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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Sanofi
Ministry of Health, France
Sorin Group
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Saint Etienne
ClinicalTrials.gov Identifier:
NCT00736294
First received: August 14, 2008
Last updated: July 23, 2014
Last verified: July 2014
  Purpose

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 Intervention Phase
Atrial Fibrillation
Atrial Flutter
Drug: Ramipril
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire de Saint Etienne:

Primary Outcome Measures:
  • At least one relevant symptomatic or asymptomatic atrial fibrillation event [ Time Frame: From D1 to M12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • All relevant cardiovascular event [ Time Frame: From D1 to M12 ] [ Designated as safety issue: No ]
  • Secondary effects of the treatment [ Time Frame: From D1 to M12 ] [ Designated as safety issue: Yes ]

Enrollment: 198
Study Start Date: July 2008
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00736294

Locations
France
CHU de Brest
Brest, France, 29609
CHU de Clermont-Ferrand
Clermont Ferrand, France, 63003
CHU de Grenoble
Grenoble, France, 38043
CHU de Montpellier
Montpellier, France, 34295
Polyclinique des Fleurs
Ollioules, France, 83190
CHU de Rennes
Rennes, France, 35033
CHU de Rouen
Rouen, France, 76031
CHU de Saint-Etienne
Saint-etienne, France, 42 055
Sponsors and Collaborators
Centre Hospitalier Universitaire de Saint Etienne
Sanofi
Ministry of Health, France
Sorin Group
Investigators
Principal Investigator: Antoine DA COSTA, PhD MD CHU de Saint-Etienne
  More Information

Publications:

Responsible Party: Centre Hospitalier Universitaire de Saint Etienne
ClinicalTrials.gov Identifier: NCT00736294     History of Changes
Other Study ID Numbers: 0608066, 2006-007032-10
Study First Received: August 14, 2008
Last Updated: July 23, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: French Data Protection Authority

Keywords provided by Centre Hospitalier Universitaire de Saint Etienne:
Catheter Ablation, Radiofrequency
Angiotensin-Converting Enzyme Inhibitors

Additional relevant MeSH terms:
Atrial Fibrillation
Atrial Flutter
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Angiotensin-Converting Enzyme Inhibitors
Ramipril
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014