Skip to main content
OpenTrials
Active, Not Recruiting

NCT Number: NCT05647733

Restrictive Fluid Management In Liver Transplantation (REFIL) - Pilot

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Liver Transplantