EARLY treatment with Candesartan vs Placebo in asymptomatic GENEtic carriers of Dilated Cardiomyopathy (EARLY-GENE trial)

Phase 1

Recruiting

Conditions: Genetic carriers of dilated cardiomyopathy causing variants
MedDRA version: 20.0Level: LLTClassification code: 10056419Term: Dilated cardiomyopathy Class: 10007541
MedDRA version: 22.0Level: PTClassification code: 10064571Term: Gene mutation Class: 100000004850
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Registration Number: CTIS2023-507029-40-00

Lead Sponsor: Fundacion Para La Investigacion Biomedica Del Hospital Universitario Puerta De Hierro Majadahonda

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 320

Inclusion Criteria

Age: 18-64 (both included), both sexes, Carrier of a pathogenic or likely pathogenic DCM genetic variant according to modified American College of Medical Genetics (ACMG) criteria, Baseline LVEF = 50% measured by MRI evaluated by the eligibility study committee. Carriers with myocardial fibrosis, detected by late gadolinium enhancement in magnetic resonance, are valid., Baseline potassium = 5.3 mEq/L, creatinine = 1.3 mg/dL and an estimated Glomerular Filtration Rate (eGFR)= 60 ml/min/1.73 m2, Able to understand and accept the study constraints and to provide informed consent.

Exclusion Criteria

Hypotension (systolic arterial pressure <100 mmHg), Presence of any contraindications to receive candesartan treatment, including severe liver failure and/or cholestasis, Known bilateral renal artery stenosis, Uncontrolled concomitant severe disease (e.g., with expected survival inferior to the duration of the study follow-up), Participation in another clinical trial using an investigational medicinal product or device, in the 30 days prior to the inclusion in the study, Current pregnancy, breastfeeding, or women of childbearing age who are not willing to practice an adequate birth control during the duration of the study (a negative pregnancy test result must be obtained at the time of enrolment), Drug or alcohol abuse (current), Inability to adequately comply with study procedures and treatments, Carriers of MRI incompatible internal devices (ICD, pacemakers, aneurysm clips, etc.) or with known intolerance to MRI studies, Any circumstances that in the investigator’s opinion compromise the participant’s ability to participate in the clinical trial, Prior ventricular dysfunction (LVEF = 50% at any time prior to study inclusion), Candidates who are expected or highly likely to receive an implantable cardioverter defibrillator (ICD) in the following 12 months after inclusion in the trial, Preexisting hypertension requiring pharmacological treatment, Uncontrolled arterial hypertension (i.e., repeatedly systolic arterial pressure = 140 mmHg), Carriers of TTN-truncating variants (TTNtv) who are < 35 years old, Known, clinically significant coronary artery disease (=70% stenosis in any epicardial artery or =50% of left main coronary artery), valvular disease (= moderate in severity) or ventricular arrhythmias, Ongoing treatment with ACE inhibitors, ARB, ARNI, MRA, Prior intolerance to ACE inhibitors or ARB

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess if early administration of candesartan (compared to placebo) prevents either a significant Left ventricular ejection fraction (LVEF) decline of =10%, or a ventricular dilatation (left ventricular end-diastolic volume, LVEDV) increase of =10% in genetic carriers of a DCM-causing variant without disease expression.;Secondary Objective: To assess if early administration of candesartan (compared to placebo) reduces or prevents any sign of progression to DCM (LVEF decline, LVEDV increase, or LVEF<50%, assessed by MRI) in genetic carriers of a DCM-causing variant without disease expression., To assess the safety and tolerability of candesartan (compared to placebo) in the study population;Primary end point(s): Proportion of participants that progress to either a LVEF or LVEDV deterioration of =10% with respect to the baseline value at the end of follow-up as measured by MRI

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):Proportion of participants that progress to a LVEDV deterioration of =10% compared to baseline value at the end of follow-up as measured by MRI.;Secondary end point(s):Changes in LVEF measured by MRI (vs baseline);Secondary end point(s):Changes in LVEDV measured by MRI (vs baseline);Secondary end point(s):Proportion of individuals who develop DCM (LVEF<50%);Secondary end point(s):Proportion of participants in each treatment group developing Serious Adverse Events (SAEs), Grade 3-4 adverse events (AEs), Adverse Reactions, or AEs of Special Interest (AESIs);Secondary end point(s):Proportion of treatment discontinuations in the candesartan and placebo groups;Secondary end point(s):Proportion of participants that progress to a LVEF deterioration of =10% compared to baseline value at the end of follow-up as measured by MRI