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Lokelma for RAAS Maximisation in CKD & Heart Failure.

NCT05004363 · Status: COMPLETED · Phase: PHASE3 · Type: INTERVENTIONAL · Enrollment: 112

Last updated 2026-04-27

No results posted yet for this study

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.

Conditions

  • Chronic Kidney Diseases
  • Heart Failure With Reduced Ejection Fraction
  • Hyperkalemia
  • ACE Inhibitor Induced Hyperkalaemia
  • Mineralocorticoid Resistant Hyperkalemia

Interventions

DRUG

Lokelma Oral Product

Potassium binder

Sponsors & Collaborators

  • St George's, University of London

    lead OTHER

Principal Investigators

  • Debasish Banerjee, MD FRCP · St Georges's, University of London

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Model
PARALLEL

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2022-01-19
Primary Completion
2024-07-01
Completion
2024-07-01

Countries

  • United Kingdom

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05004363 on ClinicalTrials.gov