Low-dose Arginine-vasopressin Supplementation on Post-transplant Acute Kidney Injury After Liver Transplantation (AVENIR Trial)

February 3, 2026 updated by: Assistance Publique - Hôpitaux de Paris

Effect of Low-dose Arginine-vasopressin Supplementation on Post-transplant Acute Kidney Injury After Liver Transplantation

Liver transplantation (LT) is a high-risk surgery for hemodynamic instability and haemorrhagic shock with a high-risk of acute kidney injury (AKI). Indeed, the incidence of post-transplant AKI exceeds 50% in some series with 15% of patients requiring renal replacement therapy. Acute kidney injury after LT is a predisposing factor for chronic renal failure which is independently associated with higher morbidity and mortality.

Arginine vasopressin (AVP), an essential stress hormone released in response to hypotension, binds to AVPR1a to promote vasoconstriction. Furthermore, it may have nephroprotective effects with a preferential vasoconstriction of the post-glomerular arteriole resulting in increased glomerular filtration

The hypothesis of the present work is that low-dose arginine-vasopressin supplementation reduce posttransplant AKI in liver transplantation.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Prospective, national multicenter, double-blinded, randomized , controlled superiority trial with two parallel arms : AVP vs Norepinephrine

The primary objective is to demonstrate that intraoperative low-dose supplementation of AVP induces a reduction in posttransplant AKI after liver transplantation

Investigational medicinal product: vasopressin will be administered by continuous infusion. AVP will be used to a final concentration of 0.12 U/ml. The vasopressor infusion will be titrated to maintain an MAP of at least 65 mmHg. The study-drug infusion will be started at 5 ml/h and increased by 2.5 ml/h to achieve a maximum target rate of 30 ml/h, so that AVP doses ranged from 0.01 to 0.06 U/min.

Comparator treatment : norepinephrine will be administered by continuous infusion. Norepinephrine will be used with final concentrations of 120 microg/ml. The vasopressor infusion will be titrated to maintain an MAP of at least 65 mmHg. The study-drug infusion will be started at 5 ml/h and increased by 2.5 ml/h to achieve a maximum target rate of 30 ml/h, so that NE doses ranged from10 to 60 microg/min.

Study Type

Interventional

Enrollment (Estimated)

