CACAF-2: CACAF2 Study: Catheter Ablation for Cure of Atrial Fibrillation

• Sponsor: Biosense Webster EMEA (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00227344
• Collaborator: (none)
• Enrollment: 129
• Locations: 12
• Arms: 2
• Duration (Months): 53
• Patients Per Site: 10.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The objective of this prospective multicenter randomized study is to establish the effectiveness of treatment of persistent atrial fibrillation by encircling the pulmonary veins with radiofrequency (RF) ablation and creating additional lines of block with the aid of the NAVISTAR® THERMOCOOL® catheter in conjunction with the CARTO™ EP Navigation System. Effectiveness will be determined by comparing the chronic success of ablation therapy versus antiarrhythmic drug therapy, defined as the absence of persistent tachyarrhythmias during the first 24 months after a run-in phase of 2 months.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation	Device: RF ablation; Drug: Antiarrhythmic drugs	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 129 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Catheter Ablation for Cure of Atrial Fibrillation
• Study Start Date: Dec 1, 2004
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: May 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Catheter ablation	Device: RF ablation; Catheter ablation with NAVISTAR® THERMOCOOL® Catheter in conjunction with CARTO™ EP Navigation System
Active Comparator: 2 Antiarrhythmic drugs	Drug: Antiarrhythmic drugs; Best antiarrhythmic drug according to local practice (amiodarone suggested) throughout the study

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Absence of Persistent Atrial Tachyarrhythmias Relapse During the First 24 Months After the run-in Phase (2 Months). [within first 24 months after a 2-month run-in phase]

   Persistent atrial tachyarrhythmia is defined as lasting 7 or more days per two consecutive transtelephonic monitoring or electrocardiogram recordings (obtained at least one week apart) with no cardioversions.

Secondary Outcome Measures

1. Percentage of Participants With Total Absence of Any Documented Atrial Tachyarrhythmias Lasting Longer Than 30 Seconds During the First 24 Months After the run-in Phase (2 Months) [within first 24 months after a 2-month run-in phase]

2. Percentage of Procedural Success [The day of the procedure]

   Procedural success was determined on the day of the procedure (Day 0) and was based on responses to the following: "Has a validation of the lesions been performed by taking 3 points inside each circular lesion?" "If YES to #1, did you observe that none of them exceed 0.1 mV?" "Did you observe any adverse event during the procedure?" If the answers to (1 ) and (2 ) were YES and (3) was NO, then the procedure was determined a success.

3. Time to First Recurrence of Any Tachyarrhythmias Lasting 30 or More Seconds After the Run in Phase [day 61 through 790]

4. Percentage of Participants Achieving Clinical Success (Subjects Taking AADs That Remain Free From Any Tachyarrhythmias) in Association With Antiarrhythmic Drugs [at 26 months and at each patients last follow-up visit]

5. Quality of Life [at 14, 26 and 38 months]

6. Health-economics Parameters (Days of Hospitalization) [at 26 months and at each patients last follow-up visit]

7. Percentage of Participants With Normal Sinus Rhythm at the Last Follow-up Visit Measured by ECG and 24-hour Holter Monitor [at each patients last follow-up visit]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 18-70 years

• Written informed consent

• One documented relapse of atrial fibrillation (AF) during antiarrhythmic drug therapy after an electrical cardioversion

Exclusion Criteria:

• Permanent atrial fibrillation

• Patients who had tried >1 antiarrhythmic drug (Class I or Class III).

• AF was the sole rhythm for >6 months before the enrollment.

• Previous ablation for AF.

• AF is deemed secondary to a transient or correctable abnormality including electrolyte imbalance, trauma, recent surgery, infection, toxic ingestion, and endocrinopathy.

• Patients who have fibrillation episodes triggered by another uniform arrhythmia (eg, atrial flutter or atrial tachycardia).

• Patients with intra-atrial thrombus, tumor, or another abnormality that precludes catheter introduction.

• Patients with Wolf-Parkinson-White syndrome.

• Patients awaiting cardiac transplantation.

• Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-III-IV or ejection fraction (EF) <40%.

• Patients with unstable angina or acute myocardial infarction within 3 months.

• Patients with cardiac revascularization or other cardiac surgery within 6 months.

• Patients with heart disease in which corrective surgery is anticipated.

• Patients in whom appropriate vascular access is precluded.

• Pregnant women.

• A separate requirement for antiarrhythmic drug treatment, which will require an antiarrhythmic drug not previously tried for AF suppression.

• Prior atrial surgery.

• Contraindication to treatment with warfarin or other bleeding diathesis.

• Renal failure requiring dialysis.

• Hepatic failure.

• Participant in investigational clinical or device trial.

• Unwilling or unable to give informed consent.

• Inaccessible for follow-up.

• Psychological problem that might limit compliance.

• Active abuse of alcohol or other drugs which may be causative of AF.

• An implanted device (pacemaker or cardioverter-defibrillator).

• Left atrial diameter (anteroposterior) >50 mm.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Oulu Hospital	Oulu		Finland
2	Az. ULSS no. 15 Alta Padovana	Camposampiero (VE)		Italy
3	ASL no. 6	Cirie (TO)		Italy
4	Casa di Cura Villa Maria Cecilia	Cotignola		Italy
5	Az. Osp. di Ferrara- Arcispedale Sant'Anna	Ferrara		Italy
6	Ospedale Morgagni	Florence		Italy
7	Casa di Cura San Michele	Maddaloni		Italy
8	ULSS no. 13	Mirano (VE)		Italy
9	Ospedale San Eugenio	Rome		Italy
10	Az. Provinciale per I Serv. Sanit.	Trento		Italy
11	ULSS no. 10	Treviso (VE)		Italy
12	Heart hospital	London		United Kingdom

Sponsors and Collaborators

• Biosense Webster EMEA

Investigators

• Principal Investigator: Emanuele Bertaglia, MD, ULSS n.13, Mirano (VE), Italy
• Principal Investigator: Giuseppe Stabile, MD, Casa di Cura San Michele, Maddaloni, Italy

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Biosense Webster EMEA
• ClinicalTrials.gov Identifier: NCT00227344
• Other Study ID Numbers: CACAF2
• First Posted: Sep 28, 2005
• Last Update Posted: Apr 8, 2016
• Last Verified: Mar 1, 2016

• Additional relevant MeSH terms: Atrial Fibrillation; Anti-Arrhythmia Agents

Study Results

Participant Flow

Recruitment Details	One hundred twenty-nine (129) subjects were enrolled in the study at the time of termination. Ten of 13 study sites were in Italy, thus the majority of subjects were recruited from Italian sites. The sponsor's decision at study termination was to report primary and secondary endpoints for which meaningful data analysis was possible.

Arm/Group Title	Catheter Ablation	Antiarrhythmic Drug Treatment
Arm/Group Description	Catheter Ablation	Best antiarrhythmic drug according to local practice (amiodarone suggested) throughout the study
Period Title: Overall Study
STARTED	87	42
COMPLETED	75	37
NOT COMPLETED	12	5

Baseline Characteristics

Arm/Group Title	Catheter Ablation	Antiarrhythmic Drug Treatment	Total
Arm/Group Description	Catheter Ablation	Best antiarrhythmic drug according to local practice (amiodarone suggested) throughout the study	Total of all reporting groups
Overall Participants	87	42	129
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.3 (8.9)	64.3 (4.7)	59.6 (8.5)
Sex: Female, Male (Count of Participants)
Female	17 19.5%	21 50%	38 29.5%
Male	70 80.5%	21 50%	91 70.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Absence of Persistent Atrial Tachyarrhythmias Relapse During the First 24 Months After the run-in Phase (2 Months).
Description	Persistent atrial tachyarrhythmia is defined as lasting 7 or more days per two consecutive transtelephonic monitoring or electrocardiogram recordings (obtained at least one week apart) with no cardioversions.
Time Frame	within first 24 months after a 2-month run-in phase

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) analysis includes subjects with available transtelephonic monitoring data.

Arm/Group Title	Catheter Ablation	Antiarrhythmic Drug Treatment
Arm/Group Description	Catheter Ablation	Best antiarrhythmic drug according to local practice (amiodarone suggested) throughout the study
Measure Participants	75	37
Number [percentage of participants]	36.0 41.4%	45.9 109.3%

2. Secondary Outcome

Title	Percentage of Participants With Total Absence of Any Documented Atrial Tachyarrhythmias Lasting Longer Than 30 Seconds During the First 24 Months After the run-in Phase (2 Months)
Time Frame	within first 24 months after a 2-month run-in phase

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) analysis includes subjects with available transtelephonic monitoring data.

