LIFT 试验：一项双盲、随机、安慰剂对照试验的研究方案，旨在评估 K-binder Lokelma 在合并心力衰竭的慢性肾脏病患者中最大化肾素-血管紧张素-醛固酮系统抑制的效果。
The LIFT trial: study protocol for a double-blind, randomised, placebo-controlled trial of K-binder Lokelma for maximisation of RAAS inhibition in CKD patients with heart failure.
机构信息
St George's University Hospitals NHS Foundation Trust, London, UK.
St George's, University of London, Cranmer Terrace, London, SW17 0RE, UK.
出版信息
BMC Nephrol. 2021 Jul 6;22(1):254. doi: 10.1186/s12882-021-02439-2.
BACKGROUND
CKD is common in heart failure (HF) and associated with morbidity and mortality, yet life-prolonging medications such as renin-angiotensin-aldosterone inhibitors (RAASi) are underused due to risk of hyperkalaemia. Sodium zirconium cyclosilicate (SZC) is a potassium-binding medication that has been shown to reduce incidence of hyperkalaemia in CKD, non-CKD, and HF populations, which we propose will support maximisation of RAASi therapy.
METHODS
We propose a 1:1 randomised, double-blind, placebo-controlled trial in which participants will receive either SZC or placebo. We will up-titrate participants' RAASi therapy while monitoring their serum potassium levels and adjusting their SZC dose if necessary. Participants with CKD and HF will be recruited from CKD and HF clinics at St George's Hospital. The total study period will be 18 months; 130 participants will be enrolled for approximately two months each following screening. Our primary outcome will be the proportion of participants who achieve maximum RAASi dose while maintaining normokalaemia. Secondary outcomes include participants reaching maximum RAASi dose without severe hyperkalaemia; time from randomisation to hyperkalaemia; time from randomisation to severe hyperkalaemia; number of RAASi dose escalations per participant; final doses of RAASi therapy; changes in quality of life score, eGFR, ACR, serum sodium, troponin T; number and duration of hospital admissions; and within-participant change in serum potassium compared to baseline.
DISCUSSION
This trial will be the first to examine the use of SZC for the maximisation of RAASi dosing in patients with advanced CKD and HF. We will assess the impact of achieving target RAASi dosing on hospital admission rates and duration of stay, with the hope that optimum RAASi treatment will translate into reduced morbidity and improved QoL. If clinical benefit is demonstrated, we hope that the joint multidisciplinary CKD-HF approach will be expanded.
TRIAL REGISTRATION
EudraCT number 2020-002946-18. Registered on 08 June 2020. Online record pending.
背景
慢性肾脏病（CKD）在心力衰竭（HF）中很常见，并且与发病率和死亡率相关，但是由于高钾血症的风险，延长生命的药物，如肾素-血管紧张素-醛固酮抑制剂（RAASi）的使用不足。硅酸锆钠（SZC）是一种钾结合药物，已证明可降低 CKD、非 CKD 和 HF 人群的高钾血症发生率，我们认为这将支持最大限度地使用 RAASi 治疗。
方法
我们提出了一项 1:1 随机、双盲、安慰剂对照试验，参与者将接受 SZC 或安慰剂。我们将在监测血清钾水平的同时逐步增加参与者的 RAASi 治疗，并在必要时调整 SZC 剂量。CKD 和 HF 患者将从圣乔治医院的 CKD 和 HF 诊所招募。总研究期为 18 个月；筛选后，将招募约 130 名参与者，每个参与者的研究时间约为两个月。我们的主要结局是在保持血钾正常的情况下达到最大 RAASi 剂量的参与者比例。次要结局包括达到最大 RAASi 剂量而无严重高钾血症的参与者比例；从随机分组到高钾血症的时间；从随机分组到严重高钾血症的时间；每个参与者的 RAASi 剂量升级次数；RAASi 治疗的最终剂量；生活质量评分、eGFR、ACR、血清钠、肌钙蛋白 T 的变化；住院人数和住院时间；与基线相比，血清钾的个体内变化。
讨论
这将是第一项研究 SZC 在 CKD 和 HF 晚期患者中最大化 RAASi 剂量的使用的试验。我们将评估达到目标 RAASi 剂量对住院率和住院时间的影响，希望最佳 RAASi 治疗能降低发病率并提高 QoL。如果临床获益得到证实，我们希望联合多学科的 CKD-HF 方法能够得到扩展。
试验注册
EudraCT 编号 2020-002946-18。于 2020 年 6 月 8 日注册。在线记录待批。
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