PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
Information source: Institut National de la Santé Et de la Recherche Médicale, France
Information obtained from ClinicalTrials.gov on February 07, 2013
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Dilated Cardiomyopathy
Intervention: perindopril (Drug); placebo (Drug)
Phase: Phase 3
Sponsored by: Institut National de la Santé Et de la Recherche Médicale, France
Official(s) and/or principal investigator(s):
PHILIPPE CHARRON, Principal Investigator, Affiliation: PITIE SALPETRIERE HOSPITAL, PARIS, FRANCE
This is a multicentre European double-blind,randomized and controlled trial with 2 parallel
groups (1 study medication, 1 placebo) in order to analyse the impact of ACE inhibitors
(ACEi) in subjects who carry a mutation but have not yet developed DCM (dilated
Objective of the trial: Study the impact of ACE inhibitors (ACEi) in subjects who carry a
mutation (leading to a genetic form of heart failure) but have not yet developed DCM.
Context. Dilated Cardiomyopathy (DCM) is one of the leading causes of Heart Failure due to
systolic dysfunction and at least 30% of DCM are of familial/genetic origin, usually with
autosomal dominant inheritance, and underlying genes and mutations are increasingly
identified. Familial Dilated Cardiomyopathy (fDCM) is characterized by age-related
penetrance (or delayed-onset), that means that the cardiac expression of the disease
(echocardiographic abnormalities) is usually absent for a long period and progressively
appears with advanced age, usually after 20 years of age
Hypothesis : ACEi may delay or prevent the occurrence of DCM in these subjects (pre-clinical
Expected results: If the hypothesis is confirmed, and as a consequence, the knowledge
derived from basic research (genes identification in DCM) will be translated into clinical
practice (early identification of subjects at high risk of developing heart failure through
predictive genetic testing) with the development of new therapeutic management (early ACEi)
that will help to decrease the morbidity and mortality associated with the disease. This
will constitute a paradigm of the development of preventive medicine thanks to the
development of genetics in the cardiovascular field.
Subjects who are concerned are â‰¥18 years of age and â‰¤60 years, carry a mutation responsible
for DCM and are at a preclinical stage of the disease. Total duration of treatment
(perindopril versus placebo) is 3 years. A total number of 200 participants will be enrolled
(100 in each group) in 7 centres.
Official title: Preventive Effect of ACE Inhibitor Perindopril)on the Onset or Progression of Left Ventricular Dysfoction in Subjects at a Preclinical Stage From Families With Dilated Cardiomyopathy
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Primary outcome: Change in left ventricle diameter / volume / ejection fraction
Echocardiographic deterioration of LVEDD or Ejection fraction
MRI - deterioration of LVEDVol or Ejection fraction
Occurence of DCM (Echo: EF< 45% and LVEDD>112%, ref Mahon, 2005)
Deterioration of other Echocardiographic parameters
Deterioration of hormonal biomarkers in serum
Clinical end-point: death
This study is part of a broader research program, "INHERITANCE" (INtegrated HEart Research
In TrANslational genetics of dilated Cardiomyopathies in Europe) research project, submitted
to EU (FP7 European Union, HEALTH-2009-2. 4.2-3: Translation of basic knowledge on inherited
cardiomyopathies into clinical practice) and accepted in 2009 (Grant agreement nÂ° 241924,
global coordinator: Pr Eloisa Arbustini, Pavia, Italy).
- Precardia / clinical trial Principal Investigator: Dr Philippe Charron, PitiÃ©
SalpÃªtriÃ¨re hospital, France
- FP7 Global Inheritance network coordinator: Pr Eloisa Arbustini, Italia
Minimum age: 18 Years.
Maximum age: 60 Years.
- Age: â‰¥18 years and â‰¤60 years
- At least one family member should have a clinical diagnosis of dilated cardiomyopathy
(LVEF<45% and LVEDD>112%)and should not be considered as the burn-out phase of
another cardiomyopathy (such as HCM, ARVC). LV noncompaction may co-exist with DCM in
this patient. NB: in a patient with a mutation in LMNA gene, LVEDD may be normal
whereas EF is markedly reduced, so that only a reduced LVEF is mandatory(LVEF<45%).