Arm/Group Title	Catheter Ablation	Antiarrhythmic Drug Treatment
Arm/Group Description	Catheter Ablation	Best antiarrhythmic drug according to local practice (amiodarone suggested) throughout the study
Measure Participants	75	37
Number [percentage of participants]	16.0 18.4%	24.3 57.9%

3. Secondary Outcome

Title	Percentage of Procedural Success
Description	Procedural success was determined on the day of the procedure (Day 0) and was based on responses to the following: "Has a validation of the lesions been performed by taking 3 points inside each circular lesion?" "If YES to #1, did you observe that none of them exceed 0.1 mV?" "Did you observe any adverse event during the procedure?" If the answers to (1 ) and (2 ) were YES and (3) was NO, then the procedure was determined a success.
Time Frame	The day of the procedure

Outcome Measure Data

Analysis Population Description

Procedural success was only calculated for the catheter ablation group. Intention to Treat (ITT) analysis of procedural success for the catheter ablation group was performed using available data. The "0" below the Antiarrhythmic Drug treatment group represents "not available."

Arm/Group Title	Catheter Ablation	Antiarrhythmic Drug Treatment
Arm/Group Description	Catheter Ablation	Best antiarrhythmic drug according to local practice (amiodarone suggested) throughout the study
Measure Participants	84	0
Number [percentage of participants]	70.2 80.7%

4. Secondary Outcome

Title	Time to First Recurrence of Any Tachyarrhythmias Lasting 30 or More Seconds After the Run in Phase
Time Frame	day 61 through 790

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) analysis includes subjects with available transtelephonic monitoring data. The upper bound of the confidence interval for the drug treatment group could not be calculated because of the high censoring rate. Therefore, "NA" is more appropriate in place of the maximum duration of follow-up (790.0) as the upper bound.

Arm/Group Title	Catheter Ablation	Antiarrhythmic Drug Treatment
Arm/Group Description	Catheter Ablation	Best antiarrhythmic drug according to local practice (amiodarone suggested) throughout the study
Measure Participants	75	36
Median (95% Confidence Interval) [days]	302.0	328.0

5. Secondary Outcome

Title	Percentage of Participants Achieving Clinical Success (Subjects Taking AADs That Remain Free From Any Tachyarrhythmias) in Association With Antiarrhythmic Drugs
Time Frame	at 26 months and at each patients last follow-up visit

Outcome Measure Data

Analysis Population Description

Study termination due to randomization imbalance. Data not analyzed since enrollment limited and therefore insufficient data to identify meaningful differences and draw significant conclusions. The "0" below represents "not available."

Arm/Group Title	Catheter Ablation	Antiarrhythmic Drug Treatment
Arm/Group Description	Catheter Ablation	Best antiarrhythmic drug according to local practice (amiodarone suggested) throughout the study
Measure Participants	0	0

6. Secondary Outcome

Title	Quality of Life
Time Frame	at 14, 26 and 38 months

Outcome Measure Data

Analysis Population Description

Study termination due to randomization imbalance. Data not analyzed since enrollment limited and therefore insufficient data to identify meaningful differences and draw significant conclusions. The "0" below represents "not available."

Arm/Group Title	Catheter Ablation	Antiarrhythmic Drug Treatment
Arm/Group Description	Catheter Ablation	Best antiarrhythmic drug according to local practice (amiodarone suggested) throughout the study
Measure Participants	0	0

7. Secondary Outcome

Title	Health-economics Parameters (Days of Hospitalization)
Time Frame	at 26 months and at each patients last follow-up visit

Outcome Measure Data

Analysis Population Description

Data not analyzed due to study termination - insufficient data to identify meaningful differences and draw significant conclusions.

Arm/Group Title	Catheter Ablation	Antiarrhythmic Drug Treatment
Arm/Group Description	Catheter Ablation	Best antiarrhythmic drug according to local practice (amiodarone suggested) throughout the study
Measure Participants	0	0

8. Secondary Outcome

Title	Percentage of Participants With Normal Sinus Rhythm at the Last Follow-up Visit Measured by ECG and 24-hour Holter Monitor
Time Frame	at each patients last follow-up visit

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT)analysis of sinus rhythm was performed for subjects with available Holter Monitor data.

Arm/Group Title	Catheter Ablation	Antiarrhythmic Drug Treatment
Arm/Group Description	Catheter Ablation	Best antiarrhythmic drug according to local practice (amiodarone suggested) throughout the study
Measure Participants	82	39
Number [percentage of participants]	75.6 86.9%	51.3 122.1%

Adverse Events

Arm/Group Title	Catheter Ablation		Antiarrhythmic Drug Treatment
Arm/Group Description	Catheter Ablation		Best antiarrhythmic drug according to local practice (amiodarone suggested) throughout the study
All Cause Mortality
	Catheter Ablation		Antiarrhythmic Drug Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Catheter Ablation		Antiarrhythmic Drug Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/87 (28.7%)		22/42 (52.4%)
Blood and lymphatic system disorders
anemia	0/87 (0%)	0	1/42 (2.4%)	1
low hemoglobin	0/87 (0%)	0	1/42 (2.4%)	1
lipotimia and hyperkaliemia	0/87 (0%)	0	1/42 (2.4%)	1
Cardiac disorders
coronary angiography	0/87 (0%)	0	1/42 (2.4%)	1
all types of atrial flutter including, but not limited to atypical and left atrial flutter	3/87 (3.4%)	3	1/42 (2.4%)	1
worsening ventricular function	0/87 (0%)	0	1/42 (2.4%)	1
sinusal arrest	0/87 (0%)	0	1/42 (2.4%)	1
bradycardia	0/87 (0%)	0	1/42 (2.4%)	1
torsade de pointes	0/87 (0%)	0	1/42 (2.4%)	1
heart failure	2/87 (2.3%)	2	1/42 (2.4%)	1
silent ischemic heart disease	0/87 (0%)	0	1/42 (2.4%)	1
sinus pause	2/87 (2.3%)	2	0/42 (0%)	0
dyspnea	2/87 (2.3%)	2	0/42 (0%)	0
myocardial infarction	1/87 (1.1%)	1	0/42 (0%)	0
Endocrine disorders
hyperthyroidism	0/87 (0%)	0	2/42 (4.8%)	2
diabetes	1/87 (1.1%)	1	0/42 (0%)	0
Eye disorders
reduced visual acuity secondary to cataract	0/87 (0%)	0	1/42 (2.4%)	1
Gastrointestinal disorders
colon polyp	1/87 (1.1%)	1	0/42 (0%)	0
General disorders
sudden death	0/87 (0%)	0	1/42 (2.4%)	1
Injury, poisoning and procedural complications
cardiac tamponade	2/87 (2.3%)	2	0/42 (0%)	0
inguinal hernia	2/87 (2.3%)	2	0/42 (0%)	0
cerebral aneurism	1/87 (1.1%)	1	0/42 (0%)	0
right knee trauma	1/87 (1.1%)	1	0/42 (0%)	0
brain injury secondary to facial trauma	1/87 (1.1%)	1	0/42 (0%)	0
artero-venious fistula	1/87 (1.1%)	1	0/42 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
lung cancer	0/87 (0%)	0	1/42 (2.4%)	1
increased tumor size	0/87 (0%)	0	1/42 (2.4%)	1
genital-urinary area neoplastic mass	1/87 (1.1%)	1	0/42 (0%)	0
Nervous system disorders
tremens	0/87 (0%)	0	1/42 (2.4%)	1
Renal and urinary disorders
renal failure	0/87 (0%)	0	1/42 (2.4%)	1
Respiratory, thoracic and mediastinal disorders
hemoptysis	0/87 (0%)	0	1/42 (2.4%)	1
nasal bleeding	1/87 (1.1%)	1	0/42 (0%)	0
Surgical and medical procedures
ablate and pace procedure	0/87 (0%)	0	1/42 (2.4%)	1
pacemaker implantation	1/87 (1.1%)	1	0/42 (0%)	0
atrioventricular node ablation	1/87 (1.1%)	1	0/42 (0%)	0
Vascular disorders
carotid atrery stenosis	0/87 (0%)	0	1/42 (2.4%)	1
transient ischemic attack	1/87 (1.1%)	1	0/42 (0%)	0
Other (Not Including Serious) Adverse Events
	Catheter Ablation		Antiarrhythmic Drug Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/87 (0%)		3/42 (7.1%)
Eye disorders
corneal deposit of amiodarone	0/87 (0%)	0	3/42 (7.1%)	3

Limitations/Caveats

The study was terminated early due to randomization imbalance. The relatively small number of subjects enrolled limited the amount of data available for analysis. Because the study did not reach its targeted enrollment, the study is underpowered.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between the Principal Investigator (PI)/Institution and the Sponsor (or its agents) that restricts the PI's rights to discuss, present or publish trial results after the trial is completed. Please contact Biosense Webster, Inc. for additional information.