ADenosine Following Pulmonary Vein Isolation to Target Dormant Conduction Elimination: the ADVICE Trial (ADVICE)
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|ClinicalTrials.gov Identifier: NCT01058980|
Recruitment Status : Completed
First Posted : January 29, 2010
Last Update Posted : April 3, 2014
|Condition or disease||Intervention/treatment||Phase|
|Paroxysmal Atrial Fibrillation Pulmonary Vein Isolation Dormant Pulmonary Vein Conduction||Procedure: Additional ablation until elimination of dormant conduction Procedure: No additional ablation Procedure: Registry group Procedure: Usual medical care||Phase 4|
Atrial fibrillation (AF), the most frequently treated cardiac arrhythmia, impairs quality of life and increases stroke risk and mortality. Despite advances in antiarrhythmic drug therapy, AF remains uncontrolled in many patients. More effective measures to prevent, treat and potentially cure AF are needed. Ectopic foci originating from pulmonary veins (PVs) initiate AF in many patients. PV isolation (PVI), in which PV conduction is eliminated by catheter ablation, has emerged as an effective treatment in selected patients. However AF recurs in up to 50%, due to recovery of PV conduction. Dormant PV conduction (PV conduction suppressed at time of PVI with subsequent recovery) has been proposed to explain recurrences. We demonstrated that adenosine can restore conduction in viable PVs after attempted PVI by activating outward K+-currents, leading to selective hyperpolarization of PV cardiomyocytes and removal of voltage-dependent Na+-channel inactivation. Thus, adenosine can be used to differentiate permanent PV-atrial block from dormant PV conduction and to identify the need for additional ablation. We recently performed a pilot study in 47 patients, in whom adenosine was used to guide additional ablation. Results were compared to 47 historical controls. Dormant conduction was observed in 55% of patients undergoing PVI and additional adenosine-guided ablation decreased the AF recurrence rate from 49% to 21%. An adequately-powered prospective randomized controlled clinical trial is required to confirm these findings.
The primary objective of the proposed ADVICE trial is to evaluate the impact of adenosine-guided PVI in preventing AF recurrences among patients with paroxysmal AF. We hypothesize that a PVI ablation strategy that incorporates elimination of dormant conduction unmasked by intravenous adenosine will decrease symptomatic AF recurrence compared to standard PVI, without incurring significant additional risk. This prospective randomized study will be conducted at 15 clinical centers in Canada, Europe and Australia. Patients with paroxysmal AF referred for PVI will be recruited. Standard PVI will be performed in all patients until elimination of PV conduction. All patients will subsequently receive intravenous adenosine in an attempt to unmask dormant conduction. If dormant conduction is elicited, patients will be randomized to no further ablation (Group 1; control) or additional adenosine-guided ablation until dormant conduction is abolished (Group 2; adenosine-guided PVI). If no dormant conduction is revealed, randomly selected patients will be followed in a registry to further assess the role of dormant conduction as a predictor of AF recurrence. Portable electrocardiographic monitors will be provided to all patients. The primary outcome will be the time to first documented symptomatic AF episode post-PVI based on an intention-to-treat analysis. Since symptomatic AF recurrence is anticipated in 45% of controls, 210 patients with dormant conduction are required in order to be able to detect a difference of 20%, with a power of at least 85%. Assuming the presence of dormant conduction in a minimum of 40% of patients after standard PVI, 526 patients will be enrolled in the study. Enrolment is expected to be completed within 12 months, with all patients followed for 12 months.
Demonstrated superiority of an adenosine-guided PVI ablation strategy would represent a major advancement in refining the interventional approach for AF. The ADVICE trial carries the potential, therefore, to alter the standard of care and benefit patients with AF by reducing arrhythmia recurrence, hospitalizations and the need for repeat interventions
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||550 participants|
|Intervention Model:||Parallel Assignment|
|Official Title:||ADenosine Following Pulmonary Vein Isolation to Target Dormant Conduction Elimination: the ADVICE Trial|
|Study Start Date :||December 2009|
|Actual Primary Completion Date :||September 2013|
|Actual Study Completion Date :||December 2013|
Active Comparator: Dormant PV conduction
After PVI, dormant conduction will be evaluated using intravenous adenosine. If dormant conduction is present, the patients will be randomized to two parallel groups:
Procedure: Additional ablation until elimination of dormant conduction
Additional RF energy will be delivered at sites of re-conduction on the circular mapping catheter in each PV. Abolition of the dormant conduction will then be assessed by repeated injections of adenosine using the same doses previously used to reveal dormant conduction. Additional ablation as described will be performed until re-injection of adenosine shows no re-conduction in any of the PV.
Procedure: No additional ablation
Presence of dormant PV conduction, no additional ablation.
Active Comparator: No dormant PV conduction
If no dormant conduction is documented, patients will be selected in a random fashion to be included in a registry (follow-up as planned for group 1 and 2 above). The registry group will allow for further assessment of the role of dormant conduction as a predictor of AF recurrence by comparing the success rate after ablation in patients without dormant conduction with those of Group 1 and 2.
Procedure: Registry group
Among those who will be found not to have the presence of dormant conduction, and within each site, three-quarters of the patients will be randomly selected to be included in the registry group.
Procedure: Usual medical care
Clinical follow-up will be performed according to the regular follow-up after AF ablation procedures in each of the participating centers. No data will be collected after discharge.One-fourth of the patients will be randomly selected to be included in the usual medical care group.
- Time to first recurrence of electrocardiographically documented, symptomatic AF or atrial flutter/tachycardia between 3 and 12 months post ablation in the absence of antiarrhythmic drug therapy. [ Time Frame: Between 3 and 12 months post ablation ]The primary outcome is time to first recurrence of symptomatic ECG-documented AF or atrial flutter/tachycardia between days 91 & 365 after ablation, or repeat ablation procedure during the first 90 days. AF or atrial flutter/tachycardia will qualify as an arrhythmia recurrence after ablation if it lasts 30 seconds or longer and is documented by 12-lead ECG, surface ECG rhythm strips, or TTM recordings. Documented episodes will be adjudicated by a blinded committee. Time 0 is defined as day 91 post ablation with FUp's extending 365 days post ablation.
- Time to first recurrence of any electrocardiographically documented AF or atrial flutter/tachycardia (symptomatic or asymptomatic) between days 91 and 365 after ablation. [ Time Frame: between 3 and 12 months ]
- Repeat ablation procedure for documented recurrence of symptomatic AF or atrial flutter/tachycardia. [ Time Frame: between 3 and 12 months ]
- Emergency visits or hospitalizations [ Time Frame: between 0 and 12 months ]
- Antiarrhythmic drug use because of documented recurrence of symptomatic AF or atrial flutter/tachycardia [ Time Frame: between 0 and 12 months ]
- Proportion of patients with AF or left atrial flutter/tachycardia occurring during the first 90 days post ablation [ Time Frame: between 0 and 3 months ]
- Major peri-procedural complications including stroke, PV stenosis, cardiac perforation, atrio-esophageal fistulae, and death [ Time Frame: between 0 and 12 months ]
- Generic and disease specific quality of life (assessed by the Cardiovascular Society Severity in AF (CCS-SAF) scale and SF-36 questionnaire at baseline, and at 3, 6 and 12 months post randomization). [ Time Frame: between 0 and 12 months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01058980
|Principal Investigator:||Laurent Macle, MD||Montreal Heart Institute|