Dilated CardiomyopathyPhase 3PRECARDIANCT01583114
PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
A Phase 3 study testing perindopril in people with Dilated Cardiomyopathy, run by Institut National de la Santé Et de la Recherche Médicale, France at 7 sites in 7 countries.
Trial summary
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 cardiomyopathy). Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Dilated Cardiomyopathy
- What is being tested?
- perindopril
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 7 sitesin 7 countries
- Study dates
- Dec 2011to Jan 2014
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age: ≥18 years and ≤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)
Show all 10Show fewer
- or reduced systolic dysfunction: 45% < LVEF < 55%, as assessed on echocardiography.
- 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
Who cannot join
- 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 before inclusion.
- 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.
Show all 9Show fewer
- Participation in another therapeutic trial in the previous 3 months
- Participants treated with lithium
- Participant under legal guardianship
Trial locations and contacts
7 sites in 7 countries.
7 sites in 7 countries
Denmark1 site
Skejby University Hospital SUH, Aarhus Universit Hospital
Aarhus, 8200
Italy1 site
Academic Hospital IRCCS Foundation Policlinico San Matteo (OSM)
Pavia, 27100
Netherlands1 site
Academisch Medisch Centrum AMC and InterUniversity Institute AMC/ICIN
Amsterdam, 1105 AZ
United Kingdom1 site
The Heart Hospital, University College London NHS Foundation Trust
London, W1G 8PH
About this study
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
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 cardiomyopathy).
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.
Read more
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 stage).
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 ≥18 years of age and ≤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.
Read the detailed description
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 n° 241924, global coordinator: Pr Eloisa Arbustini, Pavia, Italy).
- Precardia / clinical trial Principal Investigator: Dr Philippe Charron, Pitié Salpêtrière hospital, France
- FP7 Global Inheritance network coordinator: Pr Eloisa Arbustini, Italia
- Conditions
- Dilated Cardiomyopathy
- Being tested
- perindopril, placebo
- Keywords
- dilated cardiomyopathy, heart failure, genetics, mutation carrier, ACE treatment, preclinical
- Medical subject headings
- Cardiomyopathy, Dilated, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
perindoprilDrug
Also called Coversyl
form:1 tablet contained 5 mg of perindopril; posology: 1 intake per day, initiated at a dose of 2.5 mg (1/2 tablet) per day during one week, then 5 mg (1 tablet) per day during two weeks, then 10 mg (2 tablets), or the maximal dose tolerated, until the end of the study (36 months).
placeboDrug
form:1 tablet contained 5 mg placebo; posology: 1 intake per day, initiated at a dose of 2.5 mg (1/2 tablet) per day during one week, then 5 mg (1 tablet) per day during two weeks, then 10 mg (2 tablets), or the maximal dose tolerated, until the end of the study (36 months).
| Study group | Role | What they receive |
|---|---|---|
| perindopril | Experimental | Not described Receives: Drug: perindopril |
| placebo | Placebo comparator | same form, administration, posology, frequency and duration as perindopril Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in left ventricle diameter / volume / ejection fraction
Primary composite end point:
- Occurence of DCM (LV ejection fraction LVEF<45% and LVEDD>112%)
- or deterioration of LV end-diastolic diameter / volume (occurrence of events defined as "+4% LVEDD/LVEDV")
- or deterioration of Ejection fraction (occurrence of events defined as "-4% LVEF")
All criteria determined either by Echocardiography (primary end-point 1) or by Magnetic resonance imaging (MRI) primary end-point 2).
Measured: baseline,12 months, 24 months and 36 months after inclusion
Secondary outcomes (7)
Echocardiographic deterioration of LVEDD or Ejection fraction
Echocardiographic deterioration of LVEDD (comparison of average "final LVEDD compared to baseline LVEDD" between arms) or Ejection fraction (comparison of average "final LVEF vs baseline LVEF" between arms)
Measured: at baseline and at 24 months and 36 months after inclusion
MRI - deterioration of LVEDVol or Ejection fraction
MRI deterioration of LVEDVol (comparison of average "final LVEDVol compared to baseline LVEDVol" between arms) or Ejection fraction (comparison of average "final LVEF vs baseline LVEF" between arms)
Measured: at baseline and at 36 months after inclusion
Occurence of DCM (Echo: EF< 45% and LVEDD>112%, ref Mahon, 2005)
Occurence of DCM on Echocardiography: EF< 45% and LVEDD>112% (ref Mahon, 2005)
Measured: baseline, 12 months, 24 months and 36 months after inclusion
Deterioration of other Echocardiographic parameters
Deterioration of other Echocardiographic parameters:
- TDI velocities (average Sa \& Ea velocities) at the mitral annulus (lateral and septal), and the E/Ea ratio
- strain and strain rate (radial, longitudinal, circonferential strain rate in the basal, mid and apical segments)
- LV volumes (LVED Vol and LVES Vol, Simpson method, 4 cavity incidence)
Measured: at baseline, at 12 months, 24 months and 36 months after inclusion
Deterioration of hormonal biomarkers in serum
Deterioration of hormonal biomarkers in serum:
- Natriuretic peptid: BNP and NTproBNP (+/-4% or final versus baseline).
- Mid-Regional pro-Adrenomedullin (MR-proADM) and Mid-Regional proANP, (+/-4% or final versus baseline).
Measured: at baseline, at 18 months and 36 months after inclusion
Clinical end-point
Clinical end-point (statistical power is known to be sufficient):
- Symptoms: Dyspnoea (NYHA stage 1 to 4)
- Hospitalisation (not planed) for heart failure
Measured: at each visit (inclusion, at 2 weeks, 3 months, 6 months, then every 6 months to 36 months after inclusion)
Clinical end-point: death
Clinical end-point (statistical power is known to be sufficient):
- All cause death
- cardiovascular death (Safety end-point: no excess of)
Measured: at each visit (inclusion, at 2 weeks, 3 months, 6 months, then every 6 months to 36 months after inclusion)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2012 (estimated)
- Study startDec 2011
- Primary completionJan 2014
- Study completionJan 2014
Why it stopped: recruitement problem
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Dilated CardiomyopathyStudies of the same condition, open and under way.
- More trials run by Institut National de la Santé Et de la Recherche Médicale, FranceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- PHILIPPE CHARRON, Principal investigator, PITIE SALPETRIERE HOSPITAL, PARIS, FRANCE
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01583114
- Sponsor's protocol ID
- C10-44
- Other IDs
- 2010-023184-18
- Acronym
- PRECARDIA
- Status last verified
- Feb 2016
- First submitted
- 11 Apr 2012
- Last updated
- 24 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes