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

2020-003285-40

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.

2021-08-26

2024-02-26

2025-02-26

Recruiting

Early phase I

36

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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Single center, double blinded randomized controlled clinical trial', 'primaryPurpose': 'PREVENTION', 'maskingInfo': {'masking': 'TRIPLE', 'maskingDescription': 'placebo (sodium chloride solution 0.9%) similar to potassium canrenoate diluted in sodium chloride solution 0.9%', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}}, 'enrollmentInfo': {'count': 36, 'type': 'ESTIMATED'}}

2023-09-15