Heart Failure, Recurrent Atrial Fibrillation
Conditions
Keywords
Heart Failure
Brief summary
A streamlined AF ablation procedure done without PV mapping as a daycase is more effective than anti-arrhythmic drugs at reducing all hospital episodes for recurrent atrial fibrillation.
Detailed description
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.
Interventions
PROCEDUREAVATAR-AF ablation
Experimental ablation protocol
DRUGAnti-Arrhythmic therapy
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.
PROCEDUREConventional AF ablation
Conventional ablation procedure
Sponsors
Imperial College London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 3-Conventional AF Ablation This will involve an ablation procedure carried out in the usual manner. The patient will have three sheaths placed in the leg veins. Catheters will be passed up to the patient's heart from these veins. Two crossing are required into the left atrium. The ablation will involve freeze technology using the Advance Cryoballoon. It will include measuring the electrical signals and may also involve radiofrequency or 'burning' technology in addition.
Conventional AF ablation: Conventional ablation procedure | 108 |
| Group 2-Anti-arrhythmic Therapy Anti-arrhythmic drugs: On the treatment start date the patient will have a new tablet prescribed or a change in the dosage of the medication. The patient will be reviewed at 8wks (visit 1) later to see if the medication is working. If the tablets are working, the patients medication will be left unchanged. If not, an alternative tablet or a higher dose will be used.
Anti-Arrhythmic therapy: 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. | 103 |
| Group 1-AVATAR-AF Ablation Protocol AF ablation with pulmonary vein isolation. The patient will have two sheaths in their leg veins instead of the usual three sheaths. Catheters will be passed up to the heart from these leg veins. The single crossing into the left atrium will be by the usual method. Veins will be ablated using freeze technology known as the Advance Cryoballoon. After the ablation is completed the patient will have scans on their heart and checks of the leg veins. If all the checks are satisfactory at six hours after the procedure the patient will be allowed to go home on the same day. The patient will be reviewed in clinic in 8 weeks (visit 1) after the procedure and if it has been successful, will be reviewed again a month later (visit 2) and if all is well, the patient will be discharged from clinic.
AVATAR-AF ablation: Experimental ablation protocol | 110 |
| Total | 321 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 6 | 2 |
Baseline characteristics
| Characteristic | Total | Group 1-AVATAR-AF Ablation Protocol | Group 2-Anti-arrhythmic Therapy | Group 3-Conventional AF Ablation |
|---|---|---|---|---|
| Age, Continuous | 60.1 years STANDARD_DEVIATION 10.57 | 60.1 years STANDARD_DEVIATION 9 | 60.5 years STANDARD_DEVIATION 10.34 | 59.7 years STANDARD_DEVIATION 12.22 |
| BMI (Body Mass Index) | 28.68 kg/m^2 STANDARD_DEVIATION 4.86 | 29.12 kg/m^2 STANDARD_DEVIATION 5.04 | 27.98 kg/m^2 STANDARD_DEVIATION 4.83 | 28.88 kg/m^2 STANDARD_DEVIATION 4.67 |
| CHADSVASc Score (congestive heart failure, hypertension) 0 | 114 Participants | 35 Participants | 36 Participants | 43 Participants |
| CHADSVASc Score (congestive heart failure, hypertension) 1 | 76 Participants | 30 Participants | 24 Participants | 22 Participants |
| CHADSVASc Score (congestive heart failure, hypertension) 2 | 70 Participants | 28 Participants | 19 Participants | 23 Participants |
| CHADSVASc Score (congestive heart failure, hypertension) 3 | 39 Participants | 12 Participants | 17 Participants | 10 Participants |
| CHADSVASc Score (congestive heart failure, hypertension) 4 | 14 Participants | 4 Participants | 4 Participants | 6 Participants |
| CHADSVASc Score (congestive heart failure, hypertension) 5 | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| CHADSVASc Score (congestive heart failure, hypertension) 6 | 3 Participants | 0 Participants | 1 Participants | 2 Participants |
| Ejection Fraction | 57.8 % STANDARD_DEVIATION 5.18 | 57.1 % STANDARD_DEVIATION 4.88 | 57.9 % STANDARD_DEVIATION 5.6 | 58.3 % STANDARD_DEVIATION 5 |
| No. with Hypertension Hypertensive | 103 Participants | 38 Participants | 36 Participants | 29 Participants |
| No. with Hypertension Non-Hypertensive | 218 Participants | 72 Participants | 67 Participants | 79 Participants |
| Race/Ethnicity, Customized Ethnicity Asian | 4 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Ethnicity Black | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Ethnicity Chinese | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity Mixed | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity Other | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity White | 312 Participants | 108 Participants | 100 Participants | 104 Participants |
