Eplerenone Versus Placebo in End-Stage Renal Disease Patients Undergoing Kidney Transplantation: A Double-Blind, Randomized, Placebo-Controlled Trial

The primary objective of this study is to evaluate the impact of **Eplerenone** versus placebo on renal function, specifically assessed by the glomerular filtration rate, at 3 months post-kidney transplantation. This parameter is crucial as it is strongly associated with long-term graft survival, providing insights into the potential benefits of Eplerenone in improving outcomes for patients undergoing kidney transplantation.

Secondary objectives include determining the impact of Eplerenone versus placebo on several clinical outcomes:

• The necessity of dialysis or a glomerular filtration rate of less than 30 ml/min/1.73m² at 3 months post-transplantation.
• The delay to graft recovery.
• Proteinuria at 3 months post-transplantation.
• The occurrence of hyperkalemia greater than 6 mmol/L in the first week post-transplantation.
• The duration of initial hospitalization following transplantation.
• Graft function, graft survival, and patient survival evaluated at 1 year, 3 years, and 10 years post-transplantation.
• The incidence of acute rejection within the first 3 months post-transplantation.

The clinical trial involves participants who are **patients in end-stage renal disease** and candidates for a kidney transplant. The study population includes both male and female subjects, aged 18 years and older. Participants are required to be candidates for a single or dual kidney transplantation from an expanded criteria deceased donor, which includes donors aged 60 years or older, or those aged between 50 and 59 with specific health criteria. All participants must be undergoing chronic hemodialysis and be affiliated with a social security system. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **double-blind**, **placebo-controlled**, randomized study to evaluate the impact of **eplerenone** on renal function following kidney transplantation. The primary objective is to assess the effect of eplerenone versus placebo on renal function, specifically the glomerular filtration rate, at three months post-transplantation. The trial will involve patients with end-stage renal disease who are candidates for kidney transplantation. The study is expected to run from October 2016 to August 2031, with participant involvement lasting approximately three months.

Participants will be randomly assigned to receive either eplerenone or a placebo for four days before and immediately after transplantation. The trial will include several key visits: an initial screening visit to confirm eligibility, baseline assessments, and follow-up visits at specified intervals to monitor renal function and other health parameters. The primary endpoint is the clearance of **iohexol** at three months, while secondary endpoints include the proportion of dialysis dependency, delayed graft function, and the occurrence of hyperkalemia, among others.

Inclusion criteria require participants to be over 18 years of age, provide informed consent, and be candidates for kidney transplantation from an expanded criteria deceased donor. Exclusion criteria are not specified in the provided data. Participants may be withdrawn from the study if they experience adverse events or if they do not adhere to the study protocol. The trial aims to provide valuable insights into the potential benefits of mineralocorticoid receptor blockade in improving renal graft function and long-term survival.

The clinical trial involves the administration of **Eplerenone**, marketed under the name INSPRA 50 mg, in the form of a **film-coated tablet**. Eplerenone is a mineralocorticoid receptor antagonist used in this study to assess its impact on renal function post-kidney transplantation. The pharmaceutical form is a film-coated tablet, and the route of administration is **oral use**. The maximum daily dose is 50 mg, with a total maximum dose of 200 mg over a treatment period of 4 days. The trial aims to evaluate the effect of Eplerenone on graft function, specifically the glomerular filtration rate, at 3 months post-transplantation.

The study also includes a **placebo** group, which receives capsules containing lactose monohydrate with cochineal carmine. This placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators know which treatment is being administered. The placebo is designed to mimic the appearance and administration route of the active treatment, ensuring consistency in the trial's methodology.

Additionally, the trial utilizes **Omnipaque 300 mg d'I/ml**, a solution for injection containing **Iohexol**. This auxiliary treatment is administered intravenously and is used as a contrast agent to facilitate imaging studies that may be required during the trial. The maximum daily and total dose of Iohexol is 3,235,000 micrograms, with a treatment period limited to 1 day. The use of Iohexol is intended to support the assessment of renal function and other relevant clinical parameters during the study.

Efficacy in this clinical trial will be assessed by evaluating the impact of **Eplerenone** versus placebo on renal function, specifically through the measurement of glomerular filtration rate (GFR) at 3 months post-kidney transplantation. This primary endpoint is chosen due to its strong association with long-term graft survival. The primary efficacy parameter, **Iohexol clearance**, will be measured at 3 months to assess renal function. Secondary endpoints include the proportion of dialysis dependency at 3 months, the proportion of patients with delayed graft function at 7 days post-transplantation, 24-hour proteinuria and microalbuminuria at 3 months, occurrence of hyperkalemia greater than 6 mmol/L at 7 days post-transplantation, length of initial hospital stay, and the proportion of patients alive with GFR at 3 months, 1 year, 3 years, and 10 years post-transplantation. Additionally, the proportion of patients with biopsy-proven acute rejection at 3 months post-transplantation will be evaluated. These parameters will be collected and analyzed at specified timepoints to determine the efficacy of the intervention in improving renal function and overall patient outcomes following renal transplantation.