Clinical trial NCT00736294: Prevention of Atrial Fibrillation by Inhibition Conversion Enzyme (ICE) After Radiofrequency Ablation of Atrial Flutter
Official title: Prevention of Atrial Fibrillation by the Prescription of Inhibition Conversion Enzyme (ICE) After Radiofrequency Ablation of Atrial Flutter
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Atrial Fibrillation
Atrial Flutter
Keywords: Catheter Ablation, Radiofrequency
Angiotensin-Converting Enzyme Inhibitors
Lead sponsor: Centre Hospitalier Universitaire de Saint Etienne
Sponsor class: OTHER
Collaborators: name: Sanofi
name: Ministry of Health, France
name: LivaNova
First posted: 2008-08-15
Enrollment: 198
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: At least one relevant symptomatic or asymptomatic atrial fibrillation event
timeFrame: From D1 to M12
Secondary outcomes:
measure: All relevant cardiovascular event
timeFrame: From D1 to M12
measure: Secondary effects of the treatment
timeFrame: From D1 to M12
Other outcomes:
Locations:
city: Brest
country: France
facility: CHU de Brest
city: Clermont Ferrand
country: France
facility: CHU de Clermont-Ferrand
city: Grenoble
country: France
facility: CHU de Grenoble
city: Montpellier
country: France
facility: CHU de Montpellier
city: Ollioules
country: France
facility: Polyclinique des Fleurs
city: Rennes
country: France
facility: CHU de Rennes
city: Rouen
country: France
facility: CHU de Rouen
city: Saint-etienne
country: France
facility: CHU de Saint-Etienne
Study officials:
affiliation: CHU de Saint-Etienne
name: Antoine DA COSTA, PhD MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Da Costa A, Thevenin 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, Barthelemy JC, Gouttard T, Isaaz K; Loire-Ardeche-Drome-Isere-Puy-de-Dome Trial of Atrial Flutter Investigators. Results from the Loire-Ardeche-Drome-Isere-Puy-de-Dome (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. doi: 10.1161/CIRCULATIONAHA.106.638395. Epub 2006 Oct 9.
citation: 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. doi: 10.1136/hrt.2003.033308. No abstract available.
citation: Madrid AH, Peng J, Zamora J, Marin I, Bernal E, Escobar C, Munos-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. doi: 10.1111/j.1540-8159.2004.00645.x.
citation: Heart Outcomes Prevention Evaluation Study Investigators; 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. N Engl J Med. 2000 Jan 20;342(3):145-53. doi: 10.1056/NEJM200001203420301.