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

Assistance Publique - Hôpitaux de Paris

Status and phase: Enrolling; Phase 3

Conditions: Acute Kidney Injury Post Liver Transplantation

Treatments: Drug: Arginine vasopressin; Drug: Norepinephrine

Study type: Interventional

Funder types: Other

Identifiers

NCT06344442

APHP220827

Details and patient eligibility

About

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.

Full 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.

Enrollment: 304 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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304 participants in 2 patient groups

Arginine vasopressin

Experimental group

Description:

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

Treatment:

Drug: Arginine vasopressin

Norepinephrine

Active Comparator group

Description:

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.

Treatment:

Drug: Norepinephrine