Acute Kidney Injury Post Liver Transplantation
Conditions
Keywords
Low dose arginine -vasopressin Acute Kidney injury Liver transplantation
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.
Interventions
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.
DRUGNorepinephrine
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.
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
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
Intervention model description
Prospective, national multicentre, double-blinded, randomized ,controlled superiority trial with two parallel arms
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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) |
| To compare into the two arms the Number of AKI KDIGO 2 | 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) |
| To compare into the Number of AKI KDIGO 3 | 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) |
| The need for renal replacement for replacement therapy (RRT) in ICU | during the first 7 days postoperatively and on postoperative day 30 | — |
| The number of patients remaining on dialysis at the end of the study | on the 30th Day | — |
| Average intraoperative norepinephrine concentrations | intraoperative | — |
| Average intraoperative concentrations of other vasopressors and inotropes (Adrenalin, Dobutamine) | intraoperative | — |
| Number of platelets transfused intraoperatively | during the first 12 hours postoperatively. | — |
| Amount of vascular filling solutions intraoperatively | During the first 12 hours postoperatively. | — |
| Sequential Organ Failure Assessment (SOFA score) | 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) |
| Number of days alive outside intensive care unit | during the 30 day post-operation | — |
| Mortality | at 30 days | — |
Countries
France
Contacts
CONTACTJacques DURANTEAU, Pr
STUDY_DIRECTORJacques DURANTEAU, Pr
Département Anesthésie-Réanimation - Université Paris-Saclay Hospital Bicêtre - Paul Brousse
PRINCIPAL_INVESTIGATORGilles LEBUFFE, Pr
Service Anesthésie-Réanimation - CHU de Lille
PRINCIPAL_INVESTIGATORDaniel EYRAUD, Pr
Service Anesthésie-Réanimation -APHP Pitié-Salpêtrière
PRINCIPAL_INVESTIGATOREmmanuel WEISS, Pr
Service Anesthésie-Réanimation - APHP hôpital Beaujon
PRINCIPAL_INVESTIGATORAntoine DEWITTE, Pr
Service Anesthésie-Réanimation -CHU de Bordeaux centre médicochirurgical Magellan hôpital Haut Lévêque
PRINCIPAL_INVESTIGATORBaptiste LORDIER, Pr
Service Anesthésie-Réanimation -CHU de Strasbourg Hôpital de Hautepierre
PRINCIPAL_INVESTIGATORAlice BLET, Pr
Service Anesthésie-Réanimation - Hôpital de la Croix Rousse
Outcome results
None listed