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

NCT ID: NCT00736294

Last Updated: 2015-07-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

198 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-07-31

Study Completion Date

2015-03-31

Brief Summary

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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

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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.

Conditions

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Atrial Fibrillation Atrial Flutter

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Ramipril

Inhibition Conversion Enzyme

Group Type EXPERIMENTAL

Ramipril

Intervention Type DRUG

5 mg/d from D1 to M3 10 mg/d from M3 to M12 Tablets

Placebo

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

5 mg/d from D1 to M3 10 mg/d from M3 to M12 Tablets

Interventions

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Ramipril

5 mg/d from D1 to M3 10 mg/d from M3 to M12 Tablets

Intervention Type DRUG

Placebo

5 mg/d from D1 to M3 10 mg/d from M3 to M12 Tablets

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sanofi

INDUSTRY

Sponsor Role collaborator

Ministry of Health, France

OTHER_GOV

Sponsor Role collaborator

LivaNova

INDUSTRY

Sponsor Role collaborator

Centre Hospitalier Universitaire de Saint Etienne

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Antoine DA COSTA, PhD MD

Role: PRINCIPAL_INVESTIGATOR

CHU de Saint-Etienne

Locations

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CHU de Brest

Brest, , France

Site Status

CHU de Clermont-Ferrand

Clermont-Ferrand, , France

Site Status

CHU de Grenoble

Grenoble, , France

Site Status

CHU de Montpellier

Montpellier, , France

Site Status

Polyclinique des Fleurs

Ollioules, , France

Site Status

CHU de Rennes

Rennes, , France

Site Status

CHU de Rouen

Rouen, , France

Site Status

CHU de Saint-Etienne

Saint-Etienne, , France

Site Status

Countries

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France

References

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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.

Reference Type BACKGROUND
PMID: 17030680 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15604348 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15511250 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10639539 (View on PubMed)

Other Identifiers

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2006-007032-10

Identifier Type: OTHER

Identifier Source: secondary_id

0608066

Identifier Type: -

Identifier Source: org_study_id

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