Overview
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.
Description
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.
Eligibility
Inclusion Criteria:
- Any adult patient ≥ 18 years of age undergoing liver transplantation for ESLD.
Exclusion Criteria:
- 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).
