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

NCT ID: NCT05321875

Last Updated: 2024-11-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 320 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-02
• Study Completion Date: 2026-06-02

Brief Summary

Prospective, multicenter, randomized, placebo-controlled, double-blind clinical trial to evaluate safety and efficacy of candesartan in the prevention of the development of Dilated Cardiomyopathy (DCM) in genetic carriers of a DCM-causing variant without disease expression (asymptomatic)

Detailed Description

Prospective, multicenter, randomized, placebo-controlled, double-blind clinical trial to evaluate safety and efficacy of early administration of candesartan in the prevention of the development of Dilated Cardiomyopathy (DCM) in genetic carriers of a DCM-causing variant without disease expression (asymptomatic).

Randomization will be 1:1 and patients are allocated to candesartan or matching placebo.

Patients will be followed for a 3 years period and efficacy will be demonstrated if 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% within a 3-years period of follow-up

Conditions

Cardiomyopathy, Dilated

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Candesartan

Candesartan, 16 mg oral tablets. Target dose 32 mg or maximum tolerated dose after dose escalation from 16 mg

Group Type: EXPERIMENTAL

Candesartan

Intervention Type: DRUG

3 years treatment with candesartan target dose: 32 mg or maximum tolerated dose after dose escalation from 16 mg

Placebo

Matching placebo. Target dose 2 tablets or maximum tolerated dose after dose escalation from 1 tablet

Group Type: PLACEBO_COMPARATOR

Candesartan

Intervention Type: DRUG

3 years treatment with candesartan target dose: 32 mg or maximum tolerated dose after dose escalation from 16 mg

Interventions

Candesartan

3 years treatment with candesartan target dose: 32 mg or maximum tolerated dose after dose escalation from 16 mg

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cristina Avendaño Solá

OTHER

Sponsor Role: lead

Responsible Party

Cristina Avendaño Solá

Head of Clinical Pharmacology Department

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Pablo García-Pavía, MD, PhD

Role: STUDY_CHAIR

Hospital Universitario Puerta de Hierro Majadahonda

Locations

Hospital Universitario Puerta de Hierro-Majadahonda

Majadahonda, Madrid, Spain

Site Status: RECRUITING

Countries

Spain

Central Contacts

Cristina Avendaño-Solá, MD, PhD

Role: CONTACT

cavendano@salud.madrid.org

+34 91 1916479

Ana Velasco-Iglesias, Msc,PhD

Role: CONTACT

avelasco.idiphim@gmail.com

+34 91 1917867

Facility Contacts

Cristina Avendaño, MD

Role: primary

cavendano@salud.madrid.org

Other Identifiers

2021-004577-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EARLY-GENE

Identifier Type: -

Identifier Source: org_study_id