Mitral ValvulopathyEPICAFNCT01649544
Comparison of Treatment of Atrial Fibrillation (AF) Between Surgical Ultrasonic Technology or Drug Therapy for Patients With AF Requiring Mitral Valve Surgery
A study testing EPICOR and Amiodarone in people with Mitral Valvulopathy and Atrial Fibrillation, run by Centre Hospitalier Universitaire de Saint Etienne at 5 sites in France.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mitral Valvulopathy, Atrial Fibrillation
- What is being tested?
- EPICOR and Amiodarone
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 5 sitesFrance
- Study dates
- Mar 2012to Sep 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- mitral valvulopathy requiring surgery
- paroxysmal atrial fibrillation or permanent or chronic atrial fibrillation
- Left atrium ≤ 55mm
- consent form signed
Who cannot join
- thyroid dysfunction
- pregnant
- contraindication of amiodarone
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
France5 sites
CHU de Grenoble
Grenoble
Hospices Civiles de Lyon
Lyon
CHU de Montpellier
Montpellier
CHU de Rennes
Rennes
CHU de Saint-Etienne
Saint-Etienne
About this study
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
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.
Read the 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.
- Conditions
- Mitral Valvulopathy, Atrial Fibrillation
- Being tested
- EPICOR, Amiodarone
- Keywords
- Mitral valvulopathy, Atrial Fibrillation, Amiodarone, Paroxysmal Atrial Fibrillation, Chronic Atrial Fibrillation, Ultrasound Technique
- Medical subject headings
- Heart Valve Diseases, Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EPICORDevice
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.
AmiodaroneDrug
| Study group | Role | What they receive |
|---|---|---|
| EPICOR | Experimental | 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) Receives: Device: EPICOR |
| Amiodarone | Active comparator | Cordarone :
400 mg/d during the 2 first months 200 mg/d from 3th to 18th month Receives: Drug: Amiodarone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Atrial Fibrillation episode
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
Measured: At 18 months
Secondary outcomes (4)
Adverse drug effects of Amiodarone
side effects attributable to treatment with amiodarone and has caused it to stop
Measured: At 18 months
major cardiovascular event
An atrial arrhythmia or heart failure or embolic events
Measured: At 18 months
Atrial tachycardia
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.
Measured: At 18 months
Death
Measured: At 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2012 (estimated)
- Study startMar 2012
- Primary completionSep 2015
- Study completionSep 2015
Why it stopped: End of commercialization of the medical device
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mitral ValvulopathyStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de Saint EtienneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, France
- Responsible party
- Sponsor
- Investigators
- Antoine DA COSTA, MD PhD, Principal investigator, CHU de Saint-Etienne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01649544
- Sponsor's protocol ID
- 1008058
- Other IDs
- 2011-A00275-36
- Acronym
- EPICAF
- Status last verified
- Nov 2015
- First submitted
- 23 Jul 2012
- Last updated
- 2 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01649544
- Acronym / sponsor ID
- EPICAF / 1008058
- Conditions
- Mitral Valvulopathy, Atrial Fibrillation
- Keywords
- Mitral valvulopathy, Atrial Fibrillation, Amiodarone, Paroxysmal Atrial Fibrillation, Chronic Atrial Fibrillation, Ultrasound Technique
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: End of commercialization of the medical device
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de Saint EtienneUniversity, hospital or other
- Collaborators
- Ministry of Health, France
- Study start
- Mar 2012
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 25 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| EPICOR | Experimental | Device: EPICORCardiac 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) |
| Amiodarone | Active comparator | Drug: AmiodaroneCordarone : 400 mg/d during the 2 first months 200 mg/d from 3th to 18th month |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- mitral valvulopathy requiring surgery
- paroxysmal atrial fibrillation or permanent or chronic atrial fibrillation
- Left atrium ≤ 55mm
- consent form signed
Key exclusion criteria (3 listed)
- thyroid dysfunction
- pregnant
- contraindication of amiodarone
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EPICORIntraoperatively, 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. | Device | EPICOR |
| Amiodarone | Drug | Amiodarone |
Primary outcome
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
4 secondary outcomes
Adverse drug effects of Amiodarone
Time frame: At 18 months
major cardiovascular event
Time frame: At 18 months
Atrial tachycardia
Time frame: At 18 months
Death
Time frame: At 18 months
Results and safety
The study was stopped early (reason given: End of commercialization of the medical device). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antoine DA COSTA, MD PhD principal investigator
CHU de Saint-Etienne
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing EPICOR and Amiodarone in people with Mitral Valvulopathy and Atrial Fibrillation, run by Centre Hospitalier Universitaire de Saint Etienne at 5 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: End of commercialization of the medical device). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Atrial Fibrillation episode (time frame: At 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2015.