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

Phase 1

Conditions: Dilated Cardiomyopathy
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Registration Number: EUCTR2021-004577-30-ES

Lead Sponsor: FUNDACION INVESTIGACION BIOMEDICA HOSPITAL PUERTA DE HIERRO MAJADAHONDA

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

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 the modified American College of Medical Genetics (ACMG) criteria.
- Baseline LVEF = 50% measured by MRI evaluated by the eligibility study committee.
- 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 (either by themselves or by a legal representative).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 320
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- Hypotension (systolic arterial pressure <100 mmHg)
- 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.
- Presence of any contraindications to receive candesartan treatment, per investigator’s opinion.
- 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 (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.

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.<br>- 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.;Timepoint(s) of evaluation of this end point: At the end of follow-up (36 months)

Secondary Outcome Measures

Name	Time	Method
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.<br>- 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.<br>- Changes in LVEF measured by MRI (vs baseline)<br>- Changes in LVEDV measured by MRI (vs baseline)<br>- Proportion of individuals who develop DCM (LVEF<50%).<br>- 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).<br>- Proportion of treatment discontinuations in the candesartan and placebo groups.;Timepoint(s) of evaluation of this end point: At the end of follow-up (36 months)

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