E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Patients carrying a mutation responsible for dilated cardiomyopathy and who are at a preclinical stage of the disease. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10056419 |
E.1.2 | Term | Dilated cardiomyopathy |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- Study the impact of ACE inhibitors (ACEi) in subjects who carry a mutation but have not yet developed DCM through a double blind randomized (parallel group) multicenter trial. - to extend the medical impact of predictive genetic testing in DCM (direct therapeutic impact). |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- adults: 18-60 years - carriers of the mutation has been identified in the family as associated wit DCM and who have received appropriate genetic counselling before and after the announcement of the genetic result - at least one family member should have a clinical diagnosis of dilated cardiomyopathy - no obvious DCM assessed - presence of minor LV abnormality: isolated LVEDD >112% or reduced systolic dysfunction : LVEF <55%, as assessed on echocardiography - able to provide informed consent and signed consent. |
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E.4 | Principal exclusion criteria |
* Subject < 18 years old or > 60 years * 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 (prior intolerance or adverse reaction, e.g. angio-oedeme, patients with hereditary or idiopathic angioedema, hypersensitivity to perindopril or any of the excipients (e.g. hereditary problems of galactose intolerance, glucose galactose malabsorption, or the Lapp lactase deficiency)) * Impaired renal function (serum creatinine > 150 micromol/l). * 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 who are already treated with ACE inhibitor or 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. * Participants treated with lithium * participant under legal guardianship |
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E.5 End points |
E.5.1 | Primary end point(s) |
occurence of DCM or deterioration of LV end-diastolic diameter / volume or deterioration of Ejection fraction; all criteria determined either by Echocardiography or by magnetic resonance imaging (MRI) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Echocardiography: 1, 2, 3 years magnetic resonance imaging (MRI): 3 years |
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E.5.2 | Secondary end point(s) |
- echocardiographic deterioration of LVEDD or ejection fraction - MRI deterioration of LVEDVol or Ejection fraction - occurence of DCM - Deterioration of other Echocardiographic parameters: TDI velocities (average Sa & Ea velocities) at the mitral annulus (lateral and septal), and the E/Ea ratio TDI 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) - 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) - other planned end-point but without sufficient statistical power: symptoms (dyspnoea: NYHA stage 1 to 4); hospitalisation (not planned) for heart failure); Safety end-point: nos excess of all cause death, cardiovascular death |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
biological analysis: last visit
Echocardiography: 1, 2, 3 years magnetic resonance imaging (MRI): 3 years |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |