Condition category
Circulatory System
Date applied
01/12/2015
Date assigned
08/12/2015
Last edited
24/03/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Atrial fibrillation (AF) is the term used to refer to a heart condition which causes an irregular and often abnormally fast heart rate (arrhythmia); in some cases the heart can beat faster than 100 beats per minute. Symptoms include feeling dizzy, being short of breath and feeling tired. Patients may also be aware of heart palpitations, where the heart feels like its pounding, fluttering or beating irregularly. The exact cause of the condition is unknown but is more common with age and effects some groups of people more than others. It is the most common cause of heart (cardiac) arrhythmia, affecting millions of people in the United States and around the world. Treating AF continues to be a challenge. Over the last 15 years, the catheter-based AF ablation procedure, which involves destroying the area of the heart causing the condition, has been widely adopted. Approximately 50% of patients treated with catheter ablation have been suffering from a persistent type of the arrhythmia. Unfortunately, ablation results in this population have been dismal, not only because of low success rates in suppressing arrhythmias, but also from a healthcare cost point of view. In fact, the long-term success of such a procedure has been reported to be as low as 20%, and patients may need more than two ablation procedures to just stop arrhythmia temporarily. A major issue contributing to the low success of catheter ablation is the lack of a protocol to appropriately select patients that would respond to this treatment. Currently, cardiologists base their decision to ablate persistent AF on various co-existing diseases (comorbidities), a concept that has not been proven successful. With the introduction of AF ablation as a first line therapy option, a better and more accurate selection protocol is urgently needed. There is a strong association between AF and atrial tissue fibrosis (thickening and scaring of tissue in the heart). Recently, a novel DE-MRI (Delayed-Enhancement MRI) based imaging technique has been shown to reveal the degree of fibrotic atrial tissue in patients suffering from AF. A number of studies have shown that the amount of atrial tissue fibrosis present is directly related to how successful the treatment is likely to be. In addition, in one study involving a number of different study sites, the best predictor for how successful the treatment is related to whether there are areas of atrial fibrosis covered by ablation lesions (scaring caused by the ablation treatment). The aim of this study is to examine how successful targeting atrial fibrosis tissue during an ablation procedure is at treating persistent AF.

Who can participate?
Adults (aged at least 18) with persistent SF.

What does the study involve?
Patients are randomized to receive either conventional pulmonary vein isolation (PVI) ablation or PVI plus fibrosis-guided ablation. All patients are then followed up for the next 18 months to assess whether there is a recurrence of the persistent abnormal heart rhythms.

What are the possible benefits and risks of participating?
Subjects in either treatment arm receiving fibrosis-guided ablation targeting atrial fibrosis may stay in a normal heart rhythm and may have fewer AA recurrences than those who receive conventional pulmonary vein isolation (PVI) ablation. The study also makes use of new technologies that allow closer and more frequent monitoring of patients’ heart rhythm. All participants will receive the mobile heart monitoring device (ECG Check) to complete regular monitoring of their heart rhythm after the ablation procedure. This may allow for earlier detection of atrial arrhythmia recurrence and may also reveal other arrhythmias of clinical significance. The second MRI scan will provide information about early post-ablation scar formation and the presence and degree of pulmonary vein stenosis (narrowing of the veins that carry oxygen-rich blood from the lungs to the heart). This information may be clinically beneficial to all participants in the study. The general risks of catheter-based ablation for AF include perforation of the heart, pulmonary vein stenosis, stroke, and bleeding or pain at the insertion site. There are also potential risks related to the fibrosis-guided ablation procedures: Due to the longer time under anesthesia, more areas being ablated and longer total procedure time, subjects in the fibrosis-guided ablation group are at greater potential risk for scarring, nerve damage, esophageal (food pipe) injury, perforation of the heart, and atrial esophageal fistulas (a rare complication in which the esophagus is damaged by the catheter used in the ablation procedure. The small amount of blood drawn for the study will pose a very small risk e.g. bleeding, pain, or hematoma/bruise at the puncture site.

