of public health with an increasing prevalence in our aging population. Interventional treatment of atrial fibrillation by catheter ablation is one of the treatment pillars in the complex field of "better symptom control" based on current Guidelines. Catheter ablation of atrial fibrillation is based on electrical isolation of the pulmonary veins (pulmonary vein isolation: PVI) from the left atrium. The main benefit and goal of PVI in AF patients is the reduction of AF-related symptoms, resulting in an improvement of quality of life. It was shown, that catheter ablation failed to prove a difference in AF recurrence after PVI compared to medical therapy in the first 18 month of follow-up. It was also shown, that these episodes will become more asymptomatic. This raises concerns that the symptomatic improvement might be the result of a placebo effect, which will be elucidated with this study.

Detailed description: Being the most common arrhythmia, atrial fibrillation (AF) is a high burden of public health with an increasing prevalence in our aging population. Interventional treatment of atrial fibrillation by catheter ablation is one of the treatment pillars in the complex field of "better symptom control" based on current Guidelines. Atrial fibrillation is commonly induced and maintained by abnormal electrical impulses originating in the pulmonary veins. Catheter ablation of atrial fibrillation is based on electrical isolation of the pulmonary veins (pulmonary vein isolation: PVI) from the left atrium. This is achieved either by heating (Radiofrequency ablation) or freezing (Cryoablation) of the tissues. By inducing the formation of scar tissue, the pulmonary veins are "electrically isolated" and abnormal electrical signals are not transferred any more to the left atrium.

The main benefit and goal of PVI in AF patients is the reduction of AF-related symptoms, resulting in an improvement of quality of life. The effect was shown to be significantly higher compared with conventional medical treatment. In contrast, there is no evidence for a substantial effect of PVI on hard clinical endpoints. The recent large randomized controlled trial CABANA (Catheter ABlation vs. ANtiarrhythmic Drug Therapy for Atrial Fibrillation) did not show a reduction of the primary composite endpoint of death, disabling stroke, serious bleeding and cardiac arrest in the intention-to-treat analysis although the results are highly controversial due to the high crossover rate.

Up to now, the only patient population with evidence for a prognostic benefit of PVI in symptomatic AF are patients with a heart failure and a reduced ejection fraction (HFrEF). In the CASTLE-AF trial, a relative risk reduction for all-cause mortality of 47% was shown for HFrEF patients with AF ablation compared with conventional treatment.

7-Day Holter monitoring in patients 6 month after treatment with PVI revealed a significant increase in asymptomatic AF episodes. Furthermore, the MANTRA-PAF randomised trial (Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation) failed to prove a difference in AF recurrence after PVI compared to medical therapy in the first 18 month of follow-up.

This raises concerns that the symptomatic improvement might be the result of a placebo effect.

PVI-SHAM-AF is a prospective, double-blinded, sham-controlled, randomized, multicenter trial whose aim is to compare the effect of catheter-based ablation on patient reported outcomes based on common AF questionnaires with a sham procedure. 260 patients without previous PVI or surgical treatment of atrial fibrillation, a LVEF \>35% and an indication for interventional treatment of AF with pulmonary vein isolation based on current Guidelines (ESC 2020) will be enrolled and randomized 2:1 to undergo either PVI or sham procedure. The latter will include deep sedation as performed during standard PVI treatment for at least one hour, introduction of femoral sheaths and if necessary electrical cardioversion in patients with persisting AF. No catheter will be placed within the participant. The official procedure protocol will include no details about the intervention; postinterventional care will be conducted independent of whether a catheter ablation or sham procedure was performed, based on the respective PVI protocol.

Patient will be followed up for one year with visit at 3, 6 and 12 months. Each of these visits include questionnaires for AF related Symptoms (AFEQT, SF-36 and EQ-5D); 7-Day Holter Monitoring will be performed 6 months after the procedure. Participants will be unblinded after 12 months. The primary endpoint will be the difference of AFEQT sum scores evaluated at 6 months to baseline.

Eligibility criteria: Inclusion Criteria:

1. Patients with symptomatic atrial fibrillation scheduled for pulmonary vein isolation
2. Class I or class IIa indication for pulmonary vein isolation by current guidelines
3. Age ≥ 18 years
4. Written informed consent

Exclusion Criteria:

1. History of previous pulmonary vein isolation or surgical treatment of atrial fibrillation
2. Reversible causes of atrial fibrillation (e. g. thyroid disorder, acute alcohol intoxication, recent major surgical procedures, trauma or acute infection)
3. Moderate or severe valvular heart disease
4. CHA2DS2-VASc-Score =0 (males) or 1 (females) or contraindication to oral anticoagulation
5. Acute coronary syndrome, percutaneous coronary intervention, valve surgery or percutaneous intervention or cardiac bypass surgery and stroke within the last 3 months
6. Reduced left ventricular ejection fraction \< 35%
7. Hypertrophic obstructive cardiomyopathy
8. Medical conditions limiting the expected survival to \< 1 year
9. Participation in any other randomized controlled trial
10. Women of childbearing potential without appropriate contraceptive measures (oral contraceptives, vaginal ring, intrauterine devices, implanon, injections, partner with vasectomy) pregnant woman or woman with desire for children
11. Any condition that - in the opinion of the investigator - may prevent the subject from adhering to the study protocol (e.g. history of non-compliance, drug addiction)
12. Subjects under legal supervision or guardianship
13. Unable to give informed consent

Primary outcomes:
measure: difference of AFEQT sum scores evaluated at 6 months
timeFrame: 6 months after randomisation compared to baseline
Secondary outcomes:
measure: the longitudinal change of the AFEQT score
timeFrame: baseline - 3, 6 and 12 months
measure: difference of EQ-5D scores
timeFrame: at 6 months to baseline
measure: difference of SF-36 scales
timeFrame: at 6 months to baseline
measure: the change of EQ-5D over time (baseline - 3, 6 and 12 months) in a longitudinal view
timeFrame: (baseline - 3, 6 and 12 months) in a longitudinal view
measure: the change of SF-36 over time
timeFrame: baseline - 3, 6 and 12 months
measure: AF burden measured as percentage of time in AF during 7 day Holter ECG monitoring
timeFrame: at 6 months
measure: Incidence of AF recurrence
timeFrame: at 3, 6 and 12 months
measure: N-terminal-proBNP plasma levels
timeFrame: at 6 months
Other outcomes:
Locations:
city: Coburg
country: Germany
facility: Regiomed Klinikum
state: Bayern
city: Gießen
country: Germany
facility: University Hospital Gießen
state: Hessen
city: Münster
country: Germany
facility: Universitätsklinikum Münster
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: Heart Center Dresden University Hospital
state: Sachsen
city: Berlin
country: Germany
facility: German Heart Center of Charité University Medicine
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
Study officials:
affiliation: University of Leipzig
name: Rolf Wachter, Prof. Dr.
role: STUDY_CHAIR
References: