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

Atrial Fibrillation Clinical Trial

— PREFACE  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00736294
• Other study ID #: 0608066
• Secondary ID: 2006-007032-10
• Status: Terminated
• Phase: Phase 3
• First received: August 14, 2008
• Last updated: July 27, 2015
• Start date: July 2008
• Est. completion date: March 2015

Study information

• Verified date: July 2015
• Source: Centre Hospitalier Universitaire de Saint Etienne
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)France: French Data Protection Authority
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 198
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atrial Fibrillation
• Atrial Flutter

Intervention

Drug:
• Ramipril
5 mg/d from D1 to M3 10 mg/d from M3 to M12 Tablets
• Placebo
5 mg/d from D1 to M3 10 mg/d from M3 to M12 Tablets

Locations

Country	Name	City	State
France	CHU de Brest	Brest
France	CHU de Clermont-Ferrand	Clermont Ferrand
France	CHU de Grenoble	Grenoble
France	CHU de Montpellier	Montpellier
France	Polyclinique des Fleurs	Ollioules
France	CHU de Rennes	Rennes
France	CHU de Rouen	Rouen
France	CHU de Saint-Etienne	Saint-etienne

Sponsors (4)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Saint Etienne	LivaNova, Ministry of Health, France, Sanofi

Country where clinical trial is conducted

France, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	At least one relevant symptomatic or asymptomatic atrial fibrillation event		From D1 to M12	No
Secondary	All relevant cardiovascular event		From D1 to M12	No
Secondary	Secondary effects of the treatment		From D1 to M12	Yes