Where is the study run from?
This is a multicentre, international study with trial participating sites in Spain, China, Canada, Australia, Italy, France, Netherlands and Germany.

When is the study starting and how long is it expected to run for?
April 2016 to April 2019

Who is funding the study?
1. St June Medical (USA)
2. Siemens USA
3. Medtronic (USA)

Who is the main contact?
1. Dr Christina Pacchia (public)
2. Dr Nassir Marrouche (scientific)

Trial website

Contact information

Type

Public

Primary contact

Dr Christina Pacchia

ORCID ID

Contact details

Comprehensive Arrhythmia Research and Management (CARMA) Center
Division of Cardiology
30 North 1900 East
Room 4A100
Salt Lake City
84132
United States of America

Type

Scientific

Additional contact

Dr Nassir Marrouche

ORCID ID

http://orcid.org/0000-0003-0970-9182

Contact details

Comprehensive Arrhythmia Research and Management (CARMA) Center
Division of Cardiology
30 North 1900 East
Room 4A100
Salt Lake City
84132
United States of America

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT02529319

Protocol/serial number

NCT02529319

Study information

Scientific title

Efficacy of DE-MRI-guided fibrosis ablation vs. conventional Catheter Ablation of Atrial Fibrillation: DECAAF II

Acronym

DECAAF II

Study hypothesis

We hypothesize that patients receiving fibrosis-guided ablation in addition to conventional PVI ablation will have fewer atrial arrhythmias (AA) recurrences than those who receive PVI ablation alone.

Ethics approval

University of Utah Institutional Review Board, 18/12/2015, ref: 82681

Study design

Prospective randomized multicenter trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Atrial fibrillation (AF)

Intervention

Consented patients will be randomized to one of two study groups to receive conventional PVI ablation (Group 1) or PVI + fibrosis-guided ablation (Group 2).

In Group 1 (control group), PVI ablation will be performed as recommended by the HRS consensus statement and physicians will be blinded to the pre-ablation MRI fibrosis results. The operator will create lesions around the PV antra. Entrance block in all pulmonary veins will be confirmed using standard techniques. Successful ablation is operationally defined as an abolishment of PV electrograms (EGMs). Assessment for the presence of exit block by pacing within the antral lesion set will be at the discretion of the operator. If normal sinus rhythm cannot be restored at the end of the PVI portion of the procedure despite cardioversion in patients randomized to the conventional ablation group (Group 1), the operator may pursue further measures, such as triggering ablation, to eliminate recurrent arrhythmia if needed. The creation of a right atrial cavotricuspid isthmus line is also left at the discretion of the operator.

In Group 2 (intervention arm), processed DE-MRI images will be merged with the 3D mapping system at the Clinical Center. All patients will undergo the previously described pulmonary vein isolation procedure (PVI). Pulmonary vein entrance block at the end of the ablation procedure should be confirmed and is defined as loss of pulmonary vein potentials using standard techniques. After PVI and PV entrance block have been confirmed, fibrosis-guided ablation will ensue. The operator will encircle by ablating at the perimeter of the fibrosis and ensure loss of capture in the fibrotic isolated area at 10 milli-amp stimulation, and/or completely cover all fibrotic areas with ablation lesions. The tagged ablation lesions should confirm encircling and/or covering of the entire contiguous fibrotic areas indicated by the mapping system. Ablation to the fibrotic areas should be performed as per the operator’s standard point lesion energy delivery strategy. It is suggested that a minimum of 8-10 s (and if available 10 g of force) lesions should be delivered. It is recommended that energy delivery (power and temperature) should be adjusted as needed when ablating within the posterior wall region over the region of the esophagus. The operator may connect 2 neighboring fibrotic areas or anchor fibrotic area to anatomic structure such as the isolated PV or valve annuli to avoid creating slow conduction zones or unanchored islands of fibrosis that might be deemed to be potentially arrhythmogenic. If the normal sinus rhythm cannot be restored after PVI and ablation of fibrotic areas followed by cardioversion in patients randomized to the fibrosis-guided ablation group (Group 2), the operator may to pursue further measures to eliminate recurrent arrhythmia, as described above for the conventional ablation group (Group 1).

