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Potassium Canrenoate in Brain-dead Organ Donors: Randomized Controlled Clinical Trial (CANREO-PMO)

Primary Purpose

Brain-dead Organ Donors

Status
Recruiting
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
IV Potassium Canrenoate
IV Sodium Chloride 0.9 %
Sponsored by
Central Hospital, Nancy, France
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Brain-dead Organ Donors focused on measuring brain-dead organ donors, mineralocorticoid receptor, Kidney

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • CHRU de NANCYRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Potassium canrenoate

Placebo (SODIUM CHLORIDE SOLUTION 0.9%)

Arm Description

Potassium canrenoate 200mg diluted in SODIUM CHLORIDE SOLUTION 0.9%

SODIUM CHLORIDE SOLUTION 0.9%

Outcomes

Primary Outcome Measures

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.
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.
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.
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.

Secondary Outcome Measures

Mortality rate of the kidney recipients
The number of patients dead after kidney transplantation
Serum creatinine (in μmol / L) of kidney recipients
With estimation of the glomerular filtration rate (GFR) according to CKD-EPI (in mL / min / 1.73m2).
Percentage of kidney recipients dependent on dialysis and / or with an estimated GFR <20 mL / min / 1.73m²
Number of patients on dialysis

Full Information

First Posted
January 5, 2021
Last Updated
September 13, 2023
Sponsor
Central Hospital, Nancy, France
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1. Study Identification

Unique Protocol Identification Number
NCT04714710
Brief Title
Potassium Canrenoate in Brain-dead Organ Donors: Randomized Controlled Clinical Trial
Acronym
CANREO-PMO
Official Title
Evaluation of the Hemodynamic Stability of Potassium Canrenoate in Brain-dead Organ Donors: Randomized Controlled Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 26, 2021 (Actual)
Primary Completion Date
February 26, 2024 (Anticipated)
Study Completion Date
February 26, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Central Hospital, Nancy, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain-dead Organ Donors
Keywords
brain-dead organ donors, mineralocorticoid receptor, Kidney

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Single center, double blinded randomized controlled clinical trial
Masking
ParticipantCare ProviderInvestigator
Masking Description
placebo (sodium chloride solution 0.9%) similar to potassium canrenoate diluted in sodium chloride solution 0.9%
Allocation
Randomized
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Potassium canrenoate
Arm Type
Experimental
Arm Description
Potassium canrenoate 200mg diluted in SODIUM CHLORIDE SOLUTION 0.9%
Arm Title
Placebo (SODIUM CHLORIDE SOLUTION 0.9%)
Arm Type
Placebo Comparator
Arm Description
SODIUM CHLORIDE SOLUTION 0.9%
Intervention Type
Drug
Intervention Name(s)
IV Potassium Canrenoate
Other Intervention Name(s)
Drug
Intervention Description
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
Intervention Name(s)
IV Sodium Chloride 0.9 %
Other Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Donor death (cardio circulatory arrest)
Description
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.
Time Frame
from the randomization until the organ removal, up to 24 hours
Title
Inability to perform kidney harvest
Description
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.
Time Frame
Up to 24 hours, in the organ removal during surgery
Title
The average hourly dose of norepinephrine or epinephrine
Description
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.
Time Frame
From the randomization until the departure to the operating room, up to 24 hours
Title
The average hourly volume of crystalloids and / or colloids
Description
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.
Time Frame
from the randomization until the departure to the operating room, up to 24 hours
Secondary Outcome Measure Information:
Title
Mortality rate of the kidney recipients
Description
The number of patients dead after kidney transplantation
Time Frame
3 months, 1 year, 3 years, and 10 years from kidney transplant
Title
Serum creatinine (in μmol / L) of kidney recipients
Description
With estimation of the glomerular filtration rate (GFR) according to CKD-EPI (in mL / min / 1.73m2).
Time Frame
3 months, 1 year, 3 years, and 10 years from kidney transplant
Title
Percentage of kidney recipients dependent on dialysis and / or with an estimated GFR <20 mL / min / 1.73m²
Description
Number of patients on dialysis
Time Frame
3 months after kidney transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Philippe GUERCI, MD, PhD
Phone
(0) 3 83 15 41 66
Ext
+33
Email
P.GUERCI@chru-nancy.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Nicolas GIRERD, MD-PhD
Phone
(0) 3 83 15 73 22
Ext
+33
Email
n.girerd@chru-nancy.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Philippe GUERCI, MD, PhD
Organizational Affiliation
CHRU de NANCY
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Nicolas GIRERD, MD-PhD
Organizational Affiliation
CHRU de NANCY
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Patrick ROSSIGNOL, MD-PhD
Organizational Affiliation
CHRU de NANCY
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Luc FRIMAT, MD-PhD
Organizational Affiliation
CHRU de NANCY
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Hélène GREGOIRE, MD
Organizational Affiliation
CHRU de NANCY
Official's Role
Study Chair
Facility Information:
Facility Name
CHRU de NANCY
City
Nancy
ZIP/Postal Code
54500
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Philippe GUERCI, MD, PhD
Email
P.GUERCI@chru-nancy.fr

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Data are available upon reseanable request to the principal investigator in compliance with french regulations.

Learn more about this trial

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

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