Clinical trial NCT04714710: Potassium Canrenoate in Brain-dead Organ Donors: Randomized Controlled Clinical Trial
Official title: Evaluation of the Hemodynamic Stability of Potassium Canrenoate in Brain-dead Organ Donors: Randomized Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Brain-dead Organ Donors
Keywords: brain-dead organ donors
mineralocorticoid receptor
Kidney
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
First posted: 2021-01-19
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single center, double blinded randomized controlled clinical trial
Primary purpose: PREVENTION

Brief summary: 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.

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)

Eligibility criteria: 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

Primary outcomes:
measure: Donor death (cardio circulatory arrest)
timeFrame: from the randomization until the organ removal, up to 24 hours
measure: Inability to perform kidney harvest
timeFrame: Up to 24 hours, in the organ removal during surgery
measure: The average hourly dose of norepinephrine or epinephrine
timeFrame: From the randomization until the departure to the operating room, up to 24 hours
measure: The average hourly volume of crystalloids and / or colloids
timeFrame: from the randomization until the departure to the operating room, up to 24 hours
Secondary outcomes:
measure: Mortality rate of the kidney recipients
timeFrame: 3 months, 1 year, 3 years, and 10 years from kidney transplant
measure: Serum creatinine (in μmol / L) of kidney recipients
timeFrame: 3 months, 1 year, 3 years, and 10 years from kidney transplant
measure: Percentage of kidney recipients dependent on dialysis and / or with an estimated GFR <20 mL / min / 1.73m²
timeFrame: 3 months after kidney transplant
Other outcomes:
Locations:
city: Nancy
country: France
facility: CHRU de NANCY
Study officials:
affiliation: CHRU de NANCY
name: Philippe GUERCI, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHRU de NANCY
name: Nicolas GIRERD, MD-PhD
role: STUDY_CHAIR
affiliation: CHRU de NANCY
name: Patrick ROSSIGNOL, MD-PhD
role: STUDY_CHAIR
affiliation: CHRU de NANCY
name: Luc FRIMAT, MD-PhD
role: STUDY_CHAIR
affiliation: CHRU de NANCY
name: Hélène GREGOIRE, MD
role: STUDY_CHAIR
References: