Clinical trial NCT06344442: Low-dose Arginine-vasopressin Supplementation on Post-transplant Acute Kidney Injury After Liver Transplantation (AVENIR Trial)
Official title: Effect of Low-dose Arginine-vasopressin Supplementation on Post-transplant Acute Kidney Injury After Liver Transplantation
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Acute Kidney Injury Post Liver Transplantation
Keywords: Low dose arginine -vasopressin Acute Kidney injury Liver transplantation
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2024-04-03
Enrollment: 304
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, national multicentre, double-blinded, randomized ,controlled superiority trial with two parallel arms
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: during the first 7 postoperative days
Secondary outcomes:
measure: To compare into the two arms the number of packed red blood cellsand fresh frozen plasma transfused
timeFrame: during the first 12 hours postoperatively
measure: To compare into the two arms the number of the Number of AKI KDIGO 1
timeFrame: 1 during the first 7days
measure: To compare into the two arms the Number of AKI KDIGO 2
timeFrame: during the first 7 postoperative
measure: To compare into the Number of AKI KDIGO 3
timeFrame: during the first 7 postoperative
measure: The need for renal replacement for replacement therapy (RRT) in ICU
timeFrame: during the first 7 days postoperatively and on postoperative day 30
measure: The number of patients remaining on dialysis at the end of the study
timeFrame: on the 30th Day
measure: Average intraoperative norepinephrine concentrations
timeFrame: intraoperative
measure: Average intraoperative concentrations of other vasopressors and inotropes (Adrenalin, Dobutamine)
timeFrame: intraoperative
measure: Number of platelets transfused intraoperatively
timeFrame: during the first 12 hours postoperatively.
measure: Amount of vascular filling solutions intraoperatively
timeFrame: During the first 12 hours postoperatively.
measure: Sequential Organ Failure Assessment (SOFA score)
timeFrame: On the third and seventh postoperative day
measure: Number of days alive outside intensive care unit
timeFrame: during the 30 day post-operation
measure: Mortality
timeFrame: at 30 days
Other outcomes:
Locations:
city: Paris
country: France
facility: URC Lariboisière-Fernand Widal-saint Louis
Study officials:
affiliation: Département Anesthésie-Réanimation - Université Paris-Saclay Hospital Bicêtre - Paul Brousse
name: Jacques DURANTEAU, Pr
role: STUDY_DIRECTOR
affiliation: Service Anesthésie-Réanimation - CHU de Lille
name: Gilles LEBUFFE, Pr
role: PRINCIPAL_INVESTIGATOR
affiliation: Service Anesthésie-Réanimation -APHP Pitié-Salpêtrière
name: Daniel EYRAUD, Pr
role: PRINCIPAL_INVESTIGATOR
affiliation: Service Anesthésie-Réanimation - APHP hôpital Beaujon
name: Emmanuel WEISS, Pr
role: PRINCIPAL_INVESTIGATOR
affiliation: Service Anesthésie-Réanimation -CHU de Bordeaux centre médicochirurgical Magellan hôpital Haut Lévêque
name: Antoine DEWITTE, Pr
role: PRINCIPAL_INVESTIGATOR
affiliation: Service Anesthésie-Réanimation -CHU de Strasbourg Hôpital de Hautepierre
name: Baptiste LORDIER, Pr
role: PRINCIPAL_INVESTIGATOR
affiliation: Service Anesthésie-Réanimation - Hôpital de la Croix Rousse
name: Alice BLET, Pr
role: PRINCIPAL_INVESTIGATOR
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