Which investigational agents or combinations of agents are effective in reducing the rate of eGFR decline, compared to placebo, in patients with chronic kidney disease who are receiving standard of care therapy?

MRA Domain-Specific Appendix: Is finerenone effective in reducing the rate of eGFR decline, compared to placebo, in patients with chronic kidney disease who are receiving standard of care therapy?

Study sites:

National Hospital of Sri Lanka, National Nephrology Specialized Hospital, Colombo North Teaching Hospital, National Hospital Kandy, Teaching Hospital Kurunegala, Teaching Hospital Peradeniya, Sri Jayewardenepura General Hospital

Randomisation: Eligible participants will be randomised equally (1:1) between finerenone and matched placebo. Randomisation will be stratified within each site for the Mineralocorticoid Receptor Antagonist Domain-Specific Appendix (MRA DSA). A computer-generated randomisation schedule using randomly-permuted blocks will be used to maintain balance within each stratum.

Intervention: Participants will be randomised to either finerenone or matched placebo. The dosage of the study medication is informed by the participant’s kidney function and serum potassium levels. The first dose of the allocated study medication will be administered as soon as possible (within 7 days) after randomisation. The placebo tablet contains Magnesium stearate and lactose monohydrate.

Participants must continue to receive standard of care therapy as per local guideline recommendations during their participation.

Blinding plan:

CAPTIVATE is primarily a double-blinded trial, where participants, investigators, site personnel, and trial statisticians remain blinded to treatment allocation until database lock for their respective comparisons. However, blinding may not be feasible for certain behavioral or device-based interventions; these will be specified in the Domain-Specific Appendices (DSAs).

Unblinded access is restricted to: • Data managers handling randomisation and drug management • Unblinded statisticians supporting adaptive randomisation and DSMB reporting • Pharmacovigilance staff for regulatory reporting

Emergency unblinding is allowed only when essential for participant safety and must be limited to those directly involved in clinical care.

Participants and treating physicians may be unblinded to the intervention after completion of the interventional comparison and acceptance of the primary manuscript for publication.

Core protocol:

Potential participants must satisfy all of the following: 1. Age: ?18 years 2. Gender:both males and females 3. Known chronic kidney disease from any cause (eGFR ?25 mL/min/1.73m2) 4. Currently receiving standard of care treatment according to treating physician 5. Eligible for randomisation in at least one recruiting domain-specific appendix 6. Participant and treating physician are willing and able to perform trial procedures 7. Provision of written informed consent or eConsent prior to performing any protocol related procedures

MRA Domain-Specific Appendix:

Potential participants must satisfy all of the inclusion criteria in the Core Protocol, and also satisfy the following: 1. Urine albumin-creatinine ratio (uACR) >200 mg/g (22.6 mg/mmol) or urine protein-creatinine ratio (uPCR) >300 mg/g (33.9 mg/mmol) from the most recent result in the previous 3 months. 2. On a stable standard of care treatment for chronic kidney disease, including a SGLT2i unless there is a documented reason not to be using a SGLT2i*, for 4 weeks before screening according to treating physician. 3. Treating physician believes finerenone is clinically appropriate for the participant. 4. Participant and treating physician are willing and able to perform MRA DSA procedures. 5. Provision of written informed consent or eConsent prior to performing any MRA DSA related procedures.

*Potential reasons for not using a SGLT2i could include intolerance (including allergy or absolute contraindication), cost or inaccessibility (including unavailability), participant refusal or physician decision.

Core protocol:

Potential participants must have none of the following: 1. Currently receiving maintenance dialysis 2. Planned to commence kidney replacement therapy or kidney transplant surgery in next 6 months 3. Life expectancy less than 6 months

MRA Domain-Specific Appendix:

Potential participants must have none of the exclusion criteria in the Core Protocol, and must have none of the following:

1. Recipient of kidney transplant
2. Hyperkalaemia (serum potassium ?5.0 mmol/L) at time of screening
3. Current treatment with Mineralocorticoid Receptor Antagonist (MRA), where the treating physician or patient is not willing to discontinue this medication. If willing to discontinue the MRA, the potential participant must be re-screened after they have been on stable standard of care treatment for 4 weeks without the MRA.
4. Known allergy, intolerance or contraindication to MRAs
5. Current treatment with strong CYP3A4 inhibitors
6. Systolic Blood Pressure <110 mmHg or diastolic BP<55 mmHg without antihypertensive therapy at time of screening
7. Severe hepatic impairment
8. Adrenal insufficiency
9. Currently pregnant or breast feeding, or intending to become pregnant