Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruiting
Participants planned
36
Countries
1
Sites
1
Brain-dead Organ Donors
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).
Key facts
- Sponsor
- CHRU De Nancy
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14], Phenomena and Processes [G] - Circulatory and Respiratory Physiological Phenomena [G09]
- Trial duration
- 27 Aug 2024 → ongoing
- Decision date (initial)
- 2024-08-27
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- DGOS - GIRCI EST
External identifiers
- EU CT number
- 2024-513809-31-00
- EudraCT number
- 2020-003285-40
- ClinicalTrials.gov
- NCT04714710
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety
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).
Secondary objectives 4
- Assess the impact of potassium canrenoate administration vs. placebo in brain-dead donor on the function of the graft at 3 months after transplantation in kidney recipients from these donors,
- Assess the impact of potassium canrenoate administration vs. placebo in brain-dead donor on the presence of dialysis or a glomerular filtration rate (GFR) estimated according to CKD-EPI <20mL / min / 1.73m2 at 3 months in kidney recipients from these donors,
- Assess the impact of potassium canrenoate administration vs. placebo in brain-dead donor on the survival of kidney recipients from these donors evaluated at 3 months,
- Assess the impact of potassium canrenoate administration vs. placebo in brain-dead donor on renal function, graft survival, and survival of kidney recipients from these donors evaluated at 1 year, 3 years and 10 years after transplantation.
Conditions and MedDRA coding
Brain-dead Organ Donors
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.0 | PT | 10058985 | Organ donor | 100000004869 |
Study design 2 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Randomized period Patient randomized and followed up to 16h.
|
Randomised Controlled | Double | [{"id":73008,"code":1,"name":"Subject"},{"id":73010,"code":4,"name":"Analyst"},{"id":73009,"code":2,"name":"Investigator"}] | Soludactone group: 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 Control group : placebo: 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. |
| 2 | Long Term folllowed up (up to 10 years) of Graft recipients from donors randomised Long-term follow-up of organ recipients and their grafts from study donors is scheduled for up to 10 years (at 1; 3; 10 years) after the transplant.
|
Not Applicable | None |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 7
- 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 CT angiography showing a non-opacification of the cortical middle cerebral arteries and internal cerebral veins
- And from whom an harvesting 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;
- Dose of vasopressor agent that have not varied by more than 1 mg/h in the hour preceding inclusion and dose of vasopressor pressure less than 7 mg / h at inclusion;
- Euvolemic patient at inclusion;
- Affiliated to Social Security scheme;
- Signed written consent by the support person provided for in article L. 1111-6, or failing this by a family member.
Exclusion criteria 12
- 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 included in another interventional drug clinical trial;
- Known potassium canrenoate and / or trometamol hypersensitivity;
- Severe renal failure;
- Severe atrioventricular conduction disorders
- Terminal stage of hepatocellular insufficiency;
- Persons referred to in articles L. 1121-5, L.1121-6, L. 1121-7 and L1121-8 of France's public health code: -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 Public Health Code.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Hierarchical composite of events including in descending order:A. Cardio circulatory arrest before organ removal, B. the inability to perform the renal swab (since the anticipated effectiveness of the canrenoate would mainly relate to this organ), C. the average hourly dose of noradrenaline / adrenaline between randomisation 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 endpoints 4
- Secondary objectifs will be evaluated by consulting data from the CRISTAL database : Objective 1 : the vital status and serum creatinine (in μmol / L) with estimation of the glomerular filtration rate (GFR) according to CKD-EPI (in mL / min / 1.73m2), 3 months after kidney transplant,
- Objective 2 : The percentage of patients dependent on dialysis and / or with an estimated GFR <20 mL / min / 1.73m² at 3 months
- Objective 3 : The vital status of kidney recipients from these donors at 3 months
- Objective 4 : The vital status of kidney recipients from these donors and serum creatinine (in μmol / L) with estimation of the glomerular filtration rate (GFR) according to CKD-EPI (in mL / min / 1.73m2), 1 year, 3 years, and 10 years from transplant.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
SOLUDACTONE 200 mg, lyophilisat et solution pour usage parentéral
PRD499841 · Product
- Active substance
- Potassium Canrenoate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 400 mg milligram(s)
- Max total dose
- 400 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- C03DA02 — POTASSIUM CANRENOATE
- Marketing authorisation
- 34009 325 225 1 4
- MA holder
- PFIZER HOLDING FRANCE
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
CHLORURE DE SODIUM 0,9 % BAXTER, solution pour perfusion en poche
PRD367015 · Product
- Active substance
- Sodium Chloride
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 1.8 g gram(s)
- Max total dose
- 1.8 g gram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B05XA03 — SODIUM CHLORIDE
- Marketing authorisation
- 34009 351 879 5 6
- MA holder
- BAXTER SAS
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
CHRU De Nancy
- Sponsor organisation
- CHRU De Nancy
- Address
- Co N°34, 29 Avenue Du Mal De Lattre De Tassigny, Bp 60034 29 Avenue Du Mal De Lattre De Tassigny Bp 60034
- City
- Nancy Cedex
- Postcode
- 54035
- Country
- France
Scientific contact point
- Organisation
- CHRU De Nancy
- Contact name
- Philippe GUERCI
Public contact point
- Organisation
- CHRU De Nancy
- Contact name
- Philippe GUERCI
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ongoing, recruiting | 36 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
CHRU De Nancy
Département d’Anesthésie-Réanimation et Médecine Périopératoire, Rue Du Morvan, 54500, Vandoeuvre Les Nancy
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| France | 2024-08-27 | 2024-08-27 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 5 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2024-513809-31-00 | 2 |
| Recruitment arrangements (for publication) | Aspect evalue et autorise sous directive | 1 |
| Subject information and informed consent form (for publication) | L_SIS and ICF_2024-513809-31-00 | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_SOLUDACTONE | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_2024-513809-31-00 | 2 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-07-26 | France | Acceptable 2024-08-26
|
2024-08-27 |