Somatostatin as Inflow Modulator in Adult-to-adult Living Donor Liver Transplantation: a Randomized, Double-blind, Placebo-controlled Trial
试验速览
- 阶段
- 4 期
- 入组人数
- 56
- 主要终点
- Portal venous flow changes
研究概览
简要总结
Aim of the study is to investigate the safety and the efficacy of somatostatin as liver inflow modulator in patients with end-stage liver disease (ESLD) and clinically significant portal hypertension (CSPH) undergoing Adult-to-Adult living donor liver transplantation (A2ALDLT).
详细描述
In liver transplantation (LT) portal hyperperfusion can severely impair graft function and survival, mainly in cases of partial LT. Perioperative somatostatin infusion has been shown to be safe, to reduce the Hepatic Vein to Portal Vein Gradients and to preserve the arterial inflow to the graft in whole liver transplantation. In partial grafts, the pharmacological action of somatostatin could reduce the graft damage due to portal hyperperfusion and arterial hypoperfusion, reducing the incidence of small-for-size syndrome and graft loss and improving the patients survival.
Objective of the study is to investigate the safety and the efficacy of somatostatin as liver inflow modulator in patients with end-stage liver disease (ESLD) and clinically significant portal hypertension (CSPH) undergoing Adult-to-Adult living donor liver transplantation (A2ALDLT).
Fifty-six patients undergoing A2ALDLT for ESLD and CSPH will be randomized double-blindly to receive somatostatin or placebo (1:1). The study drug will be administered intraoperatively as 5ml bolus (somatostatin: 500 μg), followed by a 2.5 ml/hour infusion (somatostatin: 250 μg/hour) for 10 days. Hepatic and systemic hemodynamic will be measured, along with liver function tests and clinical outcomes. The ischemia-reperfusion injury (IRI) will be analysed through histological and protein expression analysis.
The primary endpoint of the study will be the portal vein flow reduction measured at the end of liver transplant. Secondary end-points will be the reduction in the portal vein pressure, the rate of patients requiring surgical inflow modulation, the incidence of small for size syndrome, the severity of the ischemia reperfusion injury, the need for early re-transplantation (6 months), the incidence of adverse and serious adverse events, the 90-day mortality.
This randomized controlled trial could be the first to show the efficacy of somatostatin as modulator of the graft inflow in living-donor liver transplantation and potential improvement in graft and patient survival.
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)
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
- •Adult patients (> 18 years old) undergoing Adult-to-Adult Living donor Liver Transplantation (LDLT) (right or left lobe)
- •Indication for LDLT: End Stage Liver Disease with Portal Hypertension (HVPG ≥ 10mmHg)
排除标准
- •Complete portal vein thrombosis (pre-operative or intraoperative diagnosis)
- •Hepatopulmonary hypertension
- •Adult-to-Adult Living donor liver transplantation for Fulminant hepatic failure
- •Recipients of multiple solid organ transplants
- •History of cardiac arrhythmias
研究组 & 干预措施
Somatostatin
干预措施: Somatostatin (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Portal venous flow changes
时间窗: Day 0 - At the end of liver transplantation surgery, before skin closure
Flow measured with transit time flow measurement system
次要结局
- Rate of patients presenting a significant portal venous flow reduction (-20%)(Day 0 - At the end of liver transplantation surgery, before skin closure)
- Mortality(90 days)
- Rate of patients requiring surgical inflow modulation(Day 0 - At the end of liver transplantation surgery, before skin closure)
- Rates of patients requiring early re-transplantation(6 months)
- Changes in hepatic artery flow(Day 0 - At the end of liver transplantation surgery, before skin closure)
- Incidence of Small-for-size syndrome(30 days)
- Changes in postoperative portal venous flow(Postoperative day 1, 7 and 14)
- Incidence of adverse and serious adverse events(18 months)
研究者
Roberto Troisi
Principal Investigator, Clinical Professor
King Faisal Specialist Hospital & Research Center