P0200KEEP ON (KEEPING RAAS INHIBITION TREATMENT WITH OPTIMAL POTASSIUM CONTROL). DESIGN OF A CLINICAL TRIAL OF USING SODIUM ZIRCONIUM CYCLOSILICATE FOR KEEPING RAAS INHIBITION AND/OR MRAS IN PATIENTS WITH CKD AND CONGESTIVE HEART FAILURE HISTORY. (6th June 2020) - Puchades Montesa, Maria Jesãºs
Abstract: Background and Aims: Hyperkalemia (HK) is a potentially life-threatening condition, in patients with chronic kidney disease (CKD) and congestive heart failure (CHF). The majority of patients affected with CKD or CHF, must be treated with inhibitors of renin angiotensin aldosterone system (RAASi) and mineralocorticoid receptor antagonists (MRAs). However, the treatments previously mentioned, increase the risk of HK episodes, which is the main cause of RAASi and MRAs downtitration or discontinuation, representing an undesirable clinical scenario, given that the patients are at high risk of be deprived of their nephroprotective effect and cardio-renal benefits The aim of the study is: to analyze if, in patients with HK, CKD and CHF treated with RAASi and/or MRA, serum potassium (sK) reduction by Sodium zirconium cyclosilicate (SZC) treatment is non-inferior to RAASi and/or MRAs discontinuation or downtitration. Method: Design: Randomized, Multicentric, open label, parallel-group, non-inferiority 12 weeks trial, comparing SZC vs discontinuation or downtitration of RAASi and /or MRA as standard of care. Key Inclusion Criteria: Patients with hyperkaliemia (defined as sK: 5.5-6.5 mEq/L) and non dyalisis CKD (Stages 2-5) and previous history of CHF (cardiorenal syndrome), receiving RAASi and / or MRAs. Primary efficacy end-point: To determine the proportion of patients achieving sK<5 with SZC treatmentversus discontinuation or downtitration of RAASi and/or MRAs at day 90. As Main secondary objectives: To evaluate Non-inferiority of SZC versus RAASi/MRAs discontinuation or down-titration with respect to achieve sK< 5 m Eq/L or effectively reduces sK > 20 % over the baseline at 7, 30, 60 and 90 days. To evaluate the implication of SZS treatment on the reduction of the necessity of additional treatment for hyperkaliemia compared to RAASi and/or MRAs discontinuation. To measure the impact of the treatment of SZC on the quality life of HK patients measured by KDQoL questionnaire (Self-Assessment Questionnaire). To measure the changes in albuminuria at 90 days from baseline. Sample size calculation: Proportion of patients reaching sK of <5 at 90 days with SZC is estimated to be 0.9 while discontinuation of RAASi and/or MRAs 0.80. Considering a non-inferiority margin of 0.1 and type I error rate of 5%, a total of 78 patients (39 per group) are required to achieve a power of 80%.Study conduct: the patients who meet inclusion criteria will be randomized to SZC group or RAAS-I and/or MRAs downtitration or discontinuation. Visits on days: 2, 3, 7, 30, 60 and 90. SZC group: patients will continue treatment with RAAS-I and/or MRAs and they will receive 10 g (sachets) thrice a day. According to sK levels, SZC dosage will be adjusted in each visit (Maintained 10 g thrice a day or reduced up to 5 g once a day or discontinuation if sK<3 mEq/L). If confirmed sK ≥ 6.5 mE/L despite the maximum SZC dose, patient will leave the study and will be counted as treatment failure. Treatment for acute hyperkaliemia will be started following common clinical practice and local protocols. Control group: RAAS-I and/or MRAs will be discontinued or downtitrated at investigator's judgment. If sK ≥ 6.5 mE/L, treatment for acute hyperkaliemia will be started. Patient will leave the study and will be counted as treatment failure. Results: The study will demonstrate results on serum electrolytes, renal function, albuminuria, KDQoL questionnaire and changes in relative overhydration (multifrequency bioimpedance -BCM Fresenius-) Conclusion: The KEEP ON study will define the ability of SZC to facilitate the use of RAAS-I and / or MRA in patients with HK and cardiorenal syndrome allowing the maintenance of the medications recommended by international guidelines for the treatment of CHF at different degrees of CKD while maintaining the potential cardio-renal and nephroprotective benefit.