Candesartan treatment for genetic carriers of dilated cardiomyopathy

Early Treatment With Candesartan vs Placebo in Asymptomatic Genetic Carriers of Dilated Cardiomyopathy (EARLY-GENE Trial)"

This study is testing if the medication candesartan can help prevent heart problems in people who carry genes that could lead to dilated cardiomyopathy but don’t have symptoms yet.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 320 (estimated)
• Ages: 18 Years to 64 Years
• Sex: All
• Sponsor: Puerta de Hierro University Hospital (Academic / other)
• Locations: 1 site (Majadahonda, Madrid)
• Trial ID: NCT05321875 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of candesartan in preventing dilated cardiomyopathy (DCM) in asymptomatic genetic carriers of DCM-causing variants. It is a multicenter, randomized, placebo-controlled, double-blind study where participants are assigned to receive either candesartan or a matching placebo. Over a three-year follow-up period, the trial aims to determine if candesartan can prevent significant declines in left ventricular ejection fraction or increases in left ventricular end-diastolic volume. The study involves rigorous eligibility criteria to ensure the safety and appropriateness of participants.

Who should consider this trial

Good fit: Ideal candidates are asymptomatic individuals aged 18-64 who are carriers of a pathogenic or likely pathogenic DCM genetic variant.

Not a fit: Patients with prior ventricular dysfunction or those expected to receive an implantable cardioverter defibrillator within the next 12 months may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could prevent the onset of dilated cardiomyopathy in individuals at genetic risk, potentially improving their long-term heart health.

How similar studies have performed: While there have been studies on the treatment of dilated cardiomyopathy, this specific approach targeting genetic carriers is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

* Age: 18-64 (both included), both sexes
* Carrier of a pathogenic or likely pathogenic DCM genetic variant1 according to modified American College of Medical Genetics (ACMG) criteria.
* Baseline LVEF ≥ 50% measured by MRI1 and evaluated by the eligibility study committee. Carriers with myocardial fibrosis, detected by late gadolinium enhancement in magnetic resonance imaging, are valid.
* Baseline creatinine ≤1.3 mg/dL, potassium ≤ 5.3 mEq/L and an estimated Glomerular Filtration Rate (eGFR)≥ 60 ml/min/1.73 m2 calculated by CKD-EPI formula.
* Able to understand and accept the study constraints and to provide informed consent.

Exclusion Criteria:

* Hypotension (systolic arterial pressure \<100 mmHg (measured following a standardized methodology).
* 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 (e.g., ≥70% stenosis in any epicardial artery or ≥50% of left main coronary artery), valvular disease (≥ moderate in severity) or ventricular arrhythmias.
* Ongoing treatment with ACEI, ARB, ARNI or MRA.
* Prior intolerance to ACE inhibitors or ARB.
* 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 any other clinical trial using an investigational medicinal product or device in the 30 days previous 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 entire duration of the study (a negative pregnancy test result must be confirmed at the time of enrolment)\*.
* Drug or alcohol abuse (current).
* Inability to comply with study procedures and treatments.
* Carriers of MRI incompatible internal devices (ICD, pacemakers, aneurysm clips, etc.), with known intolerance to MRI studies or presenting any contraindications to perform cardiac MRI studies.
* Any circumstances that in the investigator's opinion compromise the participant's ability to participate in the clinical trial.

Where this trial is running

Majadahonda, Madrid

• Hospital Universitario Puerta de Hierro-Majadahonda — Majadahonda, Madrid, Spain (Recruiting)

Study contacts

• Study coordinator: Cristina Avendaño-Solá, MD, PhD

Conditions Cardiomyopathy, Dilated; Dilated Cardiomyopathy; Genetic Mutation Carrier; Randomized Clinical Trial; Genetic Dilated Cardiomyopathy