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| ID | Type | Description | Link |
|---|---|---|---|
| 2024-513809-31-00 | EU Trial (CTIS) Number |
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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.
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)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Potassium canrenoate | Experimental | Potassium canrenoate 200mg diluted in SODIUM CHLORIDE SOLUTION 0.9% |
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| Placebo (SODIUM CHLORIDE SOLUTION 0.9%) | Placebo Comparator | SODIUM CHLORIDE SOLUTION 0.9% |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
| 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. |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHRU de NANCY | Nancy | 54500 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37821131 | Derived | 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. |
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Data are available upon reseanable request to the principal investigator in compliance with french regulations.
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 17, 2025 | Jun 30, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D002191 | Canrenoic Acid |
| D004364 | Pharmaceutical Preparations |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
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Single center, double blinded randomized controlled clinical trial
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placebo (sodium chloride solution 0.9%) similar to potassium canrenoate diluted in sodium chloride solution 0.9%
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|
| 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. |
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| from the randomization until the departure to the operating room, up to 24 hours |
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 |
| D011083 |
| Polycyclic Compounds |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |