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

Sponsor

Centre Hospitalier Universitaire de Saint Etienne (Other)

Overall Status

Terminated

CT.gov ID

NCT00736294

Collaborator

Sanofi (Industry), Ministry of Health, France (Other), LivaNova (Industry)

198

Enrollment

Locations

Arms

Duration (Months)

24.8

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation Atrial Flutter	Drug: Ramipril Drug: Placebo	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

198 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2008

Actual Primary Completion Date :

Mar 1, 2015

Actual Study Completion Date :

Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ramipril Inhibition Conversion Enzyme	Drug: Ramipril 5 mg/d from D1 to M3 10 mg/d from M3 to M12 Tablets
Placebo Comparator: Placebo Placebo	Drug: Placebo 5 mg/d from D1 to M3 10 mg/d from M3 to M12 Tablets

Arm

Intervention/Treatment

Experimental: Ramipril

Inhibition Conversion Enzyme

Drug: Ramipril

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

Placebo Comparator: Placebo

Placebo

Drug: Placebo

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

Outcome Measures

Primary Outcome Measures

At least one relevant symptomatic or asymptomatic atrial fibrillation event [From D1 to M12]

Secondary Outcome Measures

All relevant cardiovascular event [From D1 to M12]
Secondary effects of the treatment [From D1 to M12]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	CHU de Brest	Brest	France	29609
2	CHU de Clermont-Ferrand	Clermont Ferrand	France	63003
3	CHU de Grenoble	Grenoble	France	38043
4	CHU de Montpellier	Montpellier	France	34295
5	Polyclinique des Fleurs	Ollioules	France	83190
6	CHU de Rennes	Rennes	France	35033
7	CHU de Rouen	Rouen	France	76031
8	CHU de Saint-Etienne	Saint-etienne	France	42 055