Swedish Cardiac And Renal Failure Study-1 (SCARF-1): An Open-Label Pilot Trial to Evaluate the Feasibility, Safety and Efficacy of Eplerenone in Patients With Heart Failure With Reduced Ejection Fraction and Severe Chronic Kidney Disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- The primary endpoint is the proportion of participants who complete the treatment period with and without the need to use a potassium binder
研究概览
简要总结
Previous studies have shown that patients with heart failure with reduced pumping function and preserved kidney function experience improved symptoms, longer survival, and fewer hospitalizations when treated with medications such as eplerenone. However, individuals with impaired kidney function have been excluded from these trials due to concerns about potential adverse effects on potassium levels, kidney function, and possibly also blood pressure. As a result, clear treatment recommendations for this high-risk group are lacking.
In recent years, however, background therapies have been modernized and are now associated with a lower risk of potassium disturbances. Preliminary data also suggest that patients with impaired kidney function may benefit from eplerenone treatment. However, confirmation through dedicated studies is needed.
The primary objective of this pilot trial is to assess the feasibility and safety of eplerenone in patients with heart failure with reduced pumping function and impaired kidney function. Treatment effectiveness will also be explored.
详细描述
Virtually all major trials in heart failure with reduced ejection fraction (HFrEF), including those investigating mineralocorticoid receptor antagonists (MRAs) such as eplerenone, have excluded patients with severe chronic kidney disease (CKD). This exclusion has likely been driven by concerns over the risks of hyperkalemia and worsening renal function (WRF). However, post-hoc analyses of these major trials, along with data from registries and cohort studies, suggest that patients with more advanced renal impairment may still derive an overall benefit from MRA treatment.
The objective of this pilot trial is to evaluate the feasibility and safety of eplerenone in patients with HFrEF and severe CKD. An exploratory analysis of efficacy will also be performed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Transthoracic Echocardiography (TTE) analysis will take place retrospectively in a blinded manner
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The participant has given their written consent to participate
- •A diagnosis of HFrEF according to current criteria, for at least three months before the screening visit
- •Echocardiography within 24 months of the screening visit with ejection fraction ≤ 40%. The responsible investigator is allowed to order a new TTE at their own discretion if clinically indicated - e.g. following the initiation of markedly intensified HFrEF-treatment or in the event of significant clinical deterioration. If the new TTE shows an EF > 40%, the participant will not be eligible for inclusion. However, a potential echocardiographic worsening should not, by itself, preclude enrollment
- •New York Heart Association class II-III
- •Optimally treated and stable HFrEF (according to the investigator) since at least four weeks before the screening visit. Treatment should include beta-blockers, sodium/glucose co-transporter 2 inhibitors, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers if eGFR ≥ 20 ml/min/1.73m2 according to the revised Lund-Malmö method. Participants should also have cardiac resynchronization therapy or an implantable cardioverter-defibrillator if the indication exists according to current guidelines
- •eGFR < 30 ml/min/1.73m2 according to the revised Lund-Malmö method at least once during the 12 months before the screening visit, and eGFR < 45 ml/min/1.73m2 at the time of inclusion
排除标准
- •P-K ≥ 5.6
- •For the first ten study participants:
- •eGFR < 20 ml/min/1.73m2 according to the revised Lund-Malmö method, or projected decline in eGFR to < 10 ml/min/1.73m2 during the 36-week study period. The projected decline will be estimated using the three most recent eGFR values from the previous 6-12 months
- •- For the remainder of the study participants: eGFR < 10 ml/min/1.73m2 according to the revised Lund-Malmö method, or projected decline in eGFR to < 10 ml/min/1.73m2 during the 36-week study period. The projected decline will be estimated using the three most recent eGFR values from the previous 6-12 months
- •Ongoing/planned dialysis
- •Systolic blood pressure < 90 mmHg
- •Uncontrolled hypertension as judged by the investigator
- •Severe hepatic impairment (Child-Pugh C)
- •History of, or planned, heart transplantation or left ventricular assist device
- •Unwillingness to comply with highly effective contraceptive methods, or ongoing/planned pregnancy, or breastfeeding
- •Previous allergic reaction to an MRA or a potassium binder
- •Ongoing treatment with lithium, cyclosporine, tacrolimus, nonsteroidal anti-inflammatory drugs, trimethoprim, or strong CYP3A inhibitors (ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin, telithromycin, and nefazodone) or inducers (rifampicin, carbamazepine, phenytoin, phenobarbital, and St. John's Wort)
- •QTc(f) ≥ 550 msec, history of QT prolongation associated with any medication requiring medication discontinuation, or congenital long QT syndrome
- •Uncontrolled arrhythmia as judged by the investigator
- •Acute cardiac hospitalization or procedure within four weeks before inclusion
- •Not suitable as judged by the investigator (presumed inability to participate, severe or terminal co-morbidity, and expected survival < 12 months)
- •Previously enrolled in this trial or participation in another trial not approved for co-enrollment
研究组 & 干预措施
Single-arm
Eplerenone
干预措施: Eplerenone (Drug)
结局指标
主要结局
The primary endpoint is the proportion of participants who complete the treatment period with and without the need to use a potassium binder
时间窗: Between the first and final day of the 12-week eplerenone treatment period
Without eplerenone interruption/discontinuation due to safety reasons, with and without SZC
次要结局
- The occurrence of plasma potassium (P-K) ≥ 5.6 and ≥ 6.0(Between the first and final day of each of the three 12-week study periods)
- Hospitalization for hyperkalemia(Between the first and final day of each of the three 12-week study periods)
- The occurrence of P-K < 3.0(Between the first and final day of each of the three 12-week study periods)
- Hospitalization for hypokalemia(Between the first and final day of each of the three 12-week study periods)
- Decrease in eGFR of ≥ 30% and ≥ 50%(Between the first and final day of each of the three 12-week study periods)
- Hospitalization for renal failure(Between the first and final day of each of the three 12-week study periods)
- Initiation of dialysis(Between the first and final day of each of the three 12-week study periods)
- Participant-reported lightheadedness due to orthostatic hypotension as judged by the investigator(Between the first and final day of each of the three 12-week study periods)
- Participant-reported syncope(Between the first and final day of each of the three 12-week study periods)
- Any participant-reported side effect(Between the first and final day of each of the three 12-week study periods)
- Hospitalization for heart failure(Between the first and final day of each of the three 12-week study periods)
- All-cause hospitalization(Between the first and final day of each of the three 12-week study periods)
- Cardiovascular death(Between the first and final day of each of the three 12-week study periods)
- All-cause death(Between the first and final day of each of the three 12-week study periods)
研究者
Carl Haggård
MD, PhD
Karolinska Institutet