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Comparison of Treatment of Atrial Fibrillation (AF) Between Surgical Ultrasonic Technology or Drug Therapy for Patients With AF Requiring Mitral Valve Surgery (EPICAF)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01649544
Recruitment Status : Terminated (End of commercialization of the medical device)
First Posted : July 25, 2012
Last Update Posted : December 2, 2015
Ministry of Health, France
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Saint Etienne

Brief Summary:

In pre-operative cardiac surgery, 30 to 40% of patients with mitral valvulopathy have had episodes of paroxysmal atrial fibrillation (PAF) or are in permanent or chronic atrial fibrillation (CAF). According to the 1999 PMSI data, close to 4000 mitral valve interventions were performed in France, in other words, more than 1000 patients present with this condition annually; despite a surgical correction of their valvulopathy, patients presenting with a pre-operative chronic atrial fibrillation remain in fibrillation following surgery despite treatment with anti-arrhythmic agents associated or not with a cardioversion. Thus, the survival rate without AF recurrence is 10% at 1 year and 5% at 2 years in patients with AF prior to surgery; on the other hand, patients in sinus rhythm at the time of surgery and without an antecedent of AF exhibit an incidence of no AF of 90% and 74% at 1 and 2 years, respectively. It has also been shown in numerous studies that the long-term morbidity in patients with atrial valve surgery is higher in those with AF.

For more than 10 years, radio-frequency techniques using the endocavitary approach have shown a greater efficacy in maintaining sinus rhythm than drug therapy even though the techniques are invasive. These radio-frequency techniques were developed and tested during mitral surgery, but, to the investigators knowledge, there is only one randomized study that was carried out in a population with permanent AF using radio-frequency technique via the endocardial approach. Maintenance of sinus rhythm was obtained in only 44.4% of patients versus 4.5% in the control group; these results are not in accordance with the published prospective and retrospective registries using the technique peri-operatively. The principal problem of this study is the absence of medical treatment in the control group. In addition, the use of the radio-frequency technique requires an atriotomy resulting in a prolonged surgical time, which increases the peri-operative morbidity.

Other simpler ablation techniques have been developed, such as the one using ultrasound. In comparison with the radio-frequency method, this latter technique presents numerous advantages including the absence of an atriotomy due to the fact that the epicardial pathway is used, a short procedure time (11 min on average), excellent reproducibility, the transmural character of the lesions, along with the simplicity of application. There is not, to the investigators knowledge, a randomized study comparing the peri-operative ultrasound technique (EPICOR) in mitral valve surgery with the conservative reference treatment, notably mitral valve surgery coupled with long-term amiodarone treatment. In effect, while amiodarone is the most efficacious anti-arrhythmic agent in the long-term, this drug is associated with a high percentage of significant side effects, close to 20% at 2 years. The only available results using the ultrasound technique are the registries pertaining to the follow-up of patients undergoing cardiac mitral or aortic surgery, with an antecedent of AF. The results appear to be encouraging with 85% of cases maintained in sinus rhythm at 12 months in the most recent studies. In this clinical context, a French multi-centric registry evaluated the peri-operative treatment of AF with all of the proposed techniques (cryotherapy, radio-frequency, and ultrasound). The percentage of maintenance of sinus rhythm appears to be lower than in the historical registries, at the level of 60%, but the techniques used in this registry were multiple even if 50% of patients were treated with ultrasound; in addition, there was no randomization and follow-up was only for 6 months.

Condition or disease Intervention/treatment Phase
Mitral Valvulopathy Atrial Fibrillation Device: EPICOR Drug: Amiodarone Not Applicable

Detailed Description:
As a consequence, it is very difficult to have a precise idea, in the literature, of the medium- and long-term efficacy of this technique. Despite a diffusion and utilization of the technique in clinical practice, the efficacy of the ultrasound technique has not been compared, in a standardized manner, with amiodarone, which is the only anti-arrhythmic agent that has shown good efficacy in maintaining post-operative sinus rhythm following cardiac surgery. We propose to undertake an open, prospective, randomized, multicenter study evaluating the efficacy of treatment with ultrasound (EPICOR) in the maintenance of sinus rhythm following mitral surgery in two parallel groups, one group with ablation via ultrasound "EPICOR" and a control group treated with "amiodarone", including a long-term follow-up of 18 months. The strategy in this study necessitates the use of amiodarone in the two groups during the first 2 months followed by a cardioversion in the cases of persistent AF 2 months following surgery in both groups, with a cessation of amiodarone therapy in the ultrasound group and maintenance of therapy in the control group. The parallel treatment with amiodarone in the two groups following the surgical intervention is necessary in order to avoid confounding factors in the analysis. In effect, AF during the postoperative period is frequent and may be considered to be secondary to a number of factors, such as the surgery itself, inflammation, temperature, metabolic disturbances, pericardial effusion, etc. This approach is justified, because if the benefit associated with the peri-operative ultrasound technique is validated, this would allow for a reduction in the use of anti-arrhythmic agents, which are associated with side effects, along with a decrease in long-term morbidity via the resulting maintenance of sinus rhythm. In addition, the technique of ablation via ultrasound could, among others, replace the surgical technique of reference (Cox surgery) for which the principal inconvenience is the prolongation of the time of surgery, resulting in an elevated peri-operative morbidity. Therefore, the principal objective of the study is to compare, at 18 months, the efficacy of surgical treatment with ultrasound (EPICOR) on the maintenance of sinus rhythm following mitral valve surgery in comparison with amiodarone.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Comparison of Treatment of Atrial Fibrillation (AF) Between Surgical Ultrasonic Technology (EPICOR) or Drug Therapy (Cordarone) for Patients With AF Requiring Mitral Valve Surgery
Study Start Date : March 2012
Actual Primary Completion Date : September 2015
Actual Study Completion Date : September 2015

