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)
| Registry | NCT05647733, acronym REFIL-1 |
|---|---|
| Status | Active not recruiting |
| Phase | Not applicable |
| Study type | Interventional; randomized, parallel, masking: triple, treatment |
| Enrollment | 138 (Estimated) |
| Sponsor | Centre hospitalier de l'Université de Montréal (CHUM) (Other); collaborators: Canadian Institutes of Health Research (CIHR), Canadian Donation and Transplantation Research Program (CDTRP), Canadian Perioperative Anesthesia Clinical Trial (PACT) Group |
| Conditions | Liver Transplantation, End-stage Liver Disease (ESLD) |
| Interventions | Low splanchnic blood volume restrictive fluid management strategy, Optimized cardiac output liberal fluid management strategy, Phlebotomy (Procedure) |
| Dates | start 2023-04-25, primary completion 2026-02-24, completion 2027-02-01 (estimated), first posted 2022-12-12, last updated 2026-06-16 |
| Locations | 4 sites in Canada |
Related Papers Related Patents Related Grants Related Experts
All trials for Liver Transplantation All trials for End-stage Liver Disease (ESLD) All trials of Low splanchnic blood volume restrictive fluid management strategy All trials of Optimized cardiac output liberal fluid management strategy
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.
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).
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Restrictive group - Low splanchnic blood volume Restrictive fluid management strategy | Experimental | Procedure: Low splanchnic blood volume restrictive fluid management strategy; Procedure: Phlebotomy | 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. |
| Liberal group - Optimized cardiac output liberal fluid management strategy | Active comparator | Procedure: 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%. |
Sex: All, ages: 18 Years to any
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).
| Facility | City | Country | Status |
|---|---|---|---|
| Vancouver General Hospital | Vancouver, British Columbia | Canada | |
| London Health Sciences Centre | London, Ontario | Canada | |
| Centre Hospitalier de l'Université de Montréal (CHUM) | Montreal, Quebec | Canada | |
| McGill University Health Centre | Montreal, Quebec | Canada |
NIH grants: 2023