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

NCT04714710 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: 2020-003285-402024-513809-31-00
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Brain-dead Organ Donors

Keywords

brain-dead organ donors; mineralocorticoid receptor; Kidney

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (3)

• Mortality rate of the kidney recipients

  3 months, 1 year, 3 years, and 10 years from kidney transplant

• Serum creatinine (in μmol / L) of kidney recipients

  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

  3 months after kidney transplant

Study Arms (2)

Potassium canrenoate

EXPERIMENTAL

Potassium canrenoate 200mg diluted in SODIUM CHLORIDE SOLUTION 0.9%

Drug: IV Potassium Canrenoate

Placebo (SODIUM CHLORIDE SOLUTION 0.9%)

PLACEBO COMPARATOR

SODIUM CHLORIDE SOLUTION 0.9%

Drug: IV Sodium Chloride 0.9 %

Interventions

IV Potassium Canrenoate 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

Also known as: Drug

Potassium canrenoate

IV Sodium Chloride 0.9 % 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.

Also known as: Placebo

Placebo (SODIUM CHLORIDE SOLUTION 0.9%)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,
• Benefiting from a Social Security affiliation scheme.
• Signature of consent by a family member or the support person.

You may not qualify if:

• Patient on long-term mineralocorticoid receptor antagonist (eplerenone or spironolactone),
• 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

Sponsors & Collaborators

• Pr. Nicolas GIRERD: lead

Study Sites (1)

CHRU de NANCY

Nancy, 54500, France

Location

Related Publications (1)

• 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.

  PMID: 37821131 DERIVED

MeSH Terms

Interventions

Canrenoic Acid; Pharmaceutical Preparations; Sodium Chloride

Intervention Hierarchy (Ancestors)

Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Philippe GUERCI, MD, PhD

  CHRU de NANCY

  PRINCIPAL INVESTIGATOR

• Nicolas GIRERD, MD-PhD

  CHRU de NANCY

  STUDY CHAIR

• Patrick ROSSIGNOL, MD-PhD

  CHRU de NANCY

  STUDY CHAIR

• Luc FRIMAT, MD-PhD

  CHRU de NANCY

  STUDY CHAIR

• Hélène GREGOIRE, MD

  CHRU de NANCY

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: placebo (sodium chloride solution 0.9%) similar to potassium canrenoate diluted in sodium chloride solution 0.9%
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Study Chair

Model Details: Single center, double blinded randomized controlled clinical trial

Study Record Dates

• First Submitted: January 5, 2021
• First Posted: January 19, 2021
• Study Start: August 26, 2021
• Primary Completion: December 6, 2023
• Study Completion (Estimated): December 6, 2033
• Last Updated: July 3, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

FR (1)