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: EPICOR

Cardiac ablation system EPICOR (CE n°0344).

  • ablation device EpicorTM UltraCinchTM LP (Class III device)
  • Positioning system and calibration EpicorTM LP (LP PASTM; device Class IIa)
  • Cable connection EpicorTM LP (unsterile)
  • Ablation Control System EpicorTM LP (Class IIb)
Device: EPICOR
Intraoperatively, in addition to the usual gesture, it will be conducted a systematic exclusion-ligation of the left atrium and the establishment of electrodes atrial and ventricular pacing. The right pulmonary veins are isolated by dissection of the inter-atrial groove and application of the probe by biting on the atrial tissue, the procedure is identical on the left after dissection of the area between the left pulmonary artery and pulmonary veins. The use of ultrasound application will require 10 minutes to around the pulmonary veins using a multi-electrode probe set to deliver an output pulse from 15 to 100 Watts at a frequency from 3.5 to 4.6 MHz. Using EPICOR extends the operating time of 15 minutes.

Active Comparator: Amiodarone

Cordarone :

400 mg/d during the 2 first months 200 mg/d from 3th to 18th month

Drug: Amiodarone

Primary Outcome Measures :
  1. Atrial Fibrillation episode [ Time Frame: At 18 months ]
    At least one episode of symptomatic AF or asymptomatic sustained [> 10 minutes] documented by an ECG or an R-test changes, occurring between 3 months (after restoration of sinus rhythm by cardioversion if necessary at the end of the 2nd month) and 18th month

Secondary Outcome Measures :
  1. Adverse drug effects of Amiodarone [ Time Frame: At 18 months ]
    side effects attributable to treatment with amiodarone and has caused it to stop

  2. major cardiovascular event [ Time Frame: At 18 months ]
    An atrial arrhythmia or heart failure or embolic events

  3. Atrial tachycardia [ Time Frame: At 18 months ]
    Atrial tachycardia whose frequency is between 150 and 250 per minute and shows the appearance of which electrocardiographic waves P positive on D2, D3 and AVF.

  4. Death [ Time Frame: At 18 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • mitral valvulopathy requiring surgery
  • paroxysmal atrial fibrillation or permanent or chronic atrial fibrillation
  • Left atrium ≤ 55mm
  • consent form signed

Exclusion Criteria:

  • thyroid dysfunction
  • pregnant
  • contraindication of amiodarone

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01649544

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CHU de Grenoble
Grenoble, France
Hospices Civiles de Lyon
Lyon, France
CHU de Montpellier
Montpellier, France
CHU de Rennes
Rennes, France
CHU de Saint-Etienne
Saint-etienne, France
Sponsors and Collaborators
Centre Hospitalier Universitaire de Saint Etienne
Ministry of Health, France
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Principal Investigator: Antoine DA COSTA, MD PhD CHU de Saint-Etienne

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Responsible Party: Centre Hospitalier Universitaire de Saint Etienne Identifier: NCT01649544     History of Changes
Other Study ID Numbers: 1008058
2011-A00275-36 ( Other Identifier: ANSM )
First Posted: July 25, 2012    Key Record Dates
Last Update Posted: December 2, 2015
Last Verified: November 2015
Keywords provided by Centre Hospitalier Universitaire de Saint Etienne:
Mitral valvulopathy
Atrial Fibrillation
Paroxysmal Atrial Fibrillation
Chronic Atrial Fibrillation
Ultrasound Technique
Additional relevant MeSH terms:
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Atrial Fibrillation
Heart Valve Diseases
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Anti-Arrhythmia Agents
Vasodilator Agents
Potassium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Sodium Channel Blockers
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 CYP3A Inhibitors