Acute Kidney Injury, Renal Insufficiency,Chronic, Kidney Diseases
Conditions
Keywords
Finerenone, Acute kidney injury, AKI to CKD transition, Chronic kidney disease, Renal fibrosis, Mineralocorticoid receptor antagonist, Hyperkalemia, Pilot study, Feasibility trial, Nephroprotection
Brief summary
This study is testing whether finerenone, when compared to placebo, is a tolerable and safe intervention when administered in patients with acute kidney injury (AKI). This study will explore whether finerenone can mitigate the risk of transitioning to chronic kidney disease following a moderate to severe AKI. Participants will be randomly assigned to receive either finerenone or a placebo, once daily for up to 45 days, in addition to their standard care. The study will monitor for side effects such as serum potassium levels and blood pressure, and will assess whether the drug helps prevent AKI from progressing to chronic kidney disease. This is a pilot feasibility study involving approximately 72 participants across 4-5 sites in Quebec and Ontario.
Detailed description
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.
Interventions
Finerenone 10mg, oral capsule, administered once daily for up to 45 days
DRUGPlacebo
Matching placebo capsule, identical in appearance to finerenone 10mg, administered orally once daily for up to 45 days
Sponsors
Jean-Maxime Côté
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This is a double-blind study. Neither participants nor their study doctors will know treatment group assignment. Finerenone and placebo will be prepared as identical-appearing capsules, compounded and packaged to be indistinguishable in appearance. Two designated blinded / unblinded CRAs will manage drug allocation and monitoring : unblinding will occur in emergency situations where knowledge of treatment assignment is required for the participant's medical care.
Intervention model description
Participants will be randomized in a 1:1 ratio to receive either finerenone 10mg or matching placebo, administered orally once daily for up to 45 days, in parallel treatment arms, in addition to standard of care.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recruitment success | 2 years from first participant recruited | Enrollment of target population (72 participants) achieved within 2 years from first recruitment, accross at least 3 participating sites |
| Adherence to study drug | Day 1 to Day 45 | Proportion of prescribed doses taken during the 45-day interventional period |
| Follow-up success (retention rate) | Through Day 90 | Proportion of surviving participants retained for the end-of-study visit (Day 90) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of hyperkalemia | Day 1 to Day 45 | Proportion of participants with serum/plasma potassium \>5.5 mmol/L (moderate: 5.5-6.0 mmol/L; severe: \>6.0 mmol/L), measured via local laboratories at any point during the interventional period |
| Incidence of hyponatremia | Day 1 to Day 45 | Proportion of participants with serum/plasma sodium \<130 mmol/L, measured via local laboratories at any point during the interventional period |
| Incidence of GFR worsening | Day 1 to Day 45 | Proportion of participants with ≥50% reduction in eGFR from randomization, calculated using local laboratory creatinine values (CKD-EPI 2021 equation) |
| Change in FiPAKI biomarkers panel | Baseline through Day 90 | Change over time in plasma and urine biomarkers of kidney damage and fibrosis (creatinine, cystatin C, albumin, protein, YKL-40, DKK3, CCL14, TNFR1, Gal3, UMOD, NGAL) |
| Change in eGFR | Baseline to Day 90 | Change from baseline eGFR (calculated using CKD-EPI 2021 equation, race-omitted) at randomization, follow-up visits, and end-of-study |
Countries
Canada
Contacts
CONTACTJean-Maxime Côté, MD, MSc., FRCPC
CONTACTPARC PADOC
PRINCIPAL_INVESTIGATORJean-Maxime Côté, MD, MSc., FRCPC
Centre hospitalier de l'Université de Montréal (CHUM)
Outcome results
None listed