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

Abstract

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.

Optimization of RAASi Therapy with New Potassium Binders for Patients with Heart Failure and Hyperkalemia: Rapid Review and Meta-Analysis

“…The evidence for the effect of Patiromer on outcomes had high certainty and is in accordance with the effect in patients with HK without HF. The evidence for ZSC had low certainty, and future studies, such as the LIFT study [ 36 ], may change the results.…”

Chronic Kidney Disease: Role of Diet for a Reduction in the Severity of the Disease

“…The true benefit of potassium restriction in CKD is not clear, considering that a diet with a high content of potassium-rich foods, such as plant-based low-protein diets, can be as beneficial on the prognosis. Potassium levels in serum can further be improved using the new K-binders, whose benefits and efficacy are shown in randomized control trials [ 78 , 79 ], allowing implementing plant-based low-protein diets with lower risk of hyperkalemia. Further research investigating the effect of a low-potassium diet and the progression of renal disease are required.…”

“…Further research investigating the effect of a low-potassium diet and the progression of renal disease are required. It is unclear whether a potassium-restricted diet can slow CKD progression; however, research shows that it may reduce all-cause mortality in CKD [ 79 ].…”

Mediterranean Diet Adherence and Nutritional Status in Dalmatian Diabetic Hypertensive Patients Regarding Presence of Chronic Kidney Disease—Is There Any Difference?

“…It has been noticed that CKD patients often avoid nut consumption because of their high potassium content, which in turn can lead to hyperkalemia [ 53 ]. Serum potassium levels can further be lowered by proper food preparation and using potassium binders that lower the risk of food-induced hyperkalemia [ 54 , 55 ].…”