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

Phase 3

Terminated

• Conditions: Atrial Fibrillation; Atrial Flutter
• Interventions: Drug: Ramipril; Drug: Placebo

• Registration Number: NCT00736294
• Lead Sponsor: Centre Hospitalier Universitaire de Saint Etienne

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.

Study Timeline

• Study Start: 2008-07
• Study First Submitted: 2008-08-14
• Study First Submitted QC: 2008-08-14
• Study First Posted: 2008-08-15
• Primary Completion: 2015-03
• Study Completion: 2015-03
• Status Verified: 2015-07
• Last Update Submitted: 2015-07-27
• Last Update Posted: 2015-07-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 198

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ramipril	Ramipril	Inhibition Conversion Enzyme
Placebo	Placebo	Placebo

Primary Outcome Measures

Name	Time	Method
At least one relevant symptomatic or asymptomatic atrial fibrillation event	From D1 to M12

Secondary Outcome Measures

Name	Time	Method
All relevant cardiovascular event	From D1 to M12
Secondary effects of the treatment	From D1 to M12

Trial Locations

Locations (8)

CHU de Brest; 🇫🇷 Brest, France

CHU de Clermont-Ferrand; 🇫🇷 Clermont Ferrand, France

CHU de Montpellier; 🇫🇷 Montpellier, France

Polyclinique des Fleurs; 🇫🇷 Ollioules, France

CHU de Grenoble; 🇫🇷 Grenoble, France

CHU de Rouen; 🇫🇷 Rouen, France

CHU de Saint-Etienne; 🇫🇷 Saint-etienne, France

CHU de Rennes; 🇫🇷 Rennes, France