Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
304
Countries
1
Sites
9
Acute Kidney Injury
To demonstrate that intraoperative low-dose supplementation of AVP induces a reduction in post-transplant AKI after liver transplantation.
Key facts
- Sponsor
- Assistance Publique Hopitaux De Paris
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13], Diseases [C] - Digestive System Diseases [C06], Diseases [C] - Male Urogenital Diseases [C12]
- Trial duration
- 16 Apr 2025 → ongoing
- Decision date (initial)
- 2024-01-12
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- DGOS - French Ministry of Health · AMOMED
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
To demonstrate that intraoperative low-dose supplementation of AVP induces a reduction in post-transplant AKI after liver transplantation.
Secondary objectives 1
- To compare the two arms in terms of number of packed red blood cells, platelets and fresh frozen plasma, vascular filling solutions transfused intraoperatively and during the first 12 hours postoperatively, need for renal replacement for replacement therapy (RRT) in ICU, average intraoperative norepinephrine and other vasopressors and inotropes concentrations sequential Organ Failure Assessment (SOFA score) on the third postoperative day length of stay in intensive care unit, and mortality at 30 days
Conditions and MedDRA coding
Acute Kidney Injury
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.1 | LLT | 10000821 | Acute kidney failure | 10038359 |
| 21.0 | LLT | 10024716 | Liver transplantation | 10042613 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- Age ≥ 18 years
- Any adult patient with a scheduled liver transplantation
- All participants will need to be given clear information about the study and give signed informed consent
- Person affiliated to the Social Security
Exclusion criteria 10
- Super-emergency for liver transplantation or fulminant hepatitis
- Patient listed for or receiving simultaneous liver-kidney transplantation (SLKT)
- Patients with end-stage renal disease (chronic eGFR < 15 mL/min/1.73 m2 or requiring extra-renal purification before liver transplantation
- Patient with epilepsy
- Hypersensitivity to arginine-vasopressin and to its excipients
- Patient refusal
- Patients for whom it is impossible to give informed consent (language barrier)
- Adults under guardianship or trusteeship, persons deprived of their liberty
- Patient enrolled in another interventional clinical study
- Pregnancy or breastfeeding
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Stages of AKI according to AKI Network criteria (KDIGO score) during the first 7 postoperative days
Secondary endpoints 9
- The number of packed red blood cells and fresh frozen plasma transfused intraoperatively and during the first 12 hours postoperatively
- The need for renal replacement for replacement therapy (RRT) in ICU
- Average intraoperative norepinephrine concentrations
- Average intraoperative concentrations of other vasopressors and inotropes (Adrenalin, Dobutamine)
- Number of platelets transfused intraoperatively and during the first 12 hours postoperatively
- Amount of vascular filling solutions intraoperatively and during the first 12 hours postoperatively
- Sequential Organ Failure Assessment (score SOFA) on the third postoperative day
- Number of days alive outside intensive care unit during the 30 day post-operation
- Mortality at 30 days
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
REVERPLEG 40 U.I./2 mL, solution à diluer pour perfusion
PRD6353881 · Product
- Active substance
- Argipressin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 86.4 U unit(s)
- Max total dose
- 86.4 U unit(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- H01BA01 — VASOPRESSIN
- Marketing authorisation
- 34009 550 556 4 8
- MA holder
- ORPHA-DEVEL HANDELS UND VERTRIEBS GMBH
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 1
NORADRENALINE VIATRIS 2 mg/ml SANS SULFITES, solution à diluer pour perfusion
PRD9747470 · Product
- Active substance
- Noradrenaline Tartrate
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 40 mg milligram(s)
- Max total dose
- 40 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- C01CA03 — NOREPINEPHRINE
- Marketing authorisation
- NL27494
- MA holder
- VIATRIS SANTE
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Assistance Publique Hopitaux De Paris
- Sponsor organisation
- Assistance Publique Hopitaux De Paris
- Address
- Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux
- City
- Paris Cedex 10
- Postcode
- 75475
- Country
- France
Scientific contact point
- Organisation
- Assistance Publique Hopitaux De Paris
- Contact name
- Pr Jacques DURANTEAU
Public contact point
- Organisation
- Assistance Publique Hopitaux De Paris
- Contact name
- Pr Jacques DURANTEAU
Locations
1 EU/EEA country · 9 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ongoing, recruiting | 304 | 9 |
| Rest of world | — | 0 | — |
Investigational sites
Centre Hospitalier Regional Universitaire De Tours
Anesthésie-Réanimation, Avenue De La Republique, 37170, Chambray Les Tours
Les Hopitaux Universitaires De Strasbourg
Anesthésie-Réanimation, 1 Avenue Moliere, Bp 49, Strasbourg Cedex 2
Centre Hospitalier Universitaire De Lille
Anesthésie-Réanimation, Rue Michel Polonovski, 59037, Lille Cedex
Hospices Civils De Lyon
Anesthésie-Réanimation, 103 Grande Rue De La Croix Rousse, 69317, Lyon Cedex 04
University Hospital Of Clermont-Ferrand
Anesthésie-Réanimation, 1 Place Lucie Et Raymond Aubrac, 63100, Clermont-Ferrand
Centre Hospitalier Universitaire De Bordeaux
Anesthésie-Réanimation, Avenue De Magellan, 33600, Pessac
Assistance Publique Hopitaux De Paris
Anesthésie-Réanimation, Num Voie 47 A 83, 47 Boulevard De L Hopital, Paris
Assistance Publique Hopitaux De Paris
Anesthésie-Réanimation, 12 Avenue Paul Vaillant Couturier, 94800, Villejuif
Assistance Publique Hopitaux De Paris
Anesthésie-Réanimation, 100 Boulevard Du General Leclerc, 92110, Clichy
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 | 2025-04-16 | 2025-04-16 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 11 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Pregnancy notification form 2023-506512-40-00 | 1-0 |
| Protocol (for publication) | D1_Protocol 2023-506512-40-00_public | 3.0 |
| Protocol (for publication) | D1_SAE notification form 2023-506512-40-00 | 1-0 |
| Protocol (for publication) | D1_SAE notification form annex 2023-506512-40-00 | 1-0 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adults | 1-2 |
| Subject information and informed consent form (for publication) | L1_SIS-simplified for patients awaiting transplants | 1.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information description_Patient Card | 1-0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Noradrenaline | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC REVERPLEG | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_FR 2023-506512-40-00 | 2.0 |
Application history
7 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-10-02 | France | Acceptable 2024-01-11
|
2024-01-12 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-05-31 | France | Acceptable | 2024-06-17 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-02-19 | France | Acceptable | 2025-03-13 |
| 4 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-05-14 | |||
| 5 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-05-26 | France | Acceptable | 2025-06-11 |
| 6 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-10-29 | France | Acceptable 2025-12-15
|
2025-12-19 |
| 7 | SUBSTANTIAL MODIFICATION | SM-6 | 2026-04-21 | France | Acceptable 2026-05-12
|
2026-05-19 |