Prevention of Atrial Fibrillation by Inhibition Conversion Enzyme (ICE) After Radiofrequency Ablation of Atrial Flutter

Condition(s) targeted: Atrial Fibrillation; Atrial Flutter

Intervention: Ramipril (Drug); Placebo (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Centre Hospitalier Universitaire de Saint Etienne

Official(s) and/or principal investigator(s):
Antoine DA COSTA, PhD MD, Principal Investigator, Affiliation: CHU de Saint-Etienne

Overall contact:
Antoine DA COSTA, PhD MD, Phone: +33 (0) 4 77 82 83 40, Email: antoine.dacosta@chu-st-etienne.fr

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.

Official title: Prevention of Atrial Fibrillation by the Prescription of Inhibition Conversion Enzyme (ICE) After Radiofrequency Ablation of Atrial Flutter

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: At least one relevant symptomatic or asymptomatic atrial fibrillation event

Secondary outcome:

All relevant cardiovascular event

Secondary effects of the treatment

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- first atrial flutter, or recurrence of atrial flutter

- age > 18 years old

- 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

Antoine DA COSTA, PhD MD, Phone: +33 (0) 4 77 82 83 40, Email: antoine.dacosta@chu-st-etienne.fr

CHU de Saint-Etienne, SAINT-ETIENNE 42 055, France; Recruiting
Antoine DA COSTA, MD PhD, Principal Investigator
Cécile ROMEYER-BOUCHARD, MD, Sub-Investigator

CHU de Rouen, ROUEN 76031, France; Not yet recruiting
Frédéric ANSELME, MD PhD, Principal Investigator
Arnaud SAVOURE, MD, Sub-Investigator

CHU de Grenoble, GRENOBLE 38043, France; Not yet recruiting
Pascal DEFAYE, MD, Principal Investigator
Peggy JACON, MD, Sub-Investigator

CHU de Clermont-Ferrand, CLERMONT FERRAND 63003, France; Not yet recruiting
Hassan MANSOUR, MD, Principal Investigator
Yannick SALUDAS, MD, Sub-Investigator
Jean PONSONNAILLE, MD PhD, Sub-Investigator

CHU de Montpellier, MONTPELLIER 34295, France; Not yet recruiting
Jean-Luc PASQUIER, MD, Principal Investigator
Franck RACZKA, MD, Sub-Investigator

CHU de Rennes, RENNES 35033, France; Not yet recruiting
Dominique PAVIN, MD, Principal Investigator
Philippe MABO, MD PhD, Sub-Investigator

CHU de Brest, BREST 29609, France; Not yet recruiting
Marjaneh FATEMI, MD, Principal Investigator
Jacques MANSOURATI, MD PhD, Sub-Investigator

Polyclinique des Fleurs, OLLIOULES 83190, France; Not yet recruiting
Thierry CHALVIDAN, MD, Principal Investigator
Olivier ROUX, MD, Sub-Investigator

Related 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.

Starting date: July 2008
Ending date: December 2012
Last updated: August 19, 2008