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 medica...
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| Format: | Article |
| Language: | English |
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BMC
2021-07-01
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| Series: | BMC Nephrology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12882-021-02439-2 |
| _version_ | 1818872244591394816 |
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| author | Daniel Murphy Irina Chis Ster Juan-Carlos Kaski Lisa Anderson Debasish Banerjee |
| author_facet | Daniel Murphy Irina Chis Ster Juan-Carlos Kaski Lisa Anderson Debasish Banerjee |
| author_sort | Daniel Murphy |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T12:35:44Z |
| format | Article |
| id | doaj.art-1ab9deeb047f4fc59bd5f4c5f21e0f4c |
| institution | Directory Open Access Journal |
| issn | 1471-2369 |
| language | English |
| last_indexed | 2024-12-19T12:35:44Z |
| publishDate | 2021-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Nephrology |
| spelling | doaj.art-1ab9deeb047f4fc59bd5f4c5f21e0f4c2022-12-21T20:21:10ZengBMCBMC Nephrology1471-23692021-07-012211910.1186/s12882-021-02439-2The 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 failureDaniel Murphy0Irina Chis Ster1Juan-Carlos Kaski2Lisa Anderson3Debasish Banerjee4St George’s University Hospitals NHS Foundation TrustSt George’s, University of LondonSt George’s, University of LondonSt George’s University Hospitals NHS Foundation TrustSt George’s University Hospitals NHS Foundation TrustAbstract 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.https://doi.org/10.1186/s12882-021-02439-2Chronic kidney diseaseHeart failureRAASPotassium binderRandomised |
| spellingShingle | Daniel Murphy Irina Chis Ster Juan-Carlos Kaski Lisa Anderson Debasish Banerjee 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 BMC Nephrology Chronic kidney disease Heart failure RAAS Potassium binder Randomised |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Chronic kidney disease Heart failure RAAS Potassium binder Randomised |
| url | https://doi.org/10.1186/s12882-021-02439-2 |
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