Total duration of treatment in both arms will range from 1-2 hours.
Follow-up for both arms will be 18 months post treatment.
All investigators will attend an in-person training symposium for the intervention arm (Group 2)

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measures

The recurrence of atrial arrhythmia post-ablation, defined as a non-self-terminating bout of atrial fibrillation, atrial flutter, or atrial tachycardia demonstrated by at least two consecutive, valid ECG tracings occurring within 6 hours up to a maximum of 7 days of each other after the 90-day post-ablation blanking period.

The study outcome is formally defined by at least two consecutive, valid ECG tracings indicating an atrial arrhythmia (AA) (atrial fibrillation, atrial flutter or atrial tachycardia).

Secondary outcome measures

1. Measuring individual components of primary outcome (AF, AFl, AT), measured using ECG readings using either iPhone (daily recordings) or 12-lead ECG (baseline, 3 month, 12 and 18 month visit)
2. Symptomatic AA, measured using ECG readings using either iPhone (daily recordings) or 12-lead ECG (baseline, 3 month, 12 and 18 month post ablation) in conjunction with a 5-question survey about how the patient is feeling (symptoms of AA) answered weekly throughout the study
3. AF cycle length/regularity/termination, measured using 12-lead ECG at 3 month, 12 or 18 month post ablation)
4. CV-related hospitalization, measured using chart review and verbal medical history for each patient at baseline, 3 month, 12 and 18 months post ablation
5. CV related mortality, measured using chart review and verbal medical history for each patient at baseline, 3 month, 12 and 18 months post ablation
6. Quality of life, measured using the Toronto Atrial Fibrillation Severity Scale (AFSS) at 3, 12, and 18 months post ablation
7. AF burden, measured using the Toronto Atrial Fibrillation Severity Scale (AFSS) at 3, 12, and 18 months post ablation

Overall trial start date

01/04/2016

Overall trial end date

01/04/2019

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients with persistent AF defined as 7 days or more of AF as evidenced by either:
1.1 rhythm strip or
1.2. written documentation
2. Undergoing first AF ablation as per recent HRS consensus document (has not had a previous left atrial ablation or cardiac surgical procedure)
3. Age ≥ 18 years

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

900

Participant exclusion criteria

1. Contraindication for DE-MRI with a full dose of contrast agent
2. Contraindication to beta blockers, if necessary, for DE-MRI
3. Women currently pregnant
4. Mental or physical inability to take part in the study
5. Inability to be placed in MRI due to body mass or body habitus
6. Known terminally ill patients
7. Subjects without daily access to a smart phone or tablet compatible with the ECG Check application and ability to upload ECG tracings for the entire follow up period.

Recruitment start date

01/04/2016

Recruitment end date

01/04/2017

Locations

Countries of recruitment

Australia, Canada, China, France, Germany, Italy, Netherlands, Spain

Trial participating centre

Johns Hopkins University
Baltimore
Maryland
-
United States of America

Trial participating centre

Harvard University
Cambridge
Massachusetts
02138
United States of America

Trial participating centre

University of Pennsylvania
Philadelphia
Pennsylvania
19104
United States of America

Trial participating centre

Loyola University Chicago
1032 W Sheridan Rd
Illinois
60660
United States of America

Trial participating centre

University of South Florida
4202 E. Fowler Avenue Tampa
Florida
33620
United States of America

Trial participating centre

Leipzig University
Augustusplatz 10
Leipzig
04109
Germany

Trial participating centre

Klinikum Coburg
Ketschendorfer Str. 33
Coburg
96450
Germany

Trial participating centre

Kerckhoff-Klinik
Benekestraße 2-8
Bad Nauheim
61231
Germany

Trial participating centre

Bordeaux Segalen University
146 Rue Léo Saignat
Bordeaux
33000
France

Trial participating centre

University of Washington
Seattle
Washington
-
United States of America

Trial participating centre

Mayo Clinic
13400 E. Shea Blvd. Scottsdale
Arizona
85259
United States of America

