Potassium Canrenoate in Brain-dead Organ Donors: Randomized Controlled Clinical Trial

NCT ID: NCT04714710

Last Updated: 2025-07-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-26
• Study Completion Date: 2033-12-06

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)

Conditions

Brain-dead Organ Donors

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Potassium canrenoate

Potassium canrenoate 200mg diluted in SODIUM CHLORIDE SOLUTION 0.9%

Group Type: EXPERIMENTAL

IV Potassium Canrenoate

Intervention Type: DRUG

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

Placebo (SODIUM CHLORIDE SOLUTION 0.9%)

SODIUM CHLORIDE SOLUTION 0.9%

Group Type: PLACEBO_COMPARATOR

IV Sodium Chloride 0.9 %

Intervention Type: DRUG

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.

Interventions

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

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Drug; Placebo

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pr. Nicolas GIRERD

OTHER

Sponsor Role: lead

Responsible Party

Pr. Nicolas GIRERD

Study Chair

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Philippe GUERCI, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

CHRU de NANCY

Nicolas GIRERD, MD-PhD

Role: STUDY_CHAIR

CHRU de NANCY

Patrick ROSSIGNOL, MD-PhD

Role: STUDY_CHAIR

CHRU de NANCY

Luc FRIMAT, MD-PhD

Role: STUDY_CHAIR

CHRU de NANCY

Hélène GREGOIRE, MD

Role: STUDY_CHAIR

CHRU de NANCY

Locations

CHRU de NANCY

Nancy, , France

Countries

France

References

Belarif L, Girerd S, Jaisser F, Lepage X, Merckle L, Duarte K, Girerd N, Guerci P. Potassium canrenoate in brain-dead organ donors: a randomised controlled clinical trial protocol (CANREO-PMO). BMJ Open. 2023 Oct 11;13(10):e073831. doi: 10.1136/bmjopen-2023-073831.

Reference Type: DERIVED

PMID: 37821131 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2024-513809-31-00

Identifier Type: CTIS

Identifier Source: secondary_id

2020-003285-40

Identifier Type: -

Identifier Source: org_study_id