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Blockade of the Renin-angiotensin-aldosterone System in Patients With ARVD (BRAVE)

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ClinicalTrials.gov Identifier: NCT03593317
Recruitment Status : Not yet recruiting
First Posted : July 20, 2018
Last Update Posted : July 20, 2018
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

Brief Summary:

Arrhythmogenic right ventricular dysplasia (ARVD) is a rare cardiomyopathy characterized by the progressive replacement of cardiomyocytes by fatty and fibrous tissue in the right ventricle (RV). These infiltrations lead to cardiac electrical instability and ventricular arrhythmia.

Current treatment for ARVD is empirical and essentially based on treatment of arrhythmia. Thus, there is no validated treatment that will prevent the deterioration of the RV function in patients with ARVD.

The investigator's hypothesis is that the use of anti-fibrotic medications will prevent or at least reduce the deterioration of the RV function. The aim of this project is to evaluate the effect of Ramipril, an angiotensin-converting enzyme inhibitor, on ventricular myocardial remodeling and on arrhythmia burden in patients with ARVD.

The trial is a double-blind parallel multicenter prospective randomized phase IV drug study. Patients will be randomized in the two groups: ramipril or placebo. 26 centers in France will enroll the 120 patients (60 per group). Patients will be followed up every 6 months for 3 years. A decrease in right and/or left ventricular deterioration and in arrhythmia burden are expected in ARVD patients treated with ramipril. This reduction will improve the quality of life of patients and will reduce the number of hospitalizations and the risk of terminal heart failure.


Condition or disease Intervention/treatment Phase
Arrhythmogenic Right Ventricular Dysplasia Drug: Ramipril Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Blockade of the Renin-angiotensin-aldosterone System in Patients With ARVD: a Double-blind Multicentre Prospective Randomized Study.
Estimated Study Start Date : January 2019
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : January 2023


Arm Intervention/treatment
Experimental: Ramipril group Drug: Ramipril
The doses used in the study are the doses used in standard clinical practice. The dose will be adjusted in steps of 2.5 mg every week until the optimal dose. The optimal dose is usually between 5mg to 10mg per day. Ramipril must be taken before, during or after meals; Ramipril will be take once a day at the same time of day. The duration of treatment for each patient is 36 months.

Placebo Comparator: Placebo group Drug: Placebo
Placebo will be take once a day at the same time of day. The duration of treatment for each patient is 36 months.




Primary Outcome Measures :
  1. Right ventricle volume measured by MRI [ Time Frame: at year 3 ]
  2. number of ventricular extrasystoles on 24h-Holter ECG [ Time Frame: at year 3 ]

Secondary Outcome Measures :
  1. left ventricle measured by MRI [ Time Frame: at year 3 ]
    Morphologic criterion

  2. left ventricle measured by echocardiography [ Time Frame: at year 3 ]
    Morphologic criterion

  3. aneurism measured by MRI [ Time Frame: at year 3 ]
    Morphologic criterion

  4. aneurism measured by echocardiography [ Time Frame: at year 3 ]
    Morphologic criterion

  5. dyskinesia measured by MRI [ Time Frame: at year 3 ]
    Morphologic criterion

  6. dyskinesia measured echocardiography [ Time Frame: at year 3 ]
    Morphologic criterion

  7. evolution of QRS width (50mm/s) on ECG [ Time Frame: at year 3 ]
    Morphologic criterion

  8. number of ventricular extrasystoles on 24h Holter ECG [ Time Frame: at year 3 ]
    Rhythmic criterion

  9. sustained ventricular tachycardia on 24h Holter ECG [ Time Frame: at year 3 ]
    Rhythmic criterion

  10. evolution of PR interval duration on ECG [ Time Frame: at 6 month ]
    Rhythmic criterion

  11. late potentials measured with high amplification ECG [ Time Frame: at year 3 ]
    Rhythmic criterion

  12. number of ventricular extrasystoles by stress test [ Time Frame: at year 3 ]
    Rhythmic criterion

  13. Evolution of functional symptoms by recording adverse events [ Time Frame: at year 3 ]
    Functional criteria

  14. Number of hospital admissions owing to clinical deterioration [ Time Frame: at year 3 ]
  15. Evolution of telediastolic right ventricle volume measured by MRI [ Time Frame: at year 3 ]
    according to the genotype of desmosome genes

  16. arrhythmia burden measured by 24h Holter ECG [ Time Frame: at year 3 ]
    according to the genotype of desmosome genes

  17. Dosage of MMP9 (Matrix metallopeptidase 9) [ Time Frame: at year 3 ]
    Quantification of fibrosis

  18. Dosage of TIMP1 (Tissue Inhibitory MetalloProtease 1) [ Time Frame: at year 3 ]
    Quantification of fibrosis

  19. Dosage of TIMP2 (Tissue Inhibitory MetalloProtease 2) [ Time Frame: at year 3 ]
    Quantification of fibrosis

  20. Dosage of IL6 (Interleukin 6) [ Time Frame: at year 3 ]
    Quantification of inflammation

  21. Dosage of IL8 (Interleukin 8) [ Time Frame: at year 3 ]
    Quantification of inflammation



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • >18years old
  • Diagnosis of ARVD based on Task Force criteria. Two major criteria: 1 morphologic and one rhythmic or 1 major and 2 minor criteria established by the European Society of Cardiology/International Society and Federation of Cardiology.
  • Increased right ventricular volume (> 100ml/m² female; > 110ml/m² male)
  • Left Ventricular Ejection Fraction >40%
  • Written informed consent.

Exclusion Criteria:

  • Pregnancy.
  • No health insurance.
  • MRI contraindication (claustrophobia, implantable defibrillator).
  • Right heart failure patient (RV volume>150ml)
  • Ramipril contraindication (hypotension, renal failure).
  • Normal right ventricular volume
  • Heart transplantation
  • Swallowing disorders

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03593317


Contacts
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Contact: Elodie Morel, PhD 4 72 35 73 81 ext +33 elodie.morel01@chu-lyon.fr
Contact: Philippe Chevalier, MD, PhD 4 72 35 70 27 ext +33 philippe.chevalier@chu-lyon.fr

Locations
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France
Hôpital Cardiologique Louis Pradel Not yet recruiting
Bron, France
Contact: Philippe Chevalier         
Sponsors and Collaborators
Hospices Civils de Lyon
Investigators
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Principal Investigator: Philippe Chevalier, MD, PhD Hospices Civils de Lyon

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Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT03593317     History of Changes
Other Study ID Numbers: 69HCL18_0038
First Posted: July 20, 2018    Key Record Dates
Last Update Posted: July 20, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hospices Civils de Lyon:
Heart Failure
Right ventricle
Additional relevant MeSH terms:
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Arrhythmogenic Right Ventricular Dysplasia
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Cardiomyopathies
Heart Diseases
Congenital Abnormalities
Ramipril
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents