Potassium Canrenoate in Brain-dead Organ Donors: Randomized Controlled Clinical Trial (CANREO-PMO)

Evaluation of the Hemodynamic Tolerance of Potassium Canrenoate in Brain-dead Organ Donors: Randomized Controlled Clinical Trial

Given the current organ shortage, improving the quality/efficacy of harvested grafts from expanded criteria donors is essential to substantially increase the number of potential donors. Preclinical studies have shown that blocking the vascular mineralocorticoid receptor (MR) mitigates ischemia-reperfusion injury (I/R) and prevents renal dysfunction following acute kidney injury. Potassium canrenoate is an intravenous MR antagonist. Blocking the MR upstream from aortic cross clamping is likely the most effective strategy to limit I/R injury.

Yet, brain-dead donors are prone to severe hemodynamic instability and polyuria. Consequently, this study seeks to assess the hemodynamic tolerance of the use of potassium canrenoate in this context, as a first step to a large-scale clinical trial testing the impact of this therapeutic intervention on the survival of kidney grafts.

Study Overview

• Status: Active, not recruiting
• Conditions: Brain-dead Organ Donors
• Intervention / Treatment: Drug: IV Potassium Canrenoate; Drug: IV Sodium Chloride 0.9 %

Detailed Description

In this single-center, double-blind, placebo-controlled clinical trial, we seek to evaluate the effect of the administration of 200 mg of IV potassium canrenoate vs placebo in brain-dead donors aged 18 years or more - within 10 hours after the diagnosis of brain death is made and before the departure to operating room.

The primary objective is to assess the impact of potassium canrenoate administration vs. placebo on the hemodynamics of brain-dead subjects who are candidates for kidney or multiple organ harvesting (including renal).

The vital status and renal function of kidney recipients will be followed at 3 months, 1 year, 3 years and 10 years from transplant (main secondary objectives)

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Nancy, France, 54500
    • CHRU de Nancy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men, women aged 18 years or older,
• Encephalic death diagnosed either by 2 flat and areactive 30-minute electroencephalograms performed 4 hours apart or by a cerebral angioTDM objectifying a total cessation of intracranial circulation,
• And from whom a removal of one or both kidneys is envisaged (within 6 hours or more), according to the procedures currently in force at the Agence de la Biomédecine,
• Dosage of vasopressor agent amines that have not varied by more than 1 mg/h in the hour preceding inclusion and dose of vasopressor less than 7 mg / h at inclusion,
• euvolemic donor patient at inclusion,
• Benefiting from a Social Security affiliation scheme.
• Signature of consent by a family member or the support person.

Exclusion Criteria:

• Patient having received potassium canrenoate in the 48 hours preceding inclusion in the study,
• Patient on long-term mineralocorticoid receptor antagonist (eplerenone or spironolactone),
• Having a serum potassium concentration> 5.5 mmol / L on inclusion,
• Contraindications to multi-organ removal (infectious, neoplastic causes, etc.),
• Refusal of organ removal expressed by the patient (national register of refusals or reported by the family),
• Probable inability to remove the kidneys: history of urine-renal disease, pre-existing chronic renal failure, morphological abnormalities of the kidneys, renal trauma,
• Patients enrolled in another interventional drug trial,
• Person with a contraindication to potassium canrenoate and/or trometamol,
• Severe renal failure,
• Severe atrioventricular conduction disorders,
• Terminal stage of hepatocellular failure,
• Pregnant, parturient or lactating woman,
• Persons deprived of their liberty by a judicial or administrative decision,
• Minors (non emancipated)
• Adults subject to legal protection measures (guardianship, curatorship, safeguard of justice).
• Person undergoing psychiatric care under articles L3212-1 and L3213-1 of the french Public Health Code

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Potassium canrenoate; Potassium canrenoate 200mg diluted in SODIUM CHLORIDE SOLUTION 0.9%	Drug: IV Potassium Canrenoate; Administration of 200 mg of IV potassium canrenoate (diluted in sodium chloride 0.9%) in brain-dead donors within 10 hours after the diagnosis of brain death and before the departure to the operating room. Second administration of potassium canrenoate 6 hours after first administration if the patient is not YET admitted IN the operating room; Other Names: Drug
Placebo Comparator: Placebo (SODIUM CHLORIDE SOLUTION 0.9%); SODIUM CHLORIDE SOLUTION 0.9%	Drug: IV Sodium Chloride 0.9 %; Administration of IV sodium chloride 0.9% (placebo) in brain-dead donors within 10 hours after the diagnosis of brain death is made and before the departure to the operating room. Second administration of IV sodium chloride 0.9% (placebo) 6 hours after first administration if the patient is not YET admitted IN the operating room.; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Donor death (cardio circulatory arrest)	The primary endpoint will be a hierarchical composite of events, as described by Felker in 2010 (Circ HF - PMID 20841546) including in descending order: A. death (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, D. the average hourly volume of crystalloids and / or colloids used between randomization and departure to the operating room.	from the randomization until the organ removal, up to 24 hours
Inability to perform kidney harvest	The primary endpoint will be a hierarchical composite of events, as described by Felker in 2010 (Circ HF - PMID 20841546) including in descending order: A. death (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, D. the average hourly volume of crystalloids and / or colloids used between randomization and departure to the operating room.	Up to 24 hours, in the organ removal during surgery
The average hourly dose of norepinephrine or epinephrine	The primary endpoint will be a hierarchical composite of events, as described by Felker in 2010 (Circ HF - PMID 20841546) including in descending order: A. death (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, D. the average hourly volume of crystalloids and / or colloids used between randomization and departure to the operating room.	From the randomization until the departure to the operating room, up to 24 hours
The average hourly volume of crystalloids and / or colloids	The primary endpoint will be a hierarchical composite of events, as described by Felker in 2010 (Circ HF - PMID 20841546) including in descending order: A. death (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, D. the average hourly volume of crystalloids and / or colloids used between randomization and departure to the operating room.	from the randomization until the departure to the operating room, up to 24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality rate of the kidney recipients	The number of patients dead after kidney transplantation	3 months, 1 year, 3 years, and 10 years from kidney transplant
Serum creatinine (in μmol / L) of kidney recipients	With estimation of the glomerular filtration rate (GFR) according to CKD-EPI (in mL / min / 1.73m2).	3 months, 1 year, 3 years, and 10 years from kidney transplant
Percentage of kidney recipients dependent on dialysis and / or with an estimated GFR <20 mL / min / 1.73m²	Number of patients on dialysis	3 months after kidney transplant

Collaborators and Investigators

• Sponsor: Pr. Nicolas GIRERD
• Investigators: Principal Investigator: Philippe GUERCI, MD, PhD, CHRU de Nancy; Study Chair: Luc FRIMAT, MD-PhD, CHRU de Nancy; Study Chair: Hélène GREGOIRE, MD, CHRU de Nancy; Study Chair: Nicolas GIRERD, MD-PhD, CHRU de Nancy; Study Chair: Patrick ROSSIGNOL, MD-PhD, CHRU de Nancy

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2021
• Primary Completion (Actual): December 6, 2023
• Study Completion (Estimated): December 6, 2033

Study Registration Dates

• First Submitted: January 5, 2021
• First Submitted That Met QC Criteria: January 15, 2021
• First Posted (Actual): January 19, 2021

Study Record Updates

• Last Update Posted (Actual): July 3, 2025
• Last Update Submitted That Met QC Criteria: June 30, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Kidney; mineralocorticoid receptor; brain-dead organ donors
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neurobehavioral Manifestations; Death; Consciousness Disorders; Unconsciousness; Coma; Brain Death; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Diuretics; Natriuretic Agents; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Canrenoic Acid
• Other Study ID Numbers: 2020-003285-40; 2024-513809-31-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data are available upon reseanable request to the principal investigator in compliance with french regulations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No