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

Cardiomyopathy, Dilated Clinical Trial

— EARLY-GENE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05321875
• Other study ID #: EARLY-GENE
• Secondary ID: 2021-004577-30
• Status: Recruiting
• Phase: Phase 3
• Start date: June 2, 2022
• Est. completion date: June 2, 2026

Study information

• Verified date: August 2022
• Source: Puerta de Hierro University Hospital
• Contact: Cristina Avendaño-Solá, MD, PhD
• Phone: +34 91 1916479
• Email: cavendano[@]salud.madrid.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 320
• Est. completion date: June 2, 2026
• Est. primary completion date: June 2, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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.

• 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 (either themselves or a legal representative).

Exclusion Criteria:

• Hypotension (systolic arterial pressure <100 mmHg as the mean value after 3 consecutive reads 5 minutes apart).

• 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 (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.

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Dilated

Intervention

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

Locations

Country	Name	City	State
Spain	Hospital Universitario Puerta de Hierro-Majadahonda	Majadahonda	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Cristina Avendaño Solá

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Proportion of participants developing new cardiac fibrosis and its extent measured by MRI in the candesartan and placebo groups.		3 years
Primary	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	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
Secondary	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
Secondary	Changes in LVEF measured by MRI (vs baseline)		3 years
Secondary	Changes in LVEDV measured by MRI (vs baseline)		3 years
Secondary	Proportion of individuals who develop DCM (LVEF<50%).		3 years
Secondary	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).		3 years
Secondary	Proportion of treatment discontinuations in the candesartan and placebo groups.		3 years