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Prevention of Atrial Fibrillation by Inhibition Conversion Enzyme (ICE) After Radiofrequency Ablation of Atrial Flutter (PREFACE)
This study is currently recruiting participants.
Verified by Centre Hospitalier Universitaire de Saint Etienne, January 2010
First Received: August 14, 2008   Last Updated: January 5, 2010   History of Changes
Sponsor: Centre Hospitalier Universitaire de Saint Etienne
Collaborators: Sanofi-Aventis
Ministry of Health, France
Sorin Group
Information provided by: Centre Hospitalier Universitaire de Saint Etienne
ClinicalTrials.gov Identifier: NCT00736294
  Purpose

Atrial Flutter [AFL] is a relatively frequent arrhythmia, considered as benign, but associated with both invalidating symptoms and thromboembolic risk. The objective of the treatment consists to on the one hand the sinus rhythm [SR] restoration and on the other hand the prevention of the long-term recurrence. In this clinical setting, AFL radiofrequency ablation [RFA] became the first line therapy due to its both high effectiveness and safety. The effectiveness of AFL RFA is attenuated by the subsequent risk of atrial fibrillation [AFib] close to 25% at 1 year. This risk of subsequent AFib is related to the common substrate between both arrhythmias.

When AFib occurs, the interest to maintain the SR is still required, even if recent studies did not show a significant difference in term of total mortality between rate or rhythm control strategies [AFFIRM, RACE and PIAF studies]. The studies published underlined the anti-arrhythmic drugs limits in patients with both arrhythmias [AFib and AFL]. After years centered on the mechanisms and the electric treatments of AFib, researchers are nowadays focusing on the study's evaluation of the atrial tissue substrate.

Accordingly, the renin-angiotensin system role was investigated in many works. Indeed, angiotensin II plays a role in the modification of atrial pressure and in the fibers stretching ["stretch"], conditions required for the development of AFib. Angiotensin II is also a factor implied in the tissue fibrosis leading to tissue proliferation and collagen alteration. These mechanisms lead to atria cells conduction disorders and refractory periods modification. Moreover, the enzyme of conversion expression and the angiotensin II receptors deterioration were observed in patients with AFib.

This brings to the concept of AFib treatment while interfering on tissue remodeling by the way of renin-angiotensin system. Drugs such as the angiotensin converting enzyme inhibition [ACEI] may reduce AFib in patients with heart failure. No randomized study so far has compared the ACEI drugs against placebo among high-risk patients of AFib in post AFL RFA area. On the basis of experimental and clinical study, the investigators seek to evaluate the ACEI use in the prevention of AFib in an AFL post RFA ablation.


Condition Intervention Phase
Atrial Fibrillation
Atrial Flutter
Drug: Ramipril
Drug: Placebo
Phase III

Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Official Title: Prevention of Atrial Fibrillation by the Prescription of Inhibition Conversion Enzyme (ICE) After Radiofrequency Ablation of Atrial Flutter

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire de Saint Etienne:

Primary Outcome Measures:
  • At least one relevant symptomatic or asymptomatic atrial fibrillation event [ Time Frame: From D1 to M12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • All relevant cardiovascular event [ Time Frame: From D1 to M12 ] [ Designated as safety issue: No ]
  • Secondary effects of the treatment [ Time Frame: From D1 to M12 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 390
Study Start Date: July 2008
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
Inhibition Conversion Enzyme
Drug: Ramipril
5 mg/d from D1 to M3 10 mg/d from M3 to M12 Tablets
2: Placebo Comparator
Placebo
Drug: Placebo
5 mg/d from D1 to M3 10 mg/d from M3 to M12 Tablets

Detailed Description:

The main goal of this study is to compare within 12 months, the effectiveness of an ACEI [Ramipril] versus placebo on the prevention of AFib after AFL RFA.

This study is a randomized, prospective, double blind, multicenter study comparing ramipril vs. placebo in 2 parallel groups.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • first atrial flutter, or recurrence of atrial flutter
  • affiliated or a beneficiary of a social security category
  • treated by radiofrequency ablation (< 72 h)
  • having signed the inform consent form

Exclusion Criteria:

  • contra-indication to right catheterism
  • contra-indication to angiotensin converting enzym inhibitors
  • contra-indication to anticoagulation treatment
  • having already a angiotensin converting enzym inhibitor treatment
  • recent (< 3 months) hearth failure with left ventricular ejection fraction < 45%
  • pregnant women or breast-feeding
  • severe renal disease
  • serum potassium > 5 mmol/l
  • requiring a antiarrythmic treatment
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00736294

Contacts
Contact: Antoine DA COSTA, PhD MD +33 (0) 4 77 82 83 40 antoine.dacosta@chu-st-etienne.fr
Contact: Juanita TECHER, CRA +33 (0) 4 77 12 76 55 juanita.techer@chu-st-etienne.fr

Locations
France
CHU de Saint-Etienne Recruiting
Saint-etienne, France, 42 055
Principal Investigator: Antoine DA COSTA, MD PhD            
Sub-Investigator: Cécile ROMEYER-BOUCHARD, MD            
CHU de Rouen Recruiting
Rouen, France, 76031
Principal Investigator: Frédéric ANSELME, MD PhD            
Sub-Investigator: Arnaud SAVOURE, MD            
Sub-Investigator: Anne-Françoise CAILLEUX, MD            
CHU de Grenoble Recruiting
Grenoble, France, 38043
Principal Investigator: Pascal DEFAYE, MD            
Sub-Investigator: Peggy JACON, MD            
CHU de Clermont-Ferrand Recruiting
Clermont Ferrand, France, 63003
Principal Investigator: Hassan MANSOUR, MD            
Sub-Investigator: Yannick SALUDAS, MD            
Sub-Investigator: Jean PONSONNAILLE, MD PhD            
Polyclinique des Fleurs Not yet recruiting
Ollioules, France, 83190
Principal Investigator: Thierry CHALVIDAN, MD            
Sub-Investigator: Olivier ROUX, MD            
CHU de Rennes Recruiting
Rennes, France, 35033
Principal Investigator: Dominique PAVIN, MD            
Sub-Investigator: Philippe MABO, MD PhD            
Sub-Investigator: Claude DAUBERT, MD            
Sub-Investigator: Aude SOLNON, MD            
Sub-Investigator: Christophe LECLERCQ, MD            
CHU de Brest Recruiting
Brest, France, 29609
Principal Investigator: Marjaneh FATEMI, MD            
Sub-Investigator: Jacques MANSOURATI, MD PhD            
CHU de Montpellier Recruiting
Montpellier, France, 34295
Principal Investigator: Jean-Luc PASQUIER, MD            
Sub-Investigator: Franck RACZKA, MD            
Sponsors and Collaborators
Centre Hospitalier Universitaire de Saint Etienne
Sanofi-Aventis
Ministry of Health, France
Sorin Group
Investigators
Principal Investigator: Antoine DA COSTA, PhD MD CHU de Saint-Etienne
  More Information

Publications:
Da Costa A, Thévenin J, Roche F, Romeyer-Bouchard C, Abdellaoui L, Messier M, Denis L, Faure E, Gonthier R, Kruszynski G, Pages JM, Bonijoly S, Lamaison D, Defaye P, Barthélemy JC, Gouttard T, Isaaz K; Loire-Ardèche-Drôme-Isère-Puy-de-Dôme Trial of Atrial Flutter Investigators. Results from the Loire-Ardèche-Drôme-Isère-Puy-de-Dôme (LADIP) trial on atrial flutter, a multicentric prospective randomized study comparing amiodarone and radiofrequency ablation after the first episode of symptomatic atrial flutter. Circulation. 2006 Oct 17;114(16):1676-81. Epub 2006 Oct 9.
Da Costa A, Romeyer-Bouchard C, Zarqane-Sliman N, Messier M, Samuel B, Kihel A, Faure E, Isaaz K. Impact of first line radiofrequency ablation in patients with lone atrial flutter on the long term risk of subsequent atrial fibrillation. Heart. 2005 Jan;91(1):97-8. No abstract available.
Madrid AH, Peng J, Zamora J, Marín I, Bernal E, Escobar C, Muños-Tinoco C, Rebollo JM, Moro C. The role of angiotensin receptor blockers and/or angiotensin converting enzyme inhibitors in the prevention of atrial fibrillation in patients with cardiovascular diseases: meta-analysis of randomized controlled clinical trials. Pacing Clin Electrophysiol. 2004 Oct;27(10):1405-10.
Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000 Jan 20;342(3):145-53. Erratum in: 2000 May 4;342(18):1376. N Engl J Med 2000 Mar 9;342(10):748.

Responsible Party: Centre Hospitalier Universitaire de Saint Etienne ( Clément CAILLAUX )
Study ID Numbers: 0608066, 2006-007032-10
Study First Received: August 14, 2008
Last Updated: January 5, 2010
ClinicalTrials.gov Identifier: NCT00736294     History of Changes
Health Authority: France: Afssaps - French Health Products Safety Agency;   France: French Data Protection Authority

Keywords provided by Centre Hospitalier Universitaire de Saint Etienne:
Catheter Ablation, Radiofrequency
Angiotensin-Converting Enzyme Inhibitors

Additional relevant MeSH terms:
Pathologic Processes
Heart Diseases
Molecular Mechanisms of Pharmacological Action
Angiotensin-Converting Enzyme Inhibitors
Enzyme Inhibitors
Cardiovascular Diseases
Atrial Fibrillation
Pharmacologic Actions
Atrial Flutter
Protease Inhibitors
Arrhythmias, Cardiac

ClinicalTrials.gov processed this record on February 08, 2010