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

NCT06344442 | Recruiting Phase 3 DMC

• 1 other identifier: APHP220827
• Study Type: interventional
• Target: 304
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Kidney Injury Post Liver Transplantation

Keywords

Low dose arginine -vasopressin Acute Kidney injury Liver transplantation

Outcome Measures

Primary Outcomes (1)

• 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.

  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 Outcomes (13)

• To compare into the two arms the number of packed red blood cellsand fresh frozen plasma transfused

  during the first 12 hours postoperatively

• To compare into the two arms the number of the Number of AKI KDIGO 1

  1 during the first 7days

• To compare into the two arms the Number of AKI KDIGO 2

  during the first 7 postoperative

• To compare into the Number of AKI KDIGO 3

  during the first 7 postoperative

• The need for renal replacement for replacement therapy (RRT) in ICU

  during the first 7 days postoperatively and on postoperative day 30

Study Arms (2)

Arginine vasopressin

EXPERIMENTAL

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

Norepinephrine

ACTIVE COMPARATOR

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

Interventions

Arginine vasopressin DRUG

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.

Arginine vasopressin

Norepinephrine DRUG

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.

Norepinephrine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

URC Lariboisière-Fernand Widal-saint Louis

Paris, 75010, France

RECRUITING

Related Publications (13)

• Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996 Jul;22(7):707-10. doi: 10.1007/BF01709751. No abstract available.

  PMID: 8844239 BACKGROUND

• Hilmi IA, Damian D, Al-Khafaji A, Planinsic R, Boucek C, Sakai T, Chang CC, Kellum JA. Acute kidney injury following orthotopic liver transplantation: incidence, risk factors, and effects on patient and graft outcomes. Br J Anaesth. 2015 Jun;114(6):919-26. doi: 10.1093/bja/aeu556. Epub 2015 Feb 10.

  PMID: 25673576 RESULT

• Watt KD, Pedersen RA, Kremers WK, Heimbach JK, Charlton MR. Evolution of causes and risk factors for mortality post-liver transplant: results of the NIDDK long-term follow-up study. Am J Transplant. 2010 Jun;10(6):1420-7. doi: 10.1111/j.1600-6143.2010.03126.x. Epub 2010 May 10.

  PMID: 20486907 RESULT

• Hajjar LA, Vincent JL, Barbosa Gomes Galas FR, Rhodes A, Landoni G, Osawa EA, Melo RR, Sundin MR, Grande SM, Gaiotto FA, Pomerantzeff PM, Dallan LO, Franco RA, Nakamura RE, Lisboa LA, de Almeida JP, Gerent AM, Souza DH, Gaiane MA, Fukushima JT, Park CL, Zambolim C, Rocha Ferreira GS, Strabelli TM, Fernandes FL, Camara L, Zeferino S, Santos VG, Piccioni MA, Jatene FB, Costa Auler JO Jr, Filho RK. Vasopressin versus Norepinephrine in Patients with Vasoplegic Shock after Cardiac Surgery: The VANCS Randomized Controlled Trial. Anesthesiology. 2017 Jan;126(1):85-93. doi: 10.1097/ALN.0000000000001434.

  PMID: 27841822 RESULT

• Pecci A, Balduini CL. Desmopressin and super platelets. Blood. 2014 Mar 20;123(12):1779-80. doi: 10.1182/blood-2014-01-551242. No abstract available.

  PMID: 24652962 RESULT

• Sims CA, Holena D, Kim P, Pascual J, Smith B, Martin N, Seamon M, Shiroff A, Raza S, Kaplan L, Grill E, Zimmerman N, Mason C, Abella B, Reilly P. Effect of Low-Dose Supplementation of Arginine Vasopressin on Need for Blood Product Transfusions in Patients With Trauma and Hemorrhagic Shock: A Randomized Clinical Trial. JAMA Surg. 2019 Nov 1;154(11):994-1003. doi: 10.1001/jamasurg.2019.2884.

  PMID: 31461138 RESULT

• Okazaki N, Iguchi N, Evans RG, Hood SG, Bellomo R, May CN, Lankadeva YR. Beneficial Effects of Vasopressin Compared With Norepinephrine on Renal Perfusion, Oxygenation, and Function in Experimental Septic Acute Kidney Injury. Crit Care Med. 2020 Oct;48(10):e951-e958. doi: 10.1097/CCM.0000000000004511.

  PMID: 32931198 RESULT

• Russell JA, Walley KR, Singer J, Gordon AC, Hebert PC, Cooper DJ, Holmes CL, Mehta S, Granton JT, Storms MM, Cook DJ, Presneill JJ, Ayers D; VASST Investigators. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008 Feb 28;358(9):877-87. doi: 10.1056/NEJMoa067373.

  PMID: 18305265 RESULT

• Gordon AC, Russell JA, Walley KR, Singer J, Ayers D, Storms MM, Holmes CL, Hebert PC, Cooper DJ, Mehta S, Granton JT, Cook DJ, Presneill JJ. The effects of vasopressin on acute kidney injury in septic shock. Intensive Care Med. 2010 Jan;36(1):83-91. doi: 10.1007/s00134-009-1687-x. Epub 2009 Oct 20.

  PMID: 19841897 RESULT

• Gordon AC, Mason AJ, Thirunavukkarasu N, Perkins GD, Cecconi M, Cepkova M, Pogson DG, Aya HD, Anjum A, Frazier GJ, Santhakumaran S, Ashby D, Brett SJ; VANISH Investigators. Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial. JAMA. 2016 Aug 2;316(5):509-18. doi: 10.1001/jama.2016.10485.

  PMID: 27483065 RESULT

• Edwards RM, Trizna W, Kinter LB. Renal microvascular effects of vasopressin and vasopressin antagonists. Am J Physiol. 1989 Feb;256(2 Pt 2):F274-8. doi: 10.1152/ajprenal.1989.256.2.F274.

  PMID: 2916660 RESULT

• Holmes CL, Patel BM, Russell JA, Walley KR. Physiology of vasopressin relevant to management of septic shock. Chest. 2001 Sep;120(3):989-1002. doi: 10.1378/chest.120.3.989.

  PMID: 11555538 RESULT

• Kellum JA, Lameire N; KDIGO AKI Guideline Work Group. Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1). Crit Care. 2013 Feb 4;17(1):204. doi: 10.1186/cc11454.

  PMID: 23394211 RESULT

MeSH Terms

Interventions

Arginine Vasopressin; Norepinephrine

Intervention Hierarchy (Ancestors)

Vasopressins; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Jacques DURANTEAU, Pr

  Département Anesthésie-Réanimation - Université Paris-Saclay Hospital Bicêtre - Paul Brousse

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jacques DURANTEAU, Pr

CONTACT

01 45 21 34 41; jacques.duranteau@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All the clinical teams involved intraoperatively (anaesthetists, nurse anaesthetists and surgeons) and postoperatively (doctors and nurses who will take care of the patient postoperatively) and the families will ignore the allocation of treatments for the duration of the trial,except the nurse in charge of preparing the infusions ,She will ensure respect for the blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, national multicentre, double-blinded, randomized ,controlled superiority trial with two parallel arms

Study Record Dates

• First Submitted: February 23, 2024
• First Posted: April 3, 2024
• Study Start: April 16, 2025
• Primary Completion: May 16, 2025
• Study Completion (Estimated): May 16, 2027
• Last Updated: February 5, 2026

Record last verified: 2026-02

Locations

FR (1)