Effects of an Intraoperative Low-splanchnic Blood Volume Restrictive Fluid Management Strategy Compared to a Cardiac Output Optimized Liberal Fluid Management Strategy on Postoperative Outcomes in Liver Transplantation: A Pilot Multicenter Randomized Controlled Trial (REFIL-1)
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 138
- 试验地点
- 4
- 主要终点
- Adherence
研究概览
简要总结
Hypothesis: A Canadian multicentre clinical trial is feasible. Study Design: Multicenter internal pilot parallel arm randomized controlled trial.
Study population: Patients with end-stage liver disease (ESLD) undergoing a liver transplantation, not meeting any exclusion criteria.
Primary feasibility endpoint: An overall recruitment rate ≥ 4 patients/month across all four participating sites.
Secondary feasibility endpoints: A protocol adherence > 90%, a 30-day (or hospital discharge) and 6-month outcome measurement > 90%, and a mean difference in total intraoperative volume received (crystalloids and colloids combined) > 1000 ml between groups.
Study intervention: Low splanchnic blood volume restrictive fluid management strategy (intervention). A phlebotomy, performed prior to dissection and transfused back after graft reperfusion, combined with a hemodynamic goal-directed restrictive fluid management strategy.
Optimized cardiac-output liberal fluid management strategy (control) A hemodynamic goal-directed liberal fluid management strategy that optimizes cardiac output throughout surgery.
详细描述
MAIN OBJECTIVE The main objective of the REFIL-1 pilot study is to establish the feasibility (recruitment, adherence, outcome measurement) of conducting a Canadian multicentre randomized controlled trial comparing an intraoperative low-splanchnic blood volume restrictive fluid management strategy to a cardiac output optimised liberal fluid management strategy in adult liver transplantation (LT) for ESLD. The hypothesis is that a Canadian multicentre clinical trial is feasible.
SECONDARY OBJECTIVES The overarching objective of the REFIL (Restrictive Fluid management In Liver transplantation) research program, which will be answered in a future large-scale trial, regards the efficacy of the proposed interventional strategy to improve postoperative outcomes in LT.
TERTIARY OBJECTIVES Our tertiary objective is to measure the cost-effectiveness of the proposed intervention based on the composite outcome of any severe postoperative complications and graft loss.
DESIGN AND STUDY POPULATION This study is a multicentre internal pilot parallel arm randomized trial comparing two intraoperative hemodynamic and splanchnic blood volume management strategies in LT recipients.
This study is conducted in two phases: a pilot phase, which demonstrated feasibility across Canada, followed by a larger-scale phase (the efficacy phase).
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Only the anesthesiology team will know the allocation received, as they must implement the intervention, thereby limiting differential outcome classification bias because they will not assess outcomes. Patients, surgeons, and non-anesthesia health professionals will be blinded to the allocation.
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
- •Any adult patient ≥ 18 years of age undergoing liver transplantation for ESLD.
排除标准
- •Patients undergoing LT for an indication other than ESLD such as acute liver failure, liver cancer without ESLD, retransplantation, amyloid neuropathy or any other indication not associated with ESLD.
- •Patients undergoing a combined liver and lung or liver and heart transplantation.
- •Patients with any of the following conditions:
- •severe chronic renal failure (GFR < 15 ml/minute/1.73 m2 [CKD-EPI equation] or already on RRT);
- •severe anemia (hemoglobin level < 80 g/L);76,93,109
- •hemodynamic instability (norepinephrine equivalent > 10 ug/min).
研究组 & 干预措施
Restrictive group - Low splanchnic blood volume Restrictive fluid management strategy
This strategy first consists of performing a phlebotomy without fluid replacement at the start of surgery. Fluids are restricted to prevent excessive fluid administration and its effects on splanchnic blood volume and blood loss, in addition to the effects of phlebotomy, and to limit fluid overload. Fluids are administered to compensate for blood loss and treat severe hemodynamic instability. The blood collected by phlebotomy is transfused back at the beginning of the reperfusion phase, where fluid management will be based on goal-directed therapy (GDT) using either Pulse Pressure Variation (PPV) or Stroke Volume (SV), as in the control group.
干预措施: Phlebotomy (Procedure)
Restrictive group - Low splanchnic blood volume Restrictive fluid management strategy
This strategy first consists of performing a phlebotomy without fluid replacement at the start of surgery. Fluids are restricted to prevent excessive fluid administration and its effects on splanchnic blood volume and blood loss, in addition to the effects of phlebotomy, and to limit fluid overload. Fluids are administered to compensate for blood loss and treat severe hemodynamic instability. The blood collected by phlebotomy is transfused back at the beginning of the reperfusion phase, where fluid management will be based on goal-directed therapy (GDT) using either Pulse Pressure Variation (PPV) or Stroke Volume (SV), as in the control group.
干预措施: Low splanchnic blood volume restrictive fluid management strategy (Procedure)
Liberal group - Optimized cardiac output liberal fluid management strategy
This strategy involves administering 250 ml fluid boluses until SV stops increasing by more than 10% or until PPV is below 12%.
干预措施: Optimized cardiac output liberal fluid management strategy (Procedure)
结局指标
主要结局
Adherence
时间窗: At time of surgery
Protocol adherence \> 90%, determined using a questionnaire
Mean difference in total volume received
时间窗: At time of surgery
A mean difference in total volume received (crystalloids and colloids combined) \> 1000 ml between groups.
Hospital outcome measurement completeness
时间窗: At 30 days (or hospital discharge) after surgery
A 30 days or hospital discharge outcome measurement \> 90%
6-month outcome measurement completeness
时间窗: 6 months after surgery
6-month outcome measurement \> 90%
Recruitment rate
时间窗: 36 months (at study level)
Overall recruitment rate ≥ 4 patients/month (across all sites)
次要结局
- Intraoperative blood loss(End of surgery)
- Intraoperative and perioperative blood product transfusions(From randomization up to 30 days or hospital discharge, whichever comes first)
- Any other severe complication(From randomization up to 30 days or hospital discharge, whichever comes first)
- Intensive care unit (ICU) length of stay(From randomization up to hospital discharge (ascertained up to end of follow-up at 1 year))
- Quality of life (QoL)(6 & 12 months after surgery)
- Graft complications(From randomization up to 1 year after surgery)
- Severe complications and graft lost(Up to 30 days or hospital discharge)
- 7-day quality of recovery(7 days after surgery)
- 7-day graft dysfunction(7 days after surgery)
- Organ dysfunction and support(30 days)
- Hospital length of stay(From randomization up to hospital discharge (ascertained up to end of follow-up at 1 year))
- Any complication(From randomization up to 30 days or hospital discharge, whichever comes first)
- Hospital readmissions(From randomization up to 1 year after surgery)
- Survival(From randomization up to 1 year after surgery)
- 7-day AKI (grade 2 or 3)(7 days after surgery)