Trial participating centre

Gregorio Marañón Hospital
Calle del Dr. Esquerdo, 46
Madrid
28007
Spain

Trial participating centre

Hospital Clínic de Barcelona
Villarroel, 170
Barcelona
08036
Spain

Trial participating centre

Haga Teaching Hospital
Hague
-
Netherlands

Trial participating centre

Mount Sinai Heart
One Gustave L. Levy Place New York
New York
10029-6574
United States of America

Trial participating centre

Ghent University
St. Pietersnieuwstraat 33
Gent
9000
Belgium

Trial participating centre

Swedish Medical Center
5300 Tallman Ave NW Seattle
Washington
98107
United States of America

Trial participating centre

University of Rostock
8051 Rostock
-
Germany

Trial participating centre

Brigham and Women's Hospital
75 Francis St Boston
Massachusetts
02115
United States of America

Trial participating centre

University Heart Center Freiburg (Universitäts-Herzzentrum Freiburg), Bad Krozingen
Südring 15
Bad Krozingen
79189
Germany

Trial participating centre

Cardiology Center Monzino (Centro Cardiologico Monzino)
Via S. Barnaba, 30
Milano
20122
Italy

Trial participating centre

University of Adelaide & Royal Adelaide Hospital
North Terrace, Adelaide
South Australia
5000
Australia

Trial participating centre

Hollywood Hospital
Monash Ave Nedlands
Western Australia
6009
Australia

Trial participating centre

Dresden University of Technology (Technischen Universität Dresden)
01069 Dresden
-
Germany

Trial participating centre

Isala Clinics (Isala Klinieken)
-
Netherlands

Trial participating centre

University of California, Los Angeles (UCLA)
Los Angeles
California
90095
United States of America

Trial participating centre

West China Hospital
37 Guoxue Alley Wuhou Chengdu
Sichuan
-
China

Trial participating centre

Beijing Anshen Hospital
Beijing
-
China

Trial participating centre

University of Sydney
New South Wales
2006
Australia

Trial participating centre

Provena St. Joseph Medical Center
333 Madison St Joliet
Illinois
60435
United States of America

Trial participating centre

Cleveland Clinic
2049 E 100th St Cleveland
Ohio
44195
United States of America

Trial participating centre

Valley Health System of NY and NJ
223 N Van Dien Ave Ridgewood
New Jersey
07450
United States of America

Sponsor information

Organisation

St. Jude Medical

Sponsor details

One St. Jude Medical Drive
St. Paul
55117
United States of America

Sponsor type

Industry

Website

Organisation

Siemens Medical Solutions USA, Inc.

Sponsor details

2501 N. Barrington Rd.
Hoffman Estates
60192
United States of America

Sponsor type

Industry

Website

Organisation

Medtronic Clinical Operations

Sponsor details

8200 Coral Sea Street NE
MVN 34
Mounds View
55112
United States of America

Sponsor type

Industry

Website

Organisation

St. Jude Medical

Sponsor details

3333 S. Diamond Canyon Road
Diamond Bar
91765
United States of America

Sponsor type

Industry

Website

Funders

Funder type

Not defined

Funder name

St. Jude Medical

Alternative name(s)

St. Jude Medical, Inc., SJM

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United States of America

Funder name

Siemens USA

Alternative name(s)

Siemens Corporation

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United States of America

Funder name

Medtronic

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United States of America

Results and Publications

Publication and dissemination plan

Manuscript writing will begin during the third and final year of the study. Results are estimated to be published one year after the study has been closed and the database has been locked, approximately April 2020. Results will be disseminated throughout the trial at national and international conferences such as the American Heart Association, American Cardiology Conference, and Heart Rhythm Society.

Intention to publish date

30/04/2020

Participant level data

Stored in repository

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

24/03/2016: Ethics approval information added.