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 Multicenter Randomized Controlled Trial (REFIL-2)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 866
- 试验地点
- 4
- 主要终点
- Number of participants with at least one severe complication
研究概览
简要总结
The goal of the REFIL-2 study is to evaluate the effectiveness of a low splanchnic blood volume restrictive fluid management strategy (a strategy that involves limiting fluid administration and prioritizing the use of medications that raise blood pressure during surgery, combined with phlebotomy) in improving patients' recovery after surgery. The study compares the low splanchnic blood volume restrictive fluid management strategy to an optimized cardiac-output liberal fluid management strategy (which involves administering more fluids to raise blood pressure with less reliance on medications). Outcomes important to patients will be measured.
This study (REFIL-2) had a vanguard phase (internal pilot) that included 138 patients (NCT05647733). The patients included in the vanguard pilot phase were not compared between groups but only analyzed descriptively using aggregated data. Only feasibility metrics were compared (see NCT05647733). These 138 patients were thus rolled into the REFIL-2 trial and included in the final sample size reported herein.
详细描述
People with advanced liver disease have poor blood circulation, and too much blood accumulates in the abdomen (a condition known as high intra-abdominal blood volume). However, liver transplantation (LT) is a complex surgery during which the patient can lose a significant amount of blood and blood pressure can fluctuate widely. Therefore, restricting fluids and using medications to raise blood pressure is a strategy that could reduce blood loss and potentially also certain complications after surgery. Furthermore, phlebotomy appears to reduce intra-abdominal blood volume, blood loss, drops in blood pressure, and the need for red blood cell transfusions, potentially improving recovery after surgery. This study therefore aims to determine the best way to manage fluids during a liver transplantation by comparing these two care strategies. Another goal of the study is to measure the cost-effectiveness of the proposed intervention.
Hypothesis: An intraoperative low splanchnic blood volume restrictive fluid management strategy is superior to an optimized cardiac-output liberal fluid management strategy in reducing postoperative severe complications after liver transplantation
Design: Multicenter blinded parallel arm randomized controlled trial
Study population: Adult patients undergoing a liver transplantation for end-stage liver disease (ESLD)
All participants will be followed during their index hospitalization up to post-transplantation Day 30 (whichever comes first), and for 12 months post-transplantation to assess some clinical outcomes, quality of life (QoL), and survival (being alive beyond the index hospitalization).
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
- Double (Participant, Investigator)
盲法说明
Only the anesthesiology team will know which group the participant is assigned to, since they are responsible for implementing the intervention. They receive the allocated intervention by text message or email.
Patients, surgeons, non-anesthesia health professionals, and research staff involved in the study procedures and data collection will not know this information.
The primary outcome will be adjudicated by blinded adjudicators.
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 ≥ 18 years old
- •Undergoing liver transplantation (LT)
- •End-stage liver disease (ESLD) (with or without hepatocellular carcinoma) as the indication for transplantation.
排除标准
- •Undergoing LT for an indication other than ESLD (e.g., acute liver failure, primary liver cancer without ESLD, retransplantation, amyloid neuropathy, polycystic liver disease, or any other indication not associated with ESLD)
- •Undergoing combined solid organ transplantations
- •Any of the following conditions:
- •severe chronic renal failure (GFR < 15 ml/minute/1.73 m2 [CKD-EPI equation] or already on renal replacement therapy (RRT))
- •severe anemia (hemoglobin level < 80 g/L)
- •hemodynamic instability (norepinephrine equivalent > 10 ug/min)
- •Physician refusal to enroll the patient.
结局指标
主要结局
Number of participants with at least one severe complication
时间窗: Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first
Incidence of at least one severe complications defined as a complication of grade ≥ 3 according to the Dindo-Clavien scale (grade 1 to 5)
次要结局
- Intraoperative blood loss(Intraoperative (from entrance in the operating room to exit of the operating room))
- 7-day quality of recovery(One time point: 7 days after surgery (transplantation))
- Number of participants with a 7-day graft dysfunction(One time point: 7 days after surgery (transplantation))
- Number of participants with a 7-day acute kidney injury (AKI)(Over 7 days after surgery (criteria met at any day from surgery to day 7 after surgery))
- Number of participants who were transfused at least one unit of red blood cells (RBC) during the perioperative period of surgery(During surgery (from entrance in the operating to exit of the operating room) and up to 48 hours after surgery (from exit of the operating room to 48 hours after exit of the operating room))
- Number of participants who were transfused at least one unit of red blood cells (RBC) during surgery(Intraoperative (from entrance in the operating room to exit of the operating room))
- Number of participants who were transfused at least one unit of red blood cells (RBC) up to hospital discharge(From surgery to hospital discharge (from entrance in the operating room to hospital discharge) or 30 days, whichever comes first)
- Number of participants who were transfused at least one unit of any labile blood product up to hospital discharge(From surgery to hospital discharge (from entrance in the operating room to hospital discharge) or 30 days, whichever comes first)
- Number of participants with at least one postoperative hemorrhagic complication up to hospital discharge(Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first)
- Number of participants with postoperative acute kidney injury (AKI) up to hospital discharge(Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first)
- Number of participants requiring renal replacement therapy (RRT) up to hospital discharge(Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first)
- Number of participants with at least one postoperative graft complication up to hospital discharge(Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first)
- Number of participants with at least one postoperative infectious complication up to hospital discharge(Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first)
- Number of patients with a postoperative wound dehiscence up to hospital discharge(Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first)
- Number of patients with at least one postoperative pulmonary complication up to hospital discharge(Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first)
- Number of participants with at least one postoperative thromboembolic complication up to hospital discharge(Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first)
- Number of participants with a postoperative ICU readmission up to hospital discharge(From initial ICU discharge (planned postoperative ICU or step-down unit admission) to hospital discharge or 30 days, whichever comes first)
- Number of days not in an intensive care unit (ICU) at 30 days after surgery (30-day ICU-free days over 30 days)(From surgery to 30 days after surgery)
- Number of days without organ support at 30 days after surgery (30-day organ support free days)(From surgery to 30 days after surgery)
- Hospital length of stay(From surgery to hospital discharge (up to 12 months after surgery))
- Quality of life score(Two time points: 6 and 12 months after surgery)
- Rate of hospital readmissions(From hospital discharge after surgery to 12 months after surgery)
- Rate of 1-year graft complications(From surgery to 12 months after surgery)
- Rate of 1-year graft survival(From surgery to 12 months after surgery)
- Rate of 1-year recipient survival(From surgery to 12 months after surgery.)
- Costs of the intervention(Up to 12 months post-transplantation)