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

NCT05321875 | Recruiting Phase 3

• 2 other identifiers: EARLY-GENE2021-004577-30
• Study Type: interventional
• Target: 320
• Locations: 1 country
• Sites: 1

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)

Conditions

Cardiomyopathy, Dilated

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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

  3 years

Secondary Outcomes (7)

• 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.

  3 years

• 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.

  3 years

• Changes in LVEF measured by MRI (vs baseline)

  3 years

• Changes in LVEDV measured by MRI (vs baseline)

  3 years

• Proportion of individuals who develop DCM (LVEF<50%).

  3 years

Other Outcomes (1)

• Proportion of participants developing new cardiac fibrosis and its extent measured by MRI in the candesartan and placebo groups.

  3 years

Study Arms (2)

Candesartan

EXPERIMENTAL

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

Drug: Candesartan

Placebo

PLACEBO COMPARATOR

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

Drug: Candesartan

Interventions

Candesartan DRUG

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

Candesartan; Placebo

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• Hypotension (systolic arterial pressure \<100 mmHg (measured following a standardized methodology).
• 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)
• 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.

Sponsors & Collaborators

• Cristina Avendaño Solá: lead

Study Sites (1)

Hospital Universitario Puerta de Hierro-Majadahonda

Majadahonda, Madrid, 28222, Spain

RECRUITING

MeSH Terms

Conditions

Cardiomyopathy, Dilated

Interventions

candesartan

Condition Hierarchy (Ancestors)

Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Cardiomyopathies; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Pablo García-Pavía, MD, PhD

  Hospital Universitario Puerta de Hierro Majadahonda

  STUDY CHAIR

Central Study Contacts

Cristina Avendaño-Solá, MD, PhD

CONTACT

+34 91 1916479; cavendano@salud.madrid.org

Ana Velasco-Iglesias, Msc,PhD

CONTACT

+34 91 1917867; avelasco.idiphim@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Identical placebo tablets manufactured by the same Manufacturer of active marketed Candesartan (KERN PHARMA). Double-blind labelling specific for the study.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of Clinical Pharmacology Department

Study Record Dates

• First Submitted: April 1, 2022
• First Posted: April 11, 2022
• Study Start: June 2, 2022
• Primary Completion (Estimated): June 2, 2026
• Study Completion (Estimated): June 2, 2026
• Last Updated: November 7, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: After study scientific publication
• Access Criteria: Under request to Study Chair

Locations

ES (1)