HERMES: Effects of ziltivekimab versus placebo on morbidity and mortality in patients with heartfailure with mildly reduced or preserved ejection fraction and systemic inflammation.
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 5,600
- 试验地点
- 39
- 主要终点
- To demonstrate the superiority of
研究概览
简要总结
This study will be do to see if ziltivekimab can be used to treat people with heart failure and inflamation. Participants will either get ziltivekimab or placebo.This is an interventional, randomised, parallel-group, double-blind, placebo-controlled, multicentre, multi-national cardiovascular outcomes trial (CVOT) designed to evaluate the effects of ziltivekimab 15 mg versus placebo (randomised 1:1), both administered s.c. once-monthly and added to standard of care, on morbidity and mortality of participants with heart failure (HF) with mildly reduced ejection fraction (HFmrEF) or HF with preserved ejection fraction (HFpEF) and systemic inflammation.
The study consists of 3 periods: a screening period (up to 5 weeks), a treatment period and a 3- month follow-up period after the end of treatment visit. Eligible participants will be randomly assigned to study intervention prior to initiation of the treatment period. This study is expected to last for upto four years. Participants will have upto 20 clinic visits. Participants will have to use a study app in their phone to record and share information about all their injections of their study medicine and their questionaires.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant, Investigator and Outcome Assessor Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 92.00 Year(s)（—）
- 性别
- All
入选标准
- •1 Serum highsensitivity Creactive protein hsCRP greater than equal to 2 milligrams per liter mgL at screening visit 1 Disease specific cardiovascular 2 At least one of the following a Nterminalprobrain natriuretic peptide NTproBNP greater than equal to 300 picograms per milliliter pgmL at screening Visit 1 for patients without ongoing atrial fibrillationflutter If ongoing atrial fibrillationflutter at screening visit 1 NTproBNP must be greater than equal to 600 pgmL Note that the screening electrocardiogram ECG must be obtained the same day as sampling for NTproBNP b Hospitalisation or urgentunplanned visit with a primary diagnosis of decompensated heart failure which required intravenous loop diuretic treatment within the last 9 months prior to screening visit 1 in combination with NTproBNP greater than equal to 200 pgmL at screening Visit 1 for patients without ongoing atrial fibrillationflutter If ongoing atrial fibrillationflutter at screening visit 1 NTproBNP must be greater than equal to 600 pgmL 3 Diagnosis of heart failure New York Heart Association classification NYHA Class IIIV 4 Left ventricular ejection fraction LVEF greater than 40 percentage documented by echocardiography within 12 months prior to or at screening visit 1 The LVEF must be documented in medical records and the most recent measurement must be used to determine eligibility with no interim event signalling potential deterioration in ejection fraction eg myocardial infarction MI or heart failure HF hospitalisation 5 Structural heart disease andor functional heart disease documented by echocardiography within 12 months prior to or at screening visit 1 showing at least one of the following 6 Left atrial LA volume index greater than 34 milliliter per meter square mLm2 7 LA diameter greater than equal to 38 centimeter cm 8 LA length greater than equal to 50 cm 9 LA area greater than equal to 20 cm square 10 LA volume greater than equal to 55 milliters mL 11 Intraventricular septal thickness greater than equal to 11 cm 12 Posterior wall thickness greater than equal to 11 cm 13 Left ventricular LV mass index greater than equal to 115 grams per meter square gm2 in men or greater than equal to 95 gm2 in women 14 Ee mean septal and lateral greater than equal to 10 15 e mean septal and lateral less than 9 centimeter per second cms 16 No heart failure hospitalisations or urgent heart failure visits between screening visit 1 and randomisation visit 2.
排除标准
- •Medical conditions cardiovascular 1 Myocardial infarction stroke unstable angina pectoris transient ischaemic attack or heart failure hospitalisation within 30 days prior to screening visit 1 2 Systolic blood pressure greater than equal to 180 millimeters of mercury mmHg at screening visit 1 If the systolic blood pressure is 160179 mmHg the patient should be receiving greater than equal to 3 antihypertensive drugs Note Potential participants may be retested for this criterion within the visit window and without rescreening at the discretion of the investigator 3 Heart rate above 110 or below 40 beats per minute as evaluated on the electrocardiogram ECG performed at screening visit 1 Note Potential participants may be retested for this criterion within the visit window and without rescreening at the discretion of the investigator 4 Planned coronary carotid or peripheral artery revascularisation known during the screening period visit 1 Note Planned coronary angiogram is not exclusionary Planned cardiac device or atrial flutteratrial fibrillation ablation procedure known during the screening period visit 1 5 Major cardiac surgical noncardiac surgical or major endoscopic procedure thoracoscopic or laparoscopic within the past 60 days prior to randomisation visit 2 or any major surgical procedure planned at the time of randomisation visit 2 6 Heart failure due to infiltrative cardiomyopathy eg sarcoid amyloid arrhythmogenic right ventricular cardiomyopathy Takutsubo cardiomyopathy genetic hypertrophic cardiomyopathy or obstructive cardiomyopathy active myocarditis constrictive pericarditis cardiac tamponade uncorrected more than moderate primary valve disease 7 Primary pulmonary hypertension chronic pulmonary embolism severe pulmonary disease including COPD 8 Any other condition judged by the investigator that could account for heart failure symptoms and signs eg anaemia hypothyroidism Medical conditions infectionsimmunosuppression Clinical evidence of or suspicion of active infection at the discretion of the investigator.
结局指标
主要结局
To demonstrate the superiority of
时间窗: at 48 Months
ziltivekimab 15 mg s.c. once-monthly
时间窗: at 48 Months
versus placebo, both added to standard
时间窗: at 48 Months
of care, in reducing the risk of CV
时间窗: at 48 Months
death and HF events in participants
时间窗: at 48 Months
with HFmrEF or HFpEF and systemic
时间窗: at 48 Months
inflammation.
时间窗: at 48 Months
次要结局
- To demonstrate the superiority of(ziltivekimab 15 mg s.c. once-monthly)
- Number of CV deaths, HF(hospitalisations or urgent HF visits)