Lokelma for RAAS Maximisation in CKD & Heart Failure.

NCT05004363 | Completed Phase 3 DMC

• 2 other identifiers: 2020.00712020-002946-18
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief 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; Hyperkalemia; ACE Inhibitor Induced Hyperkalaemia; Mineralocorticoid Resistant Hyperkalemia; Heart Failure With Reduced Ejection Fraction

Keywords

Acute Kidney Injury; Sodium Zirconium Cyclosilicate

Outcome Measures

Primary Outcomes (1)

• Number of participants who achieve the maximum dose

  Ramipril 5 mg OD + Spironolactone 25 mg OD for patients on a baseline RAASi dose that is less than Ramipril 5 mg OD + Spironolactone 25 mg OD or equivalent Ramipril 10 mg OD + Spironolactone 50 mg OD for patients on a baseline RAASi dose that is more or equal than Ramipril 5 mg OD + Spironolactone 25 mg OD or equivalent

  16 weeks

Secondary Outcomes (1)

• Number of participants achieving other outcomes

  16 weeks

Study Arms (2)

Lokelma

ACTIVE COMPARATOR

Lokelma therapy

Drug: Lokelma Oral Product

Control

PLACEBO COMPARATOR

Placebo

Drug: Lokelma Oral Product

Interventions

Lokelma Oral Product DRUG

Potassium binder

Also known as: placebo

Control; Lokelma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 years
• Heart failure, clinical or echo confirmed (HFrEF); patients with AF will be included provided the EF can be determined
• NYHA class II to IV
• Serum potassium 5.0-5.5 mmol/L
• Adequate blood pressure (\>90 mm Hg systolic and without postural hypotension; drop of Systolic Blood Pressure \>20 or feeling dizzy with change in posture; exclude patients with symptomatic hypotension due to high doses of ACEi/ARB or MRA unless the clinical condition has improved)
• CKD with stable eGFR \<60 ml/min/1.73m2
• None or submaximal dose of ACEi/ARB and/or MRA or both

You may not qualify if:

• Pregnancy
• Active malignancy or infection
• BMI\>35 kg/m2
• Poorly controlled sugar HBA1C\> 70 mmol/mmol
• Recent ACS
• Potassium therapy
• Prolonged QT\>550msec, congenital QT syndrome and history of prolong QT requiring drug discontinuation

Sponsors & Collaborators

• St George's, University of London: lead

Study Sites (1)

St Georges, University of London

London, United Kingdom

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Hyperkalemia; Pseudohypoaldosteronism; Acute Kidney Injury

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Renal Tubular Transport, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Debasish Banerjee, MD FRCP

  St Georges's, University of London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: RCT

Study Record Dates

• First Submitted: June 8, 2020
• First Posted: August 13, 2021
• Study Start: January 19, 2022
• Primary Completion: July 1, 2024
• Study Completion: July 1, 2024
• Last Updated: April 27, 2026

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)