ADenosine Following Pulmonary Vein Isolation to Target Dormant Conduction Elimination: the ADVICE Trial

NCT01058980 | Completed Phase 4 DMC

• 1 other identifier: ICM 08-1067
• Study Type: interventional
• Target: 550
• Locations: 5 countries
• Sites: 17

Brief Summary

Atrial fibrillation (AF) is the most common heart rhythm disorder, impairs quality of life and increases stroke risk and mortality. Despite advances in medical treatment, AF remains uncontrolled in many patients. In many patients, AF is initiated by abnormal electrical impulses from the pulmonary veins. A catheter ablation procedure called pulmonary vein isolation (PVI) has therefore been developed, using heat to isolate the PV foci from the heart. PVI is very effective, but must be repeated in up to 50% of cases because the foci isolation is not permanent after initial PVI. The intravenous administration of a drug called adenosine during the PVI procedure can unmask residual conduction that would otherwise remain unnoticed, so-called "dormant conduction". In our experience, additional ablation guided by adenosine reduces AF recurrence and the need for a repeat PVI procedure. However, the adenosine-guided approach has not yet been proven as standard therapy. The present study, to be conducted at 15 clinical centres in Canada, Europe and Australia is therefore intended to evaluate the efficacy of adenosine-guided ablation to prevent AF recurrence. Five hundred twenty-six patients will be included in the study, which should be completed within 2 years. In all patients, the presence of dormant conduction will be tested with adenosine during PVI. If dormant conduction is observed, additional ablation will be performed in half of these patients selected randomly. If there is no dormant conduction, randomly selected patients will be followed in a registry. If the adenosine-guided approach is demonstrated to improve the success rate of PVI procedures, it should become the standard approach for a "permanent cure" of AF, and therefore benefit patients by reducing arrhythmia recurrence, hospitalizations and the need for repeat interventions.

Conditions

Paroxysmal Atrial Fibrillation; Pulmonary Vein Isolation; Dormant Pulmonary Vein Conduction

Keywords

catheter ablation; atrial fibrillation; adenosine

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  Between 3 and 12 months post ablation

Secondary Outcomes (7)

• Time to first recurrence of any electrocardiographically documented AF or atrial flutter/tachycardia (symptomatic or asymptomatic) between days 91 and 365 after ablation.

  between 3 and 12 months

• Repeat ablation procedure for documented recurrence of symptomatic AF or atrial flutter/tachycardia.

  between 3 and 12 months

• Emergency visits or hospitalizations

  between 0 and 12 months

• Antiarrhythmic drug use because of documented recurrence of symptomatic AF or atrial flutter/tachycardia

  between 0 and 12 months

• Proportion of patients with AF or left atrial flutter/tachycardia occurring during the first 90 days post ablation

  between 0 and 3 months

Study Arms (2)

Dormant PV conduction

ACTIVE COMPARATOR

After PVI, dormant conduction will be evaluated using intravenous adenosine. If dormant conduction is present, the patients will be randomized to two parallel groups: * Group 1: No additional ablation * Group 2: Additional ablation until elimination of dormant conduction.

Procedure: Additional ablation until elimination of dormant conduction; Procedure: No additional ablation

No dormant PV conduction

ACTIVE COMPARATOR

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; Procedure: Usual medical care

Interventions

Additional ablation until elimination of dormant conduction PROCEDURE

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.

Dormant PV conduction

No additional ablation PROCEDURE

Presence of dormant PV conduction, no additional ablation.

Dormant PV conduction

Registry group PROCEDURE

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.

No dormant PV conduction

Usual medical care PROCEDURE

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.

No dormant PV conduction

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age more than 18 years
• Paroxysmal AF for at least 6 months with at least 3 symptomatic episodes (using patient history) during the previous 6 months
• Patients must be felt to be candidates for AF ablation based on AF that is symptomatic and refractory or intolerant to at least one class 1 or 3 antiarrhythmic agent.
• Documentation of at least one episode of AF on 12 lead ECG, TTM or Holter monitor within 12 months of randomization in the trial
• Patients must be on continuous anticoagulation with warfarin (INR 2-3) or fractionated subcutaneous heparin for \>4 weeks prior to the ablation or they have undergone a recent (less than 48 hours before planned ablation) transoesophageal echocardiogram to exclude left atrial thrombus.
• Patients must provide written informed consent to participate in the clinical trial.

