Ablation Verses Anti-arrhythmic Therapy for Reducing All Hospital Episodes From Recurrent Atrial Fibrillation

AVATAR-AF is a multicentre, randomised controlled study comparing a streamlined AVATAR-protocol ablation procedure to anti-arrhythmic therapy in patients with documented paroxysmal AF who are considered to be failing current strategy for AF. A secondary control arm will also compare the AVATAR-protocol to conventional AF ablation. 300 patients who are on no prior anti-arrhythmic, 'pill-in-pocket' or taking regular anti-arrhythmics will be randomised in a 1:1:1 manner to a treatment strategy of either AVATAR-protocol ablation, anti-arrhythmic therapy or conventional AF ablation and followed-up for 1 year.

• AVATAR-AF ablation (Procedure), also known as Ablation method-surgical: Experimental ablation protocol
• Anti-Arrhythmic therapy (Drug), also known as Amiodarone, Dronaderone, Sotalol, Beta blockers, Calcium channel blockers, Flecainide, Propafenone: Group 2 will be prescribed medication listed below: Amiodarone; Dronaderone; Sotalol Beta blockers; Calcium channel blockers; Flecainide; or Propafenone. You will then be discharged from clinic. A research nurse will contact you by phone to make sure there are no problems and can make hospital appointments if needed.
• Conventional AF ablation (Procedure), also known as Ablation method-surgical: Conventional ablation procedure

Primary outcomes

• All Hospital Episodes (Emergency Room or Patient Request for OPD) Related to Treatment for Atrial Arrhythmia [12 months]: Composite outcome measure - Hospital episodes (Emergency Room or Patient Request for OPD) Related to Treatment for Atrial Arrhythmia

Secondary outcomes

• Death or Stroke From Any Cause [12 months]: Composite outcome measure
• Any Complications Caused by the Procedure (Pericardial Effusion, Bleeding >2 Units, Phrenic Nerve Palsy and Other) or the Anti-arrhythmic Drug (GI Disturbance, Skin Irritation and Other) [12 months]: Composite outcome measure - Caused by the Procedure (Pericardial Effusion, Bleeding >2 Units, Phrenic Nerve Palsy and Other) or the Anti-arrhythmic Drug (GI Disturbance, Skin Irritation and Other)
• All Hospital Episodes Which Result in a Change in Therapy for Atrial Arrhythmia [12 months]: Composite outcome measure - All hospital episodes which result in a change in therapy for atrial arrhythmia

Sex: All, ages: 18 Years to 80 Years

Inclusion Criteria:

1. Documented paroxysmal atrial fibrillation
2. Modification or initiation of anti-arrhythmic agent required for symptom control
3. Males or females eighteen (18) to eighty (80) years of age
4. Suitable candidate for catheter ablation
5. Signed informed consent

Exclusion Criteria:

1. Contraindication to catheter ablation
2. No carer to enable daycase discharge
3. Arrhythmias other than AF documented unless they have had curative ablation (eg. for atrial flutter)
4. No documentation of sinus rhythm within 3 months
5. Valvular or coronary heart disease needing regular follow up
6. EF <45% or moderate/severe LV dysfunction
7. Active gastrointestinal disease
8. Renal failure with creatinine >200 μmol/L or on dialysis
9. Active fever or infection
10. Life expectancy shorter than the trial
11. Allergy to contrast
12. Severe cerebrovascular disease
13. Bleeding or clotting disorders or inability to receive heparin
14. Uncontrolled diabetes (HbA1c ≥73 mmol/mol or HbA1c ≤64 mmol/mol and Fasting Blood Glucose ≥9.2 mmol/L)
15. Serum Potassium \[K+\] <3.5 mmol/L or >5.0 mmol/L
16. Malignancy needing surgery, chemotherapy or radiotherapy
17. Pregnancy or women of child-bearing potential not using a highly effective method of contraception
18. Must not have previous (4 weeks prior to screening) or current participation in another clinical trial with an investigational drug or investigational device
19. Unable to give informed consent
20. Uncontrolled thyroid disease defined as abnormal thyroid function tests causing cardiac manifestations within the last 6mths
21. Unable to attend follow up visits

Participant flow

Outcome results

• All Hospital Episodes (Emergency Room or Patient Request for OPD) Related to Treatment for Atrial Arrhythmia (Primary), Count of participants, Participants: Group 3-Conventional AF Ablation 19; Group 2-Anti-arrhythmic Therapy 76; Group 1-AVATAR-AF Ablation Protocol 23 (p <0.0001)
• Death or Stroke From Any Cause (Secondary), Count of participants, Participants: Group 3-Conventional AF Ablation 0; Group 2-Anti-arrhythmic Therapy 1; Group 1-AVATAR-AF Ablation Protocol 0
• Any Complications Caused by the Procedure (Pericardial Effusion, Bleeding >2 Units, Phrenic Nerve Palsy and Other) or the Anti-arrhythmic Drug (GI Disturbance, Skin Irritation and Other) (Secondary), Number, participants: Group 3-Conventional AF Ablation 3; Group 2-Anti-arrhythmic Therapy 19; Group 1-AVATAR-AF Ablation Protocol 7
• All Hospital Episodes Which Result in a Change in Therapy for Atrial Arrhythmia (Secondary)

Adverse events

Time frame: AE's are collected from Randomization up to 1-year end-of-Study Visit

Serious adverse events by term

Other adverse events by term

• Results publication: Kanagaratnam P, McCready J, Tayebjee M, Shepherd E, Sasikaran T, Todd D, Johnson N, Kyriacou A, Hayat S, Hobson NA, Mann I, Balasubramaniam R, Whinnett Z, Earley M, Petkar S, Veasey R, Kirubakaran S, Coyle C, Kim MY, Lim PB, O'Neill J, Davies DW, Peters NS, Babalis D, Linton N, Falaschetti E, Tanner M, Shah J, Poulter N. Ablation versus anti-arrhythmic therapy for reducing all hospital episodes from recurrent atrial fibrillation: a prospective, randomized, multi-centre, open label trial. Europace. 2023 Mar 30;25(3):863-872. doi: 10.1093/europace/euac253. PMID 36576323
• Results publication: Mann I, Sasikaran T, Sandler B, Babalis D, Johnson N, Falaschetti E, Copley A, Tayebjee M, Todd D, Shepherd E, McCready J, Poulter N F, Kanagaratnam P. Ablation versus Anti-Arrhythmic Therapy for Reducing All Hospital Episodes from Recurrent Atrial Fibrillation (AVATAR-AF): Design and rationale. Am Heart J. 2019 Aug;214:36-45. doi: 10.1016/j.ahj.2019.04.015. Epub 2019 May 3. PMID 31152874

• Study Protocol (PDF, 2018-02-09)
• Statistical Analysis Plan (PDF, 2018-03-24)

• Dr. Prapa Kanagaratnam, Principal investigator, Imperial College London