CTRI/2025/12/099785尚未招募3 期
EASi-HF reduced – A Phase III double-blind, randomised, parallel-group superiority trial to evaluate efficacy and safety of the combined use of oral vicadrostat (BI 690517) and empagliflozin compared with placebo and empagliflozin in participants with symptomatic chronic heart failure (HF: NYHA II-IV) and left ventricular ejection fraction (LVEF) less than 40 percent
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 4,200
- 试验地点
- 15
- 主要终点
- Time to first event of:
研究概览
简要总结
Regardless of recent treatment advances in the management of HF, the residual risk for cardiovascular death, hospitalisation for heart failure and impaired quality of life remains substantial in patients with HF, which is applicable also to patients with LVEF less than 40 percent. The combination of vicadrostat and empagliflozin may achieve an additive or synergistic beneficial effect on HF outcomes. Therefore, the aim of this trial is to investigate the efficacy and safety of the combined use of vicadrostat and empagliflozin compared with placebo and empagliflozin in participants with symptomatic heart failure (HF: NYHA II-IV) and LVEF less than 40 percent.
研究设计
- 研究类型
- Interventional
- 分配方式
- Other
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Eligible participants will have a diagnosis of HF with LVEF less than 40 percent and meet eligibility criteria below
- •At least 18 years old and at least at the legal age of consent in countries where it is greater than 18 years
- •Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
- •Male or female participants.
- •Women of childbearing potential (WOCBP) 1 must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1 percent per year when used consistently and correctly.
- •A list of contraception methods meeting these criteria and instructions on the duration of their use is provided in Section 4.2.2.
- •Chronic HF diagnosed at least 3 months before Visit 1, and in NYHA classes II to IV at Visit 1, with LVEF less than 40 percent per local reading (obtained by echocardiography, radionuclide ventriculography, invasive angiography, MRI, or CT).
- •A historical LVEF may be used if it was measured within 12 months prior to Visit 1, or the LVEF may be measured after study consent has been obtained and before randomisation at Visit 2 (if several LVEF assessments are available, the most recent one should be considered).
- •Additional inclusion criteria apply to the optional rhythm monitoring substudy:
- •Willing and able to provide informed consent for substudy participation
- •Sinus rhythm on Visit 1 ECG.
排除标准
- •Treatment with an MRA (e.g. spironolactone, eplerenone, finerenone) within 14 days prior to Visit 1 or requiring such treatment before randomisation or planned during the trial based on the judgment of the investigator.
- •Treatment with an MRA should not be discontinued with the intention of study enrolment.
- •Treatment with amiloride or other potassium-sparing diuretic within 14 days prior to Visit 1 or requiring such treatment before randomisation or planned during the trial based on the judgment of the investigator.
- •Receiving the following treatments: • A direct renin inhibitor (e.g. aliskiren) at Visit 2 • More than one ACEi, ARB or ARNi used simultaneously at Visit 2 • Other aldosterone synthase inhibitors, e.g. baxdrostat at Visit 2 or planned during the trial • Systemic mineralocorticoid replacement therapy (e.g. fludrocortisone) at Visit 2 • In case of acute decompensated HF: o i.v. inotrope, i.v. vasodilating drug (e.g. nitrate, nitroprusside), or i.v. natriuretic peptide (e.g. nesiritide, carperitide), or mechanical support (e.g. intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, any ventricular assist device) within 24 hours prior to randomisation o i.v. diuretic with a dose that has been increased/intensified within 6 hours prior to randomisation (a stable dose of an i.v. diuretic is not exclusionary)
- •MI, TIA, stroke, coronary artery bypass graft surgery (CABG), heart valve surgery per intervention or any other major surgery (major according to the investigators assessment) within 90 days prior to Visit 2, or scheduled for major elective surgery (e.g. hip replacement, CABG)
- •Percutaneous coronary intervention (PCI) or any angiography using iodinated contrast agents in the 7 days prior to Visit 2
- •Heart transplant recipient, awaiting heart transplant, or currently implanted LVAD
- •Known cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), accumulation diseases (e.g. haemochromatosis, Fabry disease), muscular dystrophies, hypertrophic obstructive cardiomyopathy or known pericardial constriction, or cardiomyopathy with potentially reversible cause such as stress or peripartum cardiomyopathy or cardiomyopathy induced by chemotherapy within 12 months prior to Visit 1 and until Visit 2
- •Acute inflammatory heart disease, such as acute myocarditis, within 90 days preceding prior to Visit 1 and until Visit 2
- •Known severe valvular heart disease (obstructive or regurgitant) except mitral regurgitation secondary to left ventricular dilatation, as per investigators judgement, or valvular heart disease scheduled for surgical or invasive procedures at Visit 1, or anticipated invasive treatment during the study
- •Atrial fibrillation or Atrial flutter with a resting pulse rate more than equals to 110 bpm documented by ECG at Visit 2
- •Clinically relevant ventricular arrhythmia neither treated medically nor with a device with a defibrillator function at Visit 1 and per or Visit 2
- •Unless managed with an implanted pacemaker: symptomatic bradycardia, sick sinus syndrome, Mobitz Type II second-degree AV block, or third-degree heart block
- •Implantation of CRT device within 3 months prior to Visit 1 or until Visit 2, or scheduled for a CRT device implantation.
- •Symptomatic hypotension and per or a SBP less than 100 mmHg at Visit 1 or Visit 2
- •SBP more than equals to 180 mmHg at Visit 1 or Visit
- •If SBP more than 150 mmHg and less than 180 mmHg at Visit 1, the participant should be receiving at least 3 antihypertensive drugs.
- •Severe chronic pulmonary disease according to investigators judgement, e.g. with known FEV1 less than 50 percent or need for home oxygen for pulmonary disease, pulmonary arterial hypertension, Chronic Thromboembolic Pulmonary Hypertension (CTEPH), or chronic obstructive pulmonary disease (COPD) exacerbation requiring i.v. or chronic oral steroids within 3 months prior to Visit 1 or until Visit 2
- •Serum potassium3 more than 5.2 mmol per L measured by the central laboratory at Visit 1 (Note: one reassessment of serum potassium is allowed during screening)
- •ALT or AST3 more than 3x ULN at Visit 1 or known hepatic cirrhosis (Child Pugh C), or other liver disease causing severe impaired liver function, according to investigator’s judgement
- •Impaired renal function, defined as eGFR3 less than 20 mL/min/1.73 m2 (CKD-EPI) as determined at Visit 1 by the central laboratory or on renal replacement therapy (Note: one reassessment of eGFR is allowed during screening)
- •Haemoglobin (Hb)3 less than 9 g per dL as determined at Visit 1 by the central laboratory.
- •Known adrenal insufficiency (e.g. Addison disease) or Cushings syndrome
- •History of ketoacidosis within 5 years prior to Visit 1 or until Visit 2
- •Gastrointestinal surgery or gastrointestinal disorder that could interfere with trial medication absorption in the investigators opinion, e.g. intestinal resection, inflammatory bowel disease, currently active gastritis, pancreatitis
- •Type 1 diabetes mellitus, or history of other autoimmune causes of diabetes mellitus (e.g. LADA)
- •Any documented active or suspected malignancy or history of malignancy within 5 years prior to Visit 1, except appropriately treated basal cell carcinoma of the skin, in situ carcinoma of uterine cervix or low risk prostate cancer (participants with pretreatment PSA less than 10 ng per mL and biopsy Gleason score of less than equals to 6 and clinical stage T1c or T2a)
- •Participants who must or wish to continue the intake of restricted medications (see Section 4.2.2.1) or any drug considered likely to interfere with the safe conduct of the trial.
- •Currently enrolled in another investigational device or drug trial, or less than 30 days or 5 half-lives of the investigational drug (whichever is longer) since ending another investigational device or drug trial(s) or receiving other investigational treatment(s).
- •Those patients participating in a purely observational trial will not be excluded.
- •Chronic alcohol or drug abuse or any condition that, in the investigators opinion, makes them an unreliable trial participant or unlikely to complete the trial
- •Intolerance or known allergy or hypersensitivity to vicadrostat or empagliflozin or other SGLT2 inhibitors and per or any of the excipients (including lactose).
- •A list of ingredients of vicadrostat and empagliflozin and placebo is provided in the ISF
- •Any condition not covered by any of the other exclusion criteria, including abnormal laboratory values, which in the investigators opinion, might make a participant otherwise vulnerable (e.g. participant in custody by order of an authority or a court) or jeopardise patient safety or compliance with the protocol.
- •Additional exclusion criteria apply to the optional rhythm monitoring substudy:
- •Known allergies, intolerance or hypersensitivities to adhesives or hydrogel
- •Cardiac pacemaker, ICD, or CRT device
- •History of permanent atrial fibrillation or atrial flutter.
结局指标
主要结局
Time to first event of:
时间窗: week 32 and week 52
1)Hospitalization due to heart failure (HHF)
时间窗: week 32 and week 52
2)Cardiovascular (CV) death
时间窗: week 32 and week 52
3)Urgent heart failure (HF) visit event of CV death, hospitalization for heart failure (HHF) or urgent HF visit in participants with HF and LVEF less than 40 percent not taking MRA.
时间窗: week 32 and week 52
次要结局
- Absolute change from baseline in Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) at Week 32(Time to all-cause mortality.)
研究者
研究点 (15)
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