OPtimizing Aldosterone Receptor Antagonist Therapy by Sodium Zirconium Cyclosilicate in Heart Failure (OPRA-HF)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 1
- 试验地点
- 5
- 主要终点
- To demonstrate the efficacy of Sodium Zirconium Cyclosilicate (SZC) on optimizing MRA in HFrEF, SZC vs Placebo. The efficacy will be assessed by difference in the proportion of patients who may or may not maintain MRA at a dose ≥ 25 mg daily or a dose increase by 25 mg daily and K level in the normal range (3.5-5.0 mmol/L) at the end of study, without rescue therapy due to hy-perkalemia at any point during the randomization phase.
研究概览
简要总结
To demonstrate the efficacy and safety of Sodium Zirconium Cyclosilicate (SZC) in optimizing mineralocorticoid receptor antagonists (MRA) in symptomatic patients with heart failure with reduced ejection fraction (HFrEF)
研究设计
- 分配方式
- Randomized
- 主要目的
- Optimizing Aldosterone Receptor Antagonist Therapy By Szc In Heart Failuure (opra-hf)
- 盲法
- Double (Investigator, Analyst, Monitor, Carer)
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Obtain signed informed consent prior to any study specific procedures.
- •>18 yrs, irrespective of sex.
- •LVEF ≤ 40%, with echocardiography within last 2 years including those with recovered EF later on
- •NYHA II-IV.
- •Stable heart failure as judged by local Investigator. Patients may be enrolled as an outpatient or in-hospital at, or close to, the time of hospital discharge.
- •On optimal treatment including ACE/ARB/ARNI, beta blockers, SGLT2 inhibitor as per physician´s judgement.
- •Suboptimal treatment with MRA (defined as: no use or ≤ 25 mg daily).
- •AND one of followings: a. Prior hyperkalemia (S-K> 5.0 mmol/L or P-K> 4.8 mmol/L) during MRA treatment within last 24 months, and current S-K ≤ 5.0 or P-K ≤ 4.8 mmol/L b. Current S-K 4.5-5.0 mmol/L or P-K 4.3-4.8 mmol/L and potential risk of hyperkalemia as indicated by eGFR 30-45 ml/min/1,73 m2 (modi-fied MDRD formula) c. Current S-K 5.1-5.9 mmol/L or P-K 4.9-5.7 mmol/L
排除标准
- •Symptomatic hypotension (< 90/60 mmHg)
- •Symptomatic and uncontrolled atrial fibrillation despite treatment, or asymp-tomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted
- •QTc(f) > 550 msec
- •Currently pregnant (confirmed with positive pregnancy test) or planned pregnancy or breast-feeding
- •Can not sign informed consent
- •eGFR < 30 ml/min/1,73 m2 (modified MDRD formula)
- •HF due to restrictive cardiomyopathy, hypertrophic (obstructive) cardiomy-opathy or primary valvular disease
- •Current/recent (within 3 months) hospitalization due to myocardial infarc-tion, unstable angina pectoris, coronary revascularization (percutaneous cor-onary intervention or coronary artery bypass grafting), or other interventions (valvular repair/replacement, cardiac transplantation, or implantation of a ventricular assistance device)
- •Ongoing or planned dialysis
- •Prior history of hypersensitivity (other than hyperkalemia) to MRA or SZC
- •Advanced malignancy requiring treatment
- •History of QT prolongation associated with other medication which required discontinuation of that medication
- •Congenital long QT syndrome
结局指标
主要结局
To demonstrate the efficacy of Sodium Zirconium Cyclosilicate (SZC) on optimizing MRA in HFrEF, SZC vs Placebo. The efficacy will be assessed by difference in the proportion of patients who may or may not maintain MRA at a dose ≥ 25 mg daily or a dose increase by 25 mg daily and K level in the normal range (3.5-5.0 mmol/L) at the end of study, without rescue therapy due to hy-perkalemia at any point during the randomization phase.
To demonstrate the efficacy of Sodium Zirconium Cyclosilicate (SZC) on optimizing MRA in HFrEF, SZC vs Placebo. The efficacy will be assessed by difference in the proportion of patients who may or may not maintain MRA at a dose ≥ 25 mg daily or a dose increase by 25 mg daily and K level in the normal range (3.5-5.0 mmol/L) at the end of study, without rescue therapy due to hy-perkalemia at any point during the randomization phase.
次要结局
- To determine the efficacy of SZC when compared to placebo in maintaining achieved MRA-dose after run-in period, SZC vs Placebo.
- To determine the impact of MRA-optimization by SZC in QoL-parameters, SZC vs Place-bo.
- To determine the estimated treatment persistency of highest tolerable dose (25-50 mg dai-ly) of MRA between SZC vs Placebo.
- To evaluate the safety and tolerability of SZC when compared to placebo as assessed by differences in percent (%) between the two groups in pre-specified safety endpoints (oc-curring at any point during the study)
研究者
Michael
Scientific
Vaestra Goetalandsregionen