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

NCT00736294 | Terminated Phase 3 DMC

• 2 other identifiers: 06080662006-007032-10
• Study Type: interventional
• Target: 198
• Locations: 1 country
• Sites: 8

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.

Conditions

Atrial Fibrillation; Atrial Flutter

Keywords

Catheter Ablation, Radiofrequency; Angiotensin-Converting Enzyme Inhibitors

Outcome Measures

Primary Outcomes (1)

• At least one relevant symptomatic or asymptomatic atrial fibrillation event

  From D1 to M12

Secondary Outcomes (2)

• All relevant cardiovascular event

  From D1 to M12

• Secondary effects of the treatment

  From D1 to M12

Study Arms (2)

Ramipril

EXPERIMENTAL

Inhibition Conversion Enzyme

Drug: Ramipril

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Ramipril DRUG

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

Ramipril

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Saint Etienne: lead
• Sanofi: collaborator
• Ministry of Health, France: collaborator
• LivaNova: collaborator

Study Sites (8)

CHU de Brest

Brest, 29609, France

Location

CHU de Clermont-Ferrand

Clermont-Ferrand, 63003, France

Location

CHU de Grenoble

Grenoble, 38043, France

Location

CHU de Montpellier

Montpellier, 34295, France

Location

Polyclinique des Fleurs

Ollioules, 83190, France

Location

CHU de Rennes

Rennes, 35033, France

Location

CHU de Rouen

Rouen, 76031, France

Location

CHU de Saint-Etienne

Saint-Etienne, 42 055, France

Location

Related Publications (4)

• 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.

  PMID: 17030680 BACKGROUND

• 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.

  PMID: 15604348 BACKGROUND

• 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.

  PMID: 15511250 BACKGROUND

• 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.

  PMID: 10639539 BACKGROUND

MeSH Terms

Conditions

Atrial Fibrillation; Atrial Flutter

Interventions

Ramipril

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Antoine DA COSTA, PhD MD

  CHU de Saint-Etienne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2008
• First Posted: August 15, 2008
• Study Start: July 1, 2008
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: July 28, 2015

Record last verified: 2015-07

Locations

FR (8)