You may not qualify if:

• Contraindications to oral anticoagulants
• History of any previous ablation or surgical maze for AF
• Intracardiac thrombus
• AF due to reversible cause
• Patients with left atrial size \> 55mm or significant mitral valve disease (moderate or severe mitral stenosis or regurgitation)
• Pregnancy
• Asthma, history of bronchospasm or known adverse reaction to adenosine

Sponsors & Collaborators

• Montreal Heart Institute: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Abbott Medical Devices: collaborator
• Johnson & Johnson: collaborator

Study Sites (18)

Royal Perth Hospital

Perth, Western Australia, Australia

Location

KH d. Elisabethinen Linz GmbH

Linz, Linz, A-4010, Austria

Location

Cliniques universitaires Saint-Luc

Brussels, Brussels Capital, Belgium

Location

Foothills Medical Center

Calgary, Alberta, T2N 2T9, Canada

Location

Royal Jubilee Hospital

Vancouver, British Columbia, V8R 4R2, Canada

Location

QE II Health Sciences Center

Halifax, Nova Scotia, B3H 3A7, Canada

Location

McMaster University and Hamilton Health Sciences

Hamilton, Ontario, L8L 2X2, Canada

Location

London Health Science Centers

London, Ontario, N6A 5W9, Canada

Location

Southlake Regional Health Center

Newmarket, Ontario, L3Y 2P9, Canada

Location

Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

Location

Montreal General Hospital

Montreal, Quebec, H3G 1A4, Canada

Location

Montreal Heart Institute

Montreal, Quebec, HIT IC8, Canada

Location

Institut universitaire de cardiologie et de pneumologie de Québec

Québec, Quebec, Canada

Location

Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, Canada

Location

Hôpital Cardiologique du Haut-Lévêque

Bordeaux, Bordeaux, 33604, France

Location

Herz-Zentrum Bad Krozingen

Bad Krozingen, Bad Krozingen, 79189, Germany

Location

University Heart Center

Hamburg, Eppendorf, Germany

Location

Deutsches Herzzentrum Muenchen

Munich, Muenchen, D-80636, Germany

Location

Related Publications (4)

• Willems S, Khairy P, Andrade JG, Hoffmann BA, Levesque S, Verma A, Weerasooriya R, Novak P, Arentz T, Deisenhofer I, Rostock T, Steven D, Rivard L, Guerra PG, Dyrda K, Mondesert B, Dubuc M, Thibault B, Talajic M, Roy D, Nattel S, Macle L; ADVICE Trial Investigators*. Redefining the Blanking Period After Catheter Ablation for Paroxysmal Atrial Fibrillation: Insights From the ADVICE (Adenosine Following Pulmonary Vein Isolation to Target Dormant Conduction Elimination) Trial. Circ Arrhythm Electrophysiol. 2016 Aug;9(8):e003909. doi: 10.1161/CIRCEP.115.003909.

  PMID: 27516462 DERIVED

• Macle L, Khairy P, Weerasooriya R, Novak P, Verma A, Willems S, Arentz T, Deisenhofer I, Veenhuyzen G, Scavee C, Jais P, Puererfellner H, Levesque S, Andrade JG, Rivard L, Guerra PG, Dubuc M, Thibault B, Talajic M, Roy D, Nattel S; ADVICE trial investigators. Adenosine-guided pulmonary vein isolation for the treatment of paroxysmal atrial fibrillation: an international, multicentre, randomised superiority trial. Lancet. 2015 Aug 15;386(9994):672-9. doi: 10.1016/S0140-6736(15)60026-5. Epub 2015 Jul 23.

  PMID: 26211828 DERIVED

• Andrade JG, Pollak SJ, Monir G, Khairy P, Dubuc M, Roy D, Talajic M, Deyell M, Rivard L, Thibault B, Guerra PG, Nattel S, Macle L. Pulmonary vein isolation using a pace-capture-guided versus an adenosine-guided approach: effect on dormant conduction and long-term freedom from recurrent atrial fibrillation--a prospective study. Circ Arrhythm Electrophysiol. 2013 Dec;6(6):1103-8. doi: 10.1161/CIRCEP.113.000454. Epub 2013 Oct 4.

  PMID: 24097372 DERIVED

• Macle L, Khairy P, Verma A, Weerasooriya R, Willems S, Arentz T, Novak P, Veenhuyzen G, Scavee C, Skanes A, Puererfellner H, Jais P, Khaykin Y, Rivard L, Guerra PG, Dubuc M, Thibault B, Talajic M, Roy D, Nattel S; ADVICE Study Investigators. Adenosine following pulmonary vein isolation to target dormant conduction elimination (ADVICE): methods and rationale. Can J Cardiol. 2012 Mar-Apr;28(2):184-90. doi: 10.1016/j.cjca.2011.10.008. Epub 2012 Jan 2.

  PMID: 22217936 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Laurent Macle, MD

  Montreal Heart Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair, ADVICE Study

Study Record Dates

• First Submitted: January 28, 2010
• First Posted: January 29, 2010
• Study Start: December 1, 2009
• Primary Completion: September 1, 2013
• Study Completion: December 1, 2013
• Last Updated: April 3, 2014

Record last verified: 2014-04

Locations

CA (11); BE (1); AU (1); FR (1); DE (3)