Plain English Summary
Background and study aims
Atrial fibrillation (AF) is a common heart condition, affecting millions of people worldwide. The heart consists of two upper chambers (atria) and two lower chambers (ventricles). Inside the right atrium, a cluster of cells (sinus node) are responsible for firing electrical signals into the heart muscle causing the heart to beat regularly (sinus rhythm). When a person is suffering from AF, the normal signals from the sinus node do not work properly, causing other parts of the atria to fire chaotically. These uncoordinated signals cause the heart to beat irregularly and often very fast (arrhythmia). A common starting point for treating AF is the use of antiarrhythmic drugs. There are several types of antiarrhythmics, however they generally work on the nervous system to prevent abnormal firing of electrical signals. Although these medications are widely used, some people do not respond to treatment. Catheter ablation is a surgical technique which is used to destroy the areas of the heart which are sending out the irregular signals. In the procedure, a thin flexible tube (catheter) is inserted into the groin and guided up to the heart. The tip of the catheter then either burns (radiofrequency ablation) or freezes (cryoablation) the affected areas. This procedure is often very successful, and can completely cure AF in some cases. The aim of this study is to find out whether using catheter ablation at the same time as antiarrhythmic drugs is better at improving sinus rhythm than antiarrhythmic drugs alone.
Who can participate?
Adults with a history of AF who are intolerant to antiarrhythmic drugs or treatment with antiarrhythmic drugs has failed.
What does the study involve?
Participants are randomly allocated to one of two groups. The first group receive a combination of antiarrhythmic drugs and a catheter ablation procedure. The second group receive antiarrhythmic drugs only. All participants are asked to wear an ECG recorder (a device which monitors how well the heart is beating and if there are any irregularities) for three months, which send information to the research team every day. Participants in both groups are also have regular ECG scans over a period of 144 months to find out whether their sinus rhythm has improved and to monitor how many participants in each group survive all together.
What are the possible benefits and risks of participating?
A potential benefit is that patients who receive catheter ablation may show an improvement to their sinus rhythm and may have a better chance of survival. Risks of participating include the general risks associated with antiarrhythmic drugs, as well as a low risk of complications in the catheter ablation group from the procedure.
Where is the study run from?
Casa di Cura San Michele (lead centre) and 3 other hospitals in Italy
When is the study starting and how long is it expected to run for?
February 2002 to May 2015
Who is funding the study?
Casa di Cura San Michele (Italy)
Who is the main contact?
Dr Emanuele Bertaglia
Trial website
Contact information
Type
Scientific
Primary contact
Dr Emanuele Bertaglia
ORCID ID
http://orcid.org/0000-0002-3878-2904
Contact details
via Ca' Rossa
35
Venice
30173
Italy
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
NA
Study information
Scientific title
Catheter ablation treatment in patients with drug-refractory atrial fibrillation: A prospective,
multi-centre, randomized, controlled study
Acronym
CACAF
Study hypothesis
Concurrent catheter ablation and antiarrhythmic drugs improve maintenance of sinus rhythm in comparison to antiarrhythmic drugs alone in patients with paroxysmal and persistent atrial fibrillation.
Ethics approval
San Michele Clinic - Maddaloni (CE) Italy, 07/12/2001, ref: PROT. 22001/CE
Study design
Prospective multi-centre randomised parallel trial
Primary study design
Interventional
Secondary study design
Randomised parallel trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Atrial fibrillation
Intervention
Participants are randomly allocated into two treatment groups:
Group 1: Participants in the first group are given antiaarhythmic drugs + catheter ablation (pulmonary vein ablation, right isthmus ablation, left isthmus ablation).
Group 2: Participants in the first group are given antiaarhythmic drugs (preferably amiodarone) only.
In both arms, treatment with antiarrhytmic drugs lasted for the whole follow-up. Patients were followed up by means of a trans-telephonic ECG recorder (Sorin Life Watch, Italy), with data being transmitted daily for 3 months, and by means of standard ECG, Holter monitoring at 1, 4, 7, 10, and 13 months. Thereafter, patients were followed up according to local practice, and between 1st June 2014 and 31st May 2015 they underwent an in-office examination or a phone interview, and repeated a 12-lead ECG.
Intervention type
Mixed
Phase
Drug names
Primary outcome measure
Maintenance of sinus rhythm at follow-up, measured with transtelephonic ECG for the first 3 months, with 24 hour Holter monitoring for the first 12 months, and with 12-lead ECG for 144 months.
Secondary outcome measures
Cumulative survival, measured as whether a patient is alive at 144 months follow-up (+/- 3 months).
Overall trial start date
01/02/2002
Overall trial end date
31/05/2015
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Aged between 18 and 80 years
2. History of paroxysmal (1 or more episodes of AF a month in the last 12 months, each lasting more than 60 min but less than 7 days, with all episodes terminating spontaneously) or persistent (2 or more episodes of AF in the last 12 months , each lasting more than 7 days before being terminated medically) atrial fibrillation first diagnosed at least 6 months before enrollment
3. Intolerant of antiarrhythmic drugs or in whom 2 or more antiarrhythmic drug regimens had failed
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
137
Participant exclusion criteria
1. Permanent atrial fibrillation (atrial fibrillation was the sole rhythm for the last 12 months)
2. Atrial fibrillation secondary to a transient or correctable abnormality, including electrolyte imbalance, trauma, recent surgery, infection, toxic ingestion, and endocrinopathy
3. Persistence of atrial fibrillation episodes triggered by another uniform arrhythmia (i.e. atrial flutter or atrial tachycardia) despite previous supraventricular tachycardia ablation
4. Intra-atrial thrombus, tumour, or other abnormality precluding catheter insertion
5. Wolff–Parkinson–White syndrome
6. Heart failure with NYHA class III or IV or left ventricular ejection fraction <35%
7. Unstable angina or acute myocardial infarction within 3 months
8. Cardiac revascularization or other cardiac surgery within 6 months or with prior atrial surgery
9. Renal failure requiring dialysis, or hepatic failure
10. An implanted device (pacemaker or cardioverter-defibrillator)
11. Left atrial diameter >60 mm
Recruitment start date
01/02/2002
Recruitment end date
30/06/2003
Locations
Countries of recruitment
Italy
Trial participating centre
Casa di Cura San Michele
Via Montella, 16
Maddaloni (CE)
81024
Italy
Trial participating centre
Ospedale Civile
Via XXIX Aprile, 2
Mirano (VE)
30035
Italy
Trial participating centre
Ospedale Civile
Via Battitore, 7/9
Ciriè (TO)
10073
Italy
Sponsor information
Organisation
Casa di Cura San Michele
Sponsor details
via Montella
16
Maddaloni
81024
Italy
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Hospital/treatment centre
Funder name
Casa di Cura San Michele
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in The Journal of the American Medical Association.
Intention to publish date
31/12/2015
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list
2016 results in https://www.ncbi.nlm.nih.gov/pubmed/27989681