- Carriers of the mutation that has been identified in the family as associated with
DCM, and who have received appropriate genetic counselling before and after the
announcement of the genetic result. The mutation within the family should be
considered as disease-causing.
- No obvious DCM as assessed by diagnostic criteria indicated elsewhere on
echocardiography (WHO & Mestroni et al. 1999 and Mahon et al. 2005: references 3 and
9): LVEF <45% and enlarged LVEDD (>112% of predicted value according to age,BSA).
- Presence of minor LV abnormality:
- isolated LVEDD > 112% (Henry Formula)
- or reduced systolic dysfunction: 45% < LVEF < 55%, as assessed on
- Able to provide informed consent, and signed informed consent.
- Able to understand and accept the study constraints
- For some European countries (such as France and Spain): participants (by themselves)
should have medical health care coverage to be included in a research study
- Other disease or factor that can cause minor LV abnormalities, such as cardiotoxic
treatment or significant blood hypertension (with uncontrolled blood pressure or
significant hypertrophy on echocardiography).
- Contraindication to ACE inhibitor
- Participants who are already treated with ACE inhibitor, sartan or aldosterone
receptor antagonists (for various reason such as arterial hypertension) can not be
included in this study, unless they have been off these drugs for a period of 6 weeks
- Impaired renal function: estimated Glomerular Filtration Rate (eGFR), using MDRD
formula, < 60 ml/mn/1. 73m2.
- Baseline serum potassium >5. 5 mmol/L.
- Pregnant, parturient or breastfeeding woman or woman of childbearing potential not
under effective contraception or planned pregnancy.
- Participation in another therapeutic trial in the previous 3 months
- Participants treated with lithium
- Participant under legal guardianship
Locations and Contacts
Skejby University Hospital SUH, Aarhus Universit Hospital, Aarhus 8200, Denmark; Not yet recruiting
Jens Mogensen, MD, Phone: +45 89496199, Email: firstname.lastname@example.org
Jens MOGENSEN, MD, Principal Investigator
PitiÃ© SalpÃªtriÃ¨re Hospital, Paris 75013, France; Recruiting
Philippe CHARRON, MD-PhD, Phone: +33 (0)1 42 16 13 47, Email: email@example.com
Philippe CHARRON, MD-PhD, Principal Investigator
University of Heidelberg UKLHD, Heidelberg 69120, Germany; Not yet recruiting
Hugo KATUS, Pr, Phone: +49-6221-56-8670, Email: firstname.lastname@example.org
Hugo KATUS, Pr, Principal Investigator
Academic Hospital IRCCS Foundation Policlinico San Matteo (OSM), Pavia 27100, Italy; Not yet recruiting
Eloisa ARBUSTINI, Pr, Phone: +39 0382 501893, Email: email@example.com
Eloisa ARBUSTINI, Pr, Principal Investigator
Academisch Medisch Centrum AMC and InterUniversity Institute AMC/ICIN, Amsterdam 1105 AZ, Netherlands; Not yet recruiting
Yigal PINTO, MD, Phone: +31-20-5664927, Email: firstname.lastname@example.org
Yigal PINTO, MD, Principal Investigator
Health in Code SL (SME) - Hospital MarÃtimo de Oza., A CoruÃ±a 15006, Spain; Not yet recruiting
Lorenzo MONSERRAT, MD, Phone: +34 981167000, Ext: 5929, Email: email@example.com
Lorenzo MONSERRAT, MD, Principal Investigator
The Heart Hospital, University College London NHS Foundation Trust, London W1G 8PH, United Kingdom; Not yet recruiting
Perry ELLIOTT, MD, Phone: +44-20-7573 8888, Email: firstname.lastname@example.org
Perry ELLIOTT, MD, Principal Investigator
Precardia study is part of global european project INHERITANCE
Starting date: December 2011
Last updated: April 19, 2012