Lokelma for RAAS Maximisation in CKD & Heart Failure.
Status:
Not yet recruiting
Trial end date:
2023-05-01
Target enrollment:
Participant gender:
Summary
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.