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

Launched by CRISTINA AVENDAÑO SOLÁ · Apr 1, 2022

Keywords

ClinConnect Summary

The EARLY-GENE Trial is a clinical study designed to see if a medication called candesartan can help prevent dilated cardiomyopathy (DCM) in people who carry a specific genetic variant associated with this heart condition but do not currently show any symptoms. This study is particularly focused on individuals aged 18 to 64 who have a certain genetic mutation linked to DCM, and whose heart function is still normal. Participants will be randomly assigned to either receive candesartan or a placebo (a dummy treatment) to compare the effects of the medication.

To join this trial, you need to be between 18 and 64 years old, a carrier of the genetic variant related to DCM, and in good health with a normal heart function. Participants will undergo regular assessments, including MRI scans to check heart health. It’s important to note that certain health conditions, like uncontrolled high blood pressure or serious heart issues, may prevent someone from taking part in the trial. If you qualify and choose to participate, you will be helping researchers understand how to better manage and possibly prevent heart problems in those at risk.

Gender

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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.