| Sex: Female, Male Female | 134 Participants | 46 Participants | 46 Participants | 42 Participants |
| Sex: Female, Male Male | 187 Participants | 64 Participants | 57 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 108 | 1 / 103 | 0 / 110 |
| other Total, other adverse events | 43 / 108 | 50 / 103 | 57 / 110 |
| serious Total, serious adverse events | 16 / 108 | 12 / 103 | 13 / 110 |
Outcome results
Primary
All Hospital Episodes (Emergency Room or Patient Request for OPD) Related to Treatment for Atrial Arrhythmia
Composite outcome measure - Hospital episodes (Emergency Room or Patient Request for OPD) Related to Treatment for Atrial Arrhythmia
Time frame: 12 months
Population: All randomized participants are eligible for ITT analysis - however, any patients that withdraw prior to first intervention cannot be assessed for the time-to-event based analysis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 3-Conventional AF Ablation | All Hospital Episodes (Emergency Room or Patient Request for OPD) Related to Treatment for Atrial Arrhythmia | 19 Participants |
| Group 2-Anti-arrhythmic Therapy | All Hospital Episodes (Emergency Room or Patient Request for OPD) Related to Treatment for Atrial Arrhythmia | 76 Participants |
| Group 1-AVATAR-AF Ablation Protocol | All Hospital Episodes (Emergency Room or Patient Request for OPD) Related to Treatment for Atrial Arrhythmia | 23 Participants |
Comparison: Primary Analysis - AVATAR-AF vs Anti-Arrhythmic Therapyp-value: <0.000195% CI: [0.097, 0.25]Log Rank
Comparison: Secondary analysis of Primary Outcome measure - AVATAR-AF vs Conventional Ablationp-value: 0.606195% CI: [0.639, 2.154]Log Rank
Secondary
All Hospital Episodes Which Result in a Change in Therapy for Atrial Arrhythmia
Composite outcome measure - All hospital episodes which result in a change in therapy for atrial arrhythmia
Time frame: 12 months
Secondary
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)
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)
Time frame: 12 months
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 3-Conventional AF Ablation | 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) | All Events | 3 participants |
| Group 3-Conventional AF Ablation | 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) | Drug Side Effect/Allergic Reaction | 1 participants |
| Group 3-Conventional AF Ablation | 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) | Vascular Complication | 1 participants |
| Group 3-Conventional AF Ablation | 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) | Cardiac Tamponade | 0 participants |
| Group 3-Conventional AF Ablation | 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) | Phrenic Nerve Palsy | 0 participants |
| Group 3-Conventional AF Ablation | 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) | TIA | 1 participants |
| Group 2-Anti-arrhythmic Therapy | 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) | TIA | 1 participants |
| Group 2-Anti-arrhythmic Therapy | 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) | All Events | 19 participants |
| Group 2-Anti-arrhythmic Therapy | 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) | Cardiac Tamponade | 0 participants |
| Group 2-Anti-arrhythmic Therapy | 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) | Phrenic Nerve Palsy | 0 participants |
| Group 2-Anti-arrhythmic Therapy | 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) | Drug Side Effect/Allergic Reaction | 18 participants |
| Group 2-Anti-arrhythmic Therapy | 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) | Vascular Complication | 0 participants |
| Group 1-AVATAR-AF Ablation Protocol | 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) | Drug Side Effect/Allergic Reaction | 2 participants |
| Group 1-AVATAR-AF Ablation Protocol | 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) | Vascular Complication | 3 participants |
| Group 1-AVATAR-AF Ablation Protocol | 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) | TIA | 0 participants |
| Group 1-AVATAR-AF Ablation Protocol | 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) | Cardiac Tamponade | 2 participants |
| Group 1-AVATAR-AF Ablation Protocol | 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) | All Events | 7 participants |
| Group 1-AVATAR-AF Ablation Protocol | 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) | Phrenic Nerve Palsy | 0 participants |
Secondary
Death or Stroke From Any Cause
Composite outcome measure
Time frame: 12 months
Population: Full ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 3-Conventional AF Ablation | Death or Stroke From Any Cause | 0 Participants |
| Group 2-Anti-arrhythmic Therapy | Death or Stroke From Any Cause | 1 Participants |
| Group 1-AVATAR-AF Ablation Protocol | Death or Stroke From Any Cause | 0 Participants |