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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/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] 0 0
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 0 0
Pulmonary Vein Isolation 0 0
Dormant Pulmonary Vein Conduction 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
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] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Between 3 and 12 months post ablation
Secondary outcome [1] 0 0
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] 0 0
between 3 and 12 months
Secondary outcome [2] 0 0
Repeat ablation procedure for documented recurrence of symptomatic AF or atrial flutter/tachycardia.
Timepoint [2] 0 0
between 3 and 12 months
Secondary outcome [3] 0 0
Emergency visits or hospitalizations
Timepoint [3] 0 0
between 0 and 12 months
Secondary outcome [4] 0 0
Antiarrhythmic drug use because of documented recurrence of symptomatic AF or atrial flutter/tachycardia
Timepoint [4] 0 0
between 0 and 12 months
Secondary outcome [5] 0 0
Proportion of patients with AF or left atrial flutter/tachycardia occurring during the first 90 days post ablation
Timepoint [5] 0 0
between 0 and 3 months
Secondary outcome [6] 0 0
Major peri-procedural complications including stroke, PV stenosis, cardiac perforation, atrio-esophageal fistulae, and death
Timepoint [6] 0 0
between 0 and 12 months
Secondary outcome [7] 0 0
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] 0 0
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
Gender
Both males and females
Can healthy volunteers participate?
No
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Linz
Country [2] 0 0
Belgium
State/province [2] 0 0
Bruxelles
Country [3] 0 0
Canada
State/province [3] 0 0
Alberta
Country [4] 0 0
Canada
State/province [4] 0 0
British Columbia
Country [5] 0 0
Canada
State/province [5] 0 0
Nova Scotia
Country [6] 0 0
Canada
State/province [6] 0 0
Ontario
Country [7] 0 0
Canada
State/province [7] 0 0
Quebec
Country [8] 0 0
France
State/province [8] 0 0
Bordeaux
Country [9] 0 0
Germany
State/province [9] 0 0
Eppendorf
Country [10] 0 0
Germany
State/province [10] 0 0
Muenchen
Country [11] 0 0
Germany
State/province [11] 0 0
Bad Krozingen

Funding & Sponsors
Primary sponsor type
Other
Name
Montreal Heart Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Canadian Institutes of Health Research (CIHR)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Abbott Medical Devices
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Commercial sector/Industry
Name [3] 0 0
Johnson & Johnson
Address [3] 0 0
Country [3] 0 0

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/show/NCT01058980
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Laurent Macle, MD
Address 0 0
Montreal Heart Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications