Lokelma for Maximisation of RAAS Inhibition in CKD Patients With Heart Failure; Randomised.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 112
- 试验地点
- 2
- 主要终点
- Number of participants who achieve the maximum dose
研究概览
简要总结
Background: CKD in patients with heart failure (HF) is common and associated with poor prognosis. Despite evidence of benefit with Renin-Angiotensin-Aldosterone-System inhibitor (RAASi) agents, they are avoided due to fear of hyperkalaemia. New potassium binders, e.g. Sodium Zirconium Cyclosilicate (SZC), reduce incidence of hyperkalaemia in CKD-HF patients and hence may help RAASi maximisation, which has not been investigated in an RCT.
Purpose: The proposed study will randomise HFrEF patients with stable CKD 3-5 and serum potassium 5-5.0 mmol/L, to receive SZC or placebo while RAASi therapy is maximised. The aim of the study is to examine if SZC is superior to placebo in achieving maximal doses of ACEi/ARB, e.g. Ramipril 10 mg, Candesartan 32 mg; and mineralocorticoid receptor antagonist, e.g. Epleronone 50 mg or Spironolactone 50 mg, avoiding hyperkalaemia.
Methods: Eligible patients with eGFR<60 mL/min/1.73m2, heart failure (EF<40%) on none/submaximal dose of RAASi will be randomised to receive 10g TDS of investigational medicinal product (IMP), either SZC or placebo, for 48 hours and in 10 or 5g OD guided by laboratory serum potassium (K+). Every two weeks the RAASi dose will be increased and IMP adjusted according to a strict protocol and guided by laboratory potassium and creatinine. The primary endpoint of the study is achievement of maximal dose of RAASi in randomised patients avoiding hyperkalaemia, i.e. K+≤5.6 mmol/L. Patients will be allowed to continue with RAASi maximisation to K+<6.0mmol/L. Patients will be tested at baseline and follow-up visits for hyperkalaemia, AKI, symptomatic hypotension and QT prolongation on ECG.
Results: The study results will show if SZC is superior to placebo for RAASi maximisation in CKD-HF patients while maintaining safe levels of serum potassium without any adverse impact on quality of life. The study will demonstrate if SZC allows higher RAASi dose and more dose escalations than placebo. It will also examine the impact of RAASi escalation on creatinine, proteinuria, and cardiac blood biomarkers.
Conclusion: If positive, the results of this study will demonstrate that SZC enables RAASi up titration in CKD-HF patients, which potentially can help achieve optimal treatment and improve quality of life of the patient.
详细描述
Title Lokelma for maximisation of RAAS inhibition in CKD patients with Heart Failure; RCT (LiFT) Clinical Phase Phase III Trial Design Double-Blind, Placebo-Controlled, Randomised Trial Participant Population Patients with systolic heart failure chronic kidney disease 3-5 and no/submaximal RAASi
Inclusion.Criteria: :
- Age >18 years
- Heart failure, clinical or echo confirmed (HFrEF); patients with AF will be included provided the EF can be determined
- NYHA class II to IV
- Serum potassium 5.0-5.5 mmol/L
- Adequate blood pressure (>90 mm Hg systolic and without postural hypotension; drop of Systolic Blood Pressure >20 or feeling dizzy with change in posture; exclude patients with symptomatic hypotension due to high doses of ACEi/ARB or MRA unless the clinical condition has improved)
- CKD with stable eGFR <60 ml/min/1.73m2
- None or submaximal dose of ACEi/ARB and/or MRA or both
Exclusion:
- Pregnancy
- Active malignancy or infection
- BMI>35 kg/m2
- Poorly controlled sugar HBA1C> 70 mmol/mmol
- Recent ACS
- Potassium therapy
- Prolonged QT>550msec, congenital QT syndrome and history of prolong QT requiring drug discontinuation Planned Sample Size/Target 130 patients
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Placebo
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
- •Age >18 years
- •Heart failure, clinical or echo confirmed (HFrEF); patients with AF will be included provided the EF can be determined
- •NYHA class II to IV
- •Serum potassium 5.0-5.5 mmol/L
- •Adequate blood pressure (>90 mm Hg systolic and without postural hypotension; drop of Systolic Blood Pressure >20 or feeling dizzy with change in posture; exclude patients with symptomatic hypotension due to high doses of ACEi/ARB or MRA unless the clinical condition has improved)
- •CKD with stable eGFR <60 ml/min/1.73m2
- •None or submaximal dose of ACEi/ARB and/or MRA or both
排除标准
- •• Pregnancy
- •Active malignancy or infection
- •BMI>35 kg/m2
- •Poorly controlled sugar HBA1C> 70 mmol/mmol
- •Recent ACS
- •Potassium therapy
- •Prolonged QT>550msec, congenital QT syndrome and history of prolong QT requiring drug discontinuation
研究组 & 干预措施
Lokelma
Lokelma therapy
干预措施: Lokelma Oral Product (Drug)
Control
Placebo
干预措施: Lokelma Oral Product (Drug)
结局指标
主要结局
Number of participants who achieve the maximum dose
时间窗: 16 weeks
Ramipril 5 mg OD + Spironolactone 25 mg OD for patients on a baseline RAASi dose that is less than Ramipril 5 mg OD + Spironolactone 25 mg OD or equivalent Ramipril 10 mg OD + Spironolactone 50 mg OD for patients on a baseline RAASi dose that is more or equal than Ramipril 5 mg OD + Spironolactone 25 mg OD or equivalent
次要结局
- Number of participants achieving other outcomes(16 weeks)