Assessment of Hemodynamic Tolerance of Potassium Canrenoate in Brain-Dead Organ Donors: A Randomized Controlled Trial

The primary objective of this study is to evaluate the impact of **potassium canrenoate** administration versus placebo on the hemodynamics of brain-dead subjects who are candidates for kidney or multiple organ harvesting. This is clinically relevant as optimizing hemodynamic stability in brain-dead organ donors can potentially improve the quality and viability of transplanted organs, thereby enhancing transplant outcomes.

Secondary objectives include:

• Assessing the impact of potassium canrenoate administration versus placebo on the function of the graft at 3 months post-transplantation in kidney recipients from these donors.
• Evaluating the presence of dialysis or a glomerular filtration rate (GFR) estimated according to CKD-EPI <20 mL/min/1.73m² at 3 months in kidney recipients from these donors.
• Assessing the survival of kidney recipients from these donors evaluated at 3 months.
• Evaluating renal function, graft survival, and survival of kidney recipients from these donors at 1 year, 3 years, and 10 years post-transplantation.

The clinical trial involves a study population comprising **brain-dead organ donors** who are candidates for kidney or multiple organ harvesting. The participants include both **male** and **female** subjects aged 18 years or older. The trial focuses on individuals who have been diagnosed with encephalic death, confirmed by specific diagnostic criteria such as electroencephalograms or cerebral CT angiography. The trial population is selected based on their potential for organ donation, with a particular emphasis on those from whom kidney harvesting is envisaged. Participants are required to be euvolemic at inclusion and have a stable dose of vasopressor agents prior to inclusion. The trial includes individuals affiliated with a Social Security scheme and requires signed consent from a designated support person or family member. The sponsor has not provided information regarding the total number of participants in this study.

The clinical trial is designed to evaluate the **hemodynamic tolerance** of **potassium canrenoate** in brain-dead organ donors. This is a **randomized, controlled, double-blind** trial, conducted in Phase 4, with the primary objective of assessing the impact of potassium canrenoate administration versus placebo on the hemodynamics of brain-dead subjects who are candidates for kidney or multiple organ harvesting. The trial is expected to run from August 26, 2021, to June 5, 2033, with participant involvement lasting up to one day, as the maximum treatment period is one day.

Participants will undergo a sequence of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (18 years or older), confirmed encephalic death, and the potential for kidney harvesting. The inclusion visit will also ensure that the dose of vasopressor agents has not varied significantly prior to inclusion and that the patient is euvolemic. Following randomization, participants will receive either the test product, **SOLUDACTONE 200 mg** (potassium canrenoate), or the placebo, **CHLORURE DE SODIUM 0.9%** (sodium chloride), both administered intravenously. The primary endpoint is a hierarchical composite of events, including cardio circulatory arrest before organ removal and the inability to perform the renal swab.

Secondary endpoints will be evaluated by consulting data from the CRISTAL database, focusing on the vital status and renal function of kidney recipients at various intervals post-transplant. The end-of-study visit will occur upon completion of the treatment period, with data collection continuing for up to 10 years post-transplant for secondary objectives. Participants may be terminated early from the study if they experience significant adverse events or if the criteria for inclusion are no longer met. The trial aims to provide valuable insights into the potential benefits of potassium canrenoate in improving outcomes for organ donors and recipients.

The clinical trial involves the administration of **SOLUDACTONE 200 mg**, a lyophilisate and solution for parenteral use, which is a **solution for injection**. The active substances in this experimental medication are **potassium canrenoate** and trometamol, both of which are of chemical origin. The medication is administered intravenously. The maximum daily dose is 400 mg, with a total maximum dose of 400 mg over a treatment period of one day. The pharmaceutical form is specifically designed for injection, ensuring precise delivery of the active substances. The trial aims to evaluate the hemodynamic tolerance of potassium canrenoate in brain-dead organ donors.

In addition to the experimental treatment, the study utilizes **CHLORURE DE SODIUM 0.9% BAXTER**, a solution for infusion, as a placebo. This non-experimental treatment contains **sodium chloride** as its active substance, also of chemical origin. The solution is administered intravenously, with a maximum daily and total dose of 1.8 grams over a one-day treatment period. The use of this placebo allows for a controlled comparison to assess the impact of the experimental medication on the hemodynamics of the participants. Compliance with the dosing schedule is monitored to ensure the integrity of the trial results.

The efficacy of the clinical trial titled "Evaluation of the hemodynamic tolerance of **potassium canrenoate** in brain-dead organ donors: randomized controlled clinical trial 'CANREO-PMO'" will be assessed using a hierarchical composite of events as the primary endpoint. This composite includes, in descending order: A. Cardio circulatory arrest before organ removal, B. the inability to perform the renal swab, C. the average hourly dose of noradrenaline/adrenaline between randomization and departure to the operating room, and D. the average hourly volume of crystalloids and/or colloids used between randomization and departure to the operating room.

Secondary endpoints will be evaluated by consulting data from the CRISTAL database. These include: 1. The vital status and serum creatinine levels with estimation of the glomerular filtration rate (GFR) according to CKD-EPI, 3 months after kidney transplant, 2. The percentage of patients dependent on dialysis and/or with an estimated GFR <20 mL/min/1.73m² at 3 months, 3. The vital status of kidney recipients from these donors at 3 months, and 4. The vital status of kidney recipients from these donors and serum creatinine levels with estimation of the GFR according to CKD-EPI, at 1 year, 3 years, and 10 years from transplant.