Effect of Low-dose Arginine-vasopressin Supplementation on Post-transplant Acute Kidney Injury After Liver Transplantation
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 304
- 试验地点
- 1
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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
干预措施: Arginine vasopressin (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.
干预措施: Norepinephrine (Drug)
结局指标
主要结局
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.
时间窗: 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.
次要结局
- 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 Number of AKI KDIGO 3(during the first 7 postoperative)
- To compare into the two arms the number of the Number of AKI KDIGO 1(1 during the first 7days)
- 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)
- Mortality(at 30 days)
- To compare into the two arms the Number of AKI KDIGO 2(during the first 7 postoperative)
- Average intraoperative norepinephrine concentrations(intraoperative)
- Number of platelets transfused intraoperatively(during the first 12 hours postoperatively.)
- Average intraoperative concentrations of other vasopressors and inotropes (Adrenalin, Dobutamine)(intraoperative)
- Amount of vascular filling solutions intraoperatively(During the first 12 hours postoperatively.)
- Number of days alive outside intensive care unit(during the 30 day post-operation)
- Sequential Organ Failure Assessment (SOFA score)(On the third and seventh postoperative day)