Restrictive Fluid Management In Liver Transplantation (REFIL)

Centre hospitalier de l'Université de Montréal (CHUM)

Status: Enrolling

Conditions: Liver Transplantation

Treatments: Procedure: Optimized cardiac output liberal fluid management strategy; Procedure: Low splanchnic blood volume restrictive fluid management strategy; Procedure: Phlebotomy

Study type: Interventional

Funder types: Other

Identifiers

NCT05647733

2023-11173

Details and patient eligibility

About

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.

Full 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.

Enrollment: 138 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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138 participants in 2 patient groups

Restrictive group - Low splanchnic blood volume Restrictive fluid management strategy

Experimental group

Description:

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.

Treatment:

Procedure: Phlebotomy

Procedure: Low splanchnic blood volume restrictive fluid management strategy

Liberal group - Optimized cardiac output liberal fluid management strategy

Active Comparator group

Description:

This strategy involves administering 250 ml fluid boluses until SV stops increasing by more than 10% or until PPV is below 12%.

Treatment:

Procedure: Optimized cardiac output liberal fluid management strategy