304

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Paris, France, 75010
        • Recruiting
        • URC Lariboisière-Fernand Widal-saint Louis
        • Principal Investigator:
          • Jaques DURANTEAU, Pr
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arginine vasopressin
low-dose arginine-vasopressin supplementation group: Vasopressin will be administered by continuous infusion. AVP will be used to a final concentration of 0.12 U/ml. The vasopressor infusion will be titrated to maintain an MAP of at least 65 mmHg. The study-drug infusion will be started at 5 ml/h and increased by 2.5 ml/h to achieve a maximum target rate of 30 ml/h, so that AVP doses ranged from 0.01 to 0.06 U/min
Drug: Arginine vasopressin
low-dose arginine-vasopressin supplementation group: Vasopressin will be administered by continuous infusion. AVP will be used to a final concentration of 0.12 U/ml. The vasopressor infusion will be titrated to maintain an MAP of at least 65 mmHg. The study-drug infusion will be started at 5 ml/h and increased by 2.5 ml/h to achieve a maximum target rate of 30 ml/h, so that AVP doses ranged from 0.01 to 0.06 U/min.
Active Comparator: Norepinephrine
Norepinephrine will be administered by continuous infusion. Norepinephrine will be used with final concentrations of 120 microg/ml. The vasopressor infusion will be titrated to maintain an MAP of at least 65 mmHg. The study-drug infusion will be started at 5 ml/h and increased by 2.5 ml/h to achieve a maximum target rate of 30 ml/h, so that NE doses ranged from10 to 60 microg/min.
Drug: Norepinephrine
Norepinephrine will be administered by continuous infusion. Norepinephrine will be used with final concentrations of 120 microg/ml. The vasopressor infusion will be titrated to maintain an MAP of at least 65 mmHg. The study-drug infusion will be started at 5 ml/h and increased by 2.5 ml/h to achieve a maximum target rate of 30 ml/h, so that NE doses ranged from10 to 60 microg/min.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The primary objective is to compare the effect of intraoperative low-dose supplementation of AVP vs norepinephrine infusions on post-transplant Acute Kidney Injury after liver transplantation.
Time Frame: during the first 7 postoperative days
The stages of AKI according to AKI Network criteria (KDIGO score) determined by changes in serum creatinine and changes in urine output.
during the first 7 postoperative days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: at 30 days
at 30 days
To compare into the two arms the number of packed red blood cellsand fresh frozen plasma transfused
Time Frame: during the first 12 hours postoperatively
during the first 12 hours postoperatively
To compare into the two arms the number of the Number of AKI KDIGO 1
Time Frame: 1 during the first 7days
defined as increase in serum creatinine concentration by 1.5 to 1.9 fold or ≥0.3mg/dl (or 27 micromol/L) within 48h or urine output <0.5 ml/Kg/h over a period 6-12 h)
1 during the first 7days
To compare into the two arms the Number of AKI KDIGO 2
Time Frame: during the first 7 postoperative
defined as increase in serum creatinine concentration by 2.0 to 2.9 fold or urine output <0.5 ml/Kg/h over a period ≥12 h)
during the first 7 postoperative
To compare into the Number of AKI KDIGO 3
Time Frame: during the first 7 postoperative
defined as increase in serum creatinine concentration ≥ 3 fold or ≥ 4mg/dl (or 354 micromol/L) or urine output <0.3 ml/Kg/h for ≥24h or anuria>12h)
during the first 7 postoperative
The need for renal replacement for replacement therapy (RRT) in ICU
Time Frame: during the first 7 days postoperatively and on postoperative day 30
during the first 7 days postoperatively and on postoperative day 30
The number of patients remaining on dialysis at the end of the study
Time Frame: on the 30th Day
on the 30th Day
Average intraoperative norepinephrine concentrations
Time Frame: intraoperative
intraoperative
Average intraoperative concentrations of other vasopressors and inotropes (Adrenalin, Dobutamine)
Time Frame: intraoperative
intraoperative
Number of platelets transfused intraoperatively
Time Frame: during the first 12 hours postoperatively.
during the first 12 hours postoperatively.
Amount of vascular filling solutions intraoperatively
Time Frame: During the first 12 hours postoperatively.
During the first 12 hours postoperatively.
Sequential Organ Failure Assessment (SOFA score)
Time Frame: On the third and seventh postoperative day

Sequential Organ Failure Assessment (SOFA score between 0 and 24). Zero indicates that the patient has no organ dysfunction, twenty-four is the maximum score and indicates that the patient has vinght four is the maximum score and indicates that the patient has all 6 of the organ dysfunctions explored.

(respiratory, coagulatory, liver, cardiovascular, renal, and neurologic)
On the third and seventh postoperative day
Number of days alive outside intensive care unit
Time Frame: during the 30 day post-operation
during the 30 day post-operation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Study Director: Jacques DURANTEAU, Pr, Département Anesthésie-Réanimation - Université Paris-Saclay Hospital Bicêtre - Paul Brousse
  • Principal Investigator: Gilles LEBUFFE, Pr, Service Anesthésie-Réanimation - CHU de Lille
  • Principal Investigator: Daniel EYRAUD, Pr, Service Anesthésie-Réanimation -APHP Pitié-Salpêtrière
  • Principal Investigator: Emmanuel WEISS, Pr, Service Anesthésie-Réanimation - APHP hôpital Beaujon
  • Principal Investigator: Antoine DEWITTE, Pr, Service Anesthésie-Réanimation -CHU de Bordeaux centre médicochirurgical Magellan hôpital Haut Lévêque
  • Principal Investigator: Baptiste LORDIER, Pr, Service Anesthésie-Réanimation -CHU de Strasbourg Hôpital de Hautepierre
  • Principal Investigator: Alice BLET, Pr, Service Anesthésie-Réanimation - Hôpital de la Croix Rousse

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 16, 2025

Primary Completion (Actual)

May 16, 2025

Study Completion (Estimated)

May 16, 2027

Study Registration Dates

First Submitted

February 23, 2024

First Submitted That Met QC Criteria

March 27, 2024

First Posted (Actual)

April 3, 2024

Study Record Updates

Last Update Posted (Actual)

February 5, 2026

Last Update Submitted That Met QC Criteria

February 3, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APHP220827

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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