EARLY treatment with Candesartan vs Placebo in asymptomatic GENEtic carriers of Dilated Cardiomyopathy (EARLY-GENE trial)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Para La Investigacion Biomedica Del Hospital Universitario Puerta De Hierro Majadahonda

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16], Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

9 May 2022 → ongoing

Decision date (initial)

2024-04-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ISCIII

External identifiers

EU CT number

2023-507029-40-00

EudraCT number

2021-004577-30

ClinicalTrials.gov

NCT05321875

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To assess if early administration of 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% in genetic carriers of a DCM-causing variant without disease expression.

Secondary objectives 2

1. To assess if early administration of candesartan (compared to placebo) reduces or prevents any sign of progression to DCM (LVEF decline, LVEDV increase, or LVEF<50%, assessed by MRI) in genetic carriers of a DCM-causing variant without disease expression.
2. To assess the safety and tolerability of candesartan (compared to placebo) in the study population

Conditions and MedDRA coding

Genetic carriers of dilated cardiomyopathy causing variants

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age: 18-64 (both included), both sexes
2. Carrier of a pathogenic or likely pathogenic DCM genetic variant according to modified American College of Medical Genetics (ACMG) criteria
3. Baseline LVEF ≥ 50% measured by MRI evaluated by the eligibility study committee. Carriers with myocardial fibrosis, detected by late gadolinium enhancement in magnetic resonance, are valid.
4. Baseline potassium ≤ 5.3 mEq/L and creatinine ≤ 1.3 mg/dL.
5. Able to understand and accept the study constraints and to provide informed consent.

Exclusion criteria 18

1. Hypotension (systolic arterial pressure <100 mmHg)
2. Prior ventricular dysfunction (LVEF ≤ 50% at any time prior to study inclusion)
3. Candidates who are expected or highly likely to receive an implantable cardioverter defibrillator (ICD) in the following 12 months after inclusion in the trial
4. Preexisting hypertension requiring pharmacological treatment
5. Uncontrolled arterial hypertension (i.e., repeatedly systolic arterial pressure ≥ 140 mmHg)
6. Carriers of TTN-truncating variants (TTNtv) who are < 35 years old
7. Known, clinically significant coronary artery disease (≥70% stenosis in any epicardial artery or ≥50% of left main coronary artery), valvular disease (≥ moderate in severity) or ventricular arrhythmias
8. Ongoing treatment with ACE inhibitors, ARB, ARNI, MRA
9. Prior intolerance to ACE inhibitors or ARB
10. Presence of any contraindications to receive candesartan treatment, including severe liver failure and/or cholestasis
11. Known bilateral renal artery stenosis
12. Uncontrolled concomitant severe disease (e.g., with expected survival inferior to the duration of the study follow-up)
13. Participation in another clinical trial using an investigational medicinal product or device, in the 30 days prior to the inclusion in the study
14. Current pregnancy, breastfeeding, or women of childbearing age who are not willing to practice an adequate birth control during the duration of the study (a negative pregnancy test result must be obtained at the time of enrolment)
15. Drug or alcohol abuse (current)
16. Inability to adequately comply with study procedures and treatments
17. Carriers of MRI incompatible internal devices (ICD, pacemakers, aneurysm clips, etc.) or with known intolerance to MRI studies
18. Any circumstances that in the investigator’s opinion compromise the participant’s ability to participate in the clinical trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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

Secondary endpoints 7

1. 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
2. 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. Changes in LVEF measured by MRI (vs baseline)
4. Changes in LVEDV measured by MRI (vs baseline)
5. Proportion of individuals who develop DCM (LVEF<50%)
6. 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)
7. Proportion of treatment discontinuations in the candesartan and placebo groups

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Para La Investigacion Biomedica Del Hospital Universitario Puerta De Hierro Majadahonda

Sponsor organisation

Fundacion Para La Investigacion Biomedica Del Hospital Universitario Puerta De Hierro Majadahonda

Address

Calle De Joaquin Rodrigo 2

City

Majadahonda

Postcode

28222

Country

Spain

Scientific contact point

Organisation

Fundacion Para La Investigacion Biomedica Del Hospital Universitario Puerta De Hierro Majadahonda

Contact name

Pablo García Pavía

Public contact point

Organisation

Fundacion Para La Investigacion Biomedica Del Hospital Universitario Puerta De Hierro Majadahonda

Contact name

Pablo García Pavía

Locations

2 EU/EEA countries · 42 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications