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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01058980

Registration number

NCT01058980

Ethics application status

Date submitted

28/01/2010

Date registered

29/01/2010

Date last updated

3/04/2014

Titles & IDs

Public title

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

Scientific title

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

Secondary ID [1]

ICM 08-1067

Universal Trial Number (UTN)

Trial acronym

ADVICE

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Paroxysmal Atrial Fibrillation

Pulmonary Vein Isolation

Dormant Pulmonary Vein Conduction

Condition category

Condition code

Cardiovascular

Other cardiovascular diseases

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Surgery - Additional ablation until elimination of dormant conduction
Treatment: Surgery - No additional ablation
Treatment: Surgery - Registry group
Treatment: Surgery - Usual medical care

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:

* Group 1: No additional ablation
* Group 2: Additional ablation until elimination of dormant conduction.

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.

Treatment: Surgery: 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.

Treatment: Surgery: No additional ablation
Presence of dormant PV conduction, no additional ablation.

Treatment: Surgery: 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.

Treatment: Surgery: 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.

Intervention code [1]

Treatment: Surgery

Comparator / control treatment

Control group

Outcomes

Primary outcome [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.

Timepoint [1]

Between 3 and 12 months post ablation

Secondary outcome [1]

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

Timepoint [1]

between 3 and 12 months

Secondary outcome [2]

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

Timepoint [2]

between 3 and 12 months

Secondary outcome [3]

Emergency visits or hospitalizations

Timepoint [3]

between 0 and 12 months

Secondary outcome [4]

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

Timepoint [4]

between 0 and 12 months

Secondary outcome [5]

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

Timepoint [5]

between 0 and 3 months

Secondary outcome [6]

Major peri-procedural complications including stroke, PV stenosis, cardiac perforation, atrio-esophageal fistulae, and death

Timepoint [6]

between 0 and 12 months

Secondary outcome [7]

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).

Timepoint [7]

between 0 and 12 months

Eligibility

Key inclusion criteria

* 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.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

* 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

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s

Intervention assignment

Parallel

Other design features

Phase

Phase 4

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

1/12/2009

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

1/12/2013

Sample size

Target

Accrual to date

Final

550

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

Royal Perth Hospital - Perth

Recruitment postcode(s) [1]

- Perth

Recruitment outside Australia

Country [1]

Austria

State/province [1]

Linz

Country [2]

Belgium

State/province [2]

Bruxelles

Country [3]

Canada

State/province [3]

Alberta

Country [4]

Canada

State/province [4]

British Columbia

Country [5]

Canada

State/province [5]

Nova Scotia

Country [6]

Canada

State/province [6]

Ontario

Country [7]

Canada

State/province [7]

Quebec

Country [8]

France

State/province [8]

Bordeaux

Country [9]

Germany

State/province [9]

Eppendorf

Country [10]

Germany

State/province [10]

Muenchen

Country [11]

Germany

State/province [11]

Bad Krozingen

Funding & Sponsors

Primary sponsor type

Other

Name

Montreal Heart Institute

Address

Country

Other collaborator category [1]

Government body

Name [1]

Canadian Institutes of Health Research (CIHR)

Address [1]

Country [1]

Other collaborator category [2]

Commercial sector/industry

Name [2]

Abbott Medical Devices

Address [2]

Country [2]

Other collaborator category [3]

Commercial sector/industry

Name [3]

Johnson & Johnson

Address [3]

Country [3]

Ethics approval

Ethics application status

Summary

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.

Trial website

https://clinicaltrials.gov/study/NCT01058980

Trial related presentations / publications

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.
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.
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. Erratum In: Circ Arrhythm Electrophysiol. 2015 Feb;8(1):247. doi: 10.1161/HAE.0000000000000010.
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.

Public notes

Contacts

Principal investigator

Name

Laurent Macle, MD

Address

Montreal Heart Institute

Country

Phone

Fax

Contact person for public queries

Name

Address

Country

Phone

Fax

Contact person for scientific queries

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT01058980

Trial Review

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01058980