Finerenone for AKI: a Multicenter, Randomized, Placebo-Controlled Feasibility Pilot Trial

Finerenone is a nonsteroidal mineralocorticoid receptor antagonist (MRA) that blocks mineralocorticoid receptor overactivation, a pathway implicated in inflammatory and fibrotic processes in the kidney. It is currently approved for use in chronic kidney disease associated with type 2 diabetes and in heart failure. Its potential role in preventing the transition from AKI to irreversible CKD has not yet been established, and its use in this population is considered experimental.

This is a multicenter, randomized, double-blind, placebo-controlled pilot feasibility trial designed to evaluate the tolerability and safety of finerenone initiated in hospitalized adult patients with moderate to severe AKI (defined by at least a doubling of serum creatinine). Approximately 72 participants will be enrolled across 4-5 sites in Quebec and Ontario.

Eligible participants will be randomized in a 1:1 ratio to receive either finerenone 10 mg or matching placebo, administered orally once daily for up to 45 days. Participants will be followed for 90 days.

The primary objective is to assess the tolerability and safety of finerenone compared to placebo in this population. Secondary and exploratory objectives include evaluating biological markers of kidney injury and fibrosis, with the goal of informing the design of a future, larger efficacy trial.

The study is funded by the Kidney Foundation of Canada and is being conducted under an approval from Health Canada specific to this trial.

Inclusion criteria

• Adult patients (≥18 years old) at the time of giving consent
• Admitted to the hospital at the time of giving consent
• KDIGO Stage ≥2 AKI confirmed by at least two separate creatinine measurements (definition: ≥2.0 times baseline creatinine, no urine output criteria)
• Sustained AKI criteria for ≥48 hours since AKI diagnosis
• No AKI progression before randomization (as per the judgement of the investigator)
• Serum potassium ≤4.8 mmol/L within 48 hours before randomization
• Suspected intrinsic AKI (hemodynamic and obstructive AKI has been ruled out according to the judgment of the investigator)
• Participant should be capable of giving signed informed consent, which includes compliance with the requirements and restrictions of the participating site

Exclusion criteria

• Planned hospital discharge within 48 hours
• Any ongoing use of MRA (spironolactone, eplerenone, finerenone), potassium-sparing diuretics (such as triamterene or amiloride), or potassium binders
• Advanced CKD defined as eGFR ≤30 mL/min/1.73m² or undergoing KRT at baseline
• Ongoing KRT at the time of randomization (Stage 3-dialysed AKI that partially/completely recovered and no longer required KRT at randomization can be included)
• Clinically unstable (based on investigator clinical evaluation, i.e., vasopressors, uncontrolled sepsis)
• Confirmed or suspected glomerular disease (other than diabetes) or acute interstitial nephritis requiring immunosuppressive therapy as the primary cause of AKI
• Previous hypersensitivity to finerenone
• Documented history of adrenal insufficiency or Addison's disease
• Concomitant therapy with strong CYP3A4 inhibitors, if conversion to another medication is not feasible
• Clinician judgment that the intervention is contraindicated due to: A) risk of hyperkalemia; B) risk of KRT initiation within the next 7 days (anuria or rapid increase in serum creatinine); C) impossibility to administer potassium binders
• Enrollment in another clinical trial that could impact potassium, GFR, or kidney function
• For women who are able to become pregnant: positive pregnancy test and/or being breastfeeding at screening
• Any other condition or therapy, in the judgement of the Investigator or the Sponsor, which could make the participant unsuitable for this study, including a condition or therapy which the Investigator anticipates will not allow participation for the full planned study period (i.e., condition limiting life expectancy to less than 3 months)