Early Treatment With Candesartan vs Placebo in Asymptomatic Genetic Carriers of Dilated Cardiomyopathy (EARLY-GENE Trial)"
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 320
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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)
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Identical placebo tablets manufactured by the same Manufacturer of active marketed Candesartan (KERN PHARMA). Double-blind labelling specific for the study.
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Candesartan
Candesartan, 16 mg oral tablets. Target dose 32 mg or maximum tolerated dose after dose escalation from 16 mg
干预措施: Candesartan (Drug)
Placebo
Matching placebo. Target dose 2 tablets or maximum tolerated dose after dose escalation from 1 tablet
干预措施: Candesartan (Drug)
结局指标
主要结局
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
时间窗: 3 years
次要结局
- 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)
- 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)
- Proportion of treatment discontinuations in the candesartan and placebo groups.(3 years)
研究者
Cristina Avendaño Solá
Head of Clinical Pharmacology Department
Puerta de Hierro University Hospital