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

Primary Purpose

Cardiomyopathy, Dilated

Status

Recruiting

Phase

Phase 3

Locations

Spain

Study Type

Interventional

Intervention

Candesartan

About this trial

This is an interventional prevention trial for Cardiomyopathy, Dilated focused on measuring Dilated Cardiomyopathy, Genetic Mutation Carrier, Randomized Clinical Trial, Genetic Dilated Cardiomyopathy

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Hospital Universitario Puerta de Hierro-MajadahondaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Candesartan

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.

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.

Changes in LVEF measured by MRI (vs baseline)

Changes in LVEDV measured by MRI (vs baseline)

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

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).

Proportion of treatment discontinuations in the candesartan and placebo groups.

Full Information

NCT ID

NCT05321875

First Posted

April 1, 2022

Last Updated

August 23, 2022

Sponsor

Cristina Avendaño Solá

1. Study Identification

Unique Protocol Identification Number

NCT05321875

Brief Title

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

Acronym

EARLY-GENE

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Recruiting

Study Start Date

June 2, 2022 (Actual)

Primary Completion Date

June 2, 2026 (Anticipated)

Study Completion Date

June 2, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Cristina Avendaño Solá

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cardiomyopathy, Dilated

Keywords

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

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Identical placebo tablets manufactured by the same Manufacturer of active marketed Candesartan (KERN PHARMA). Double-blind labelling specific for the study.

Allocation

Randomized

Enrollment

320 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Candesartan

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Candesartan

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Time Frame

3 years

Secondary Outcome Measure Information:

Title

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.

Time Frame

3 years

Title

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.

Time Frame

3 years

Title

Changes in LVEF measured by MRI (vs baseline)

Time Frame

3 years

Title

Changes in LVEDV measured by MRI (vs baseline)

Time Frame

3 years

Title

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

Time Frame

3 years

Title

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).

Time Frame

3 years

Title

Proportion of treatment discontinuations in the candesartan and placebo groups.

Time Frame

3 years

Other Pre-specified Outcome Measures:

Title

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

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

64 Years

Accepts Healthy Volunteers

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. 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Cristina Avendaño-Solá, MD, PhD

Phone

+34 91 1916479

cavendano@salud.madrid.org

First Name & Middle Initial & Last Name or Official Title & Degree

Ana Velasco-Iglesias, Msc,PhD

Phone

+34 91 1917867

avelasco.idiphim@gmail.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pablo García-Pavía, MD, PhD

Organizational Affiliation

Hospital Universitario Puerta de Hierro Majadahonda

Official's Role

Study Chair

Facility Information:

Facility Name

Hospital Universitario Puerta de Hierro-Majadahonda

City

Majadahonda

State/Province

Madrid

ZIP/Postal Code

28222

Country

Spain

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Cristina Avendaño, MD

cavendano@salud.madrid.org

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Under agreement, individual or aggregated patient data could be shared with other scientific groups for new scientific projects. Data can be shared only for scientific purposes and in full compliance with Personal Data Protection requirements in the EU

IPD Sharing Time Frame

After study scientific publication

IPD Sharing Access Criteria

Under request to Study Chair

Learn more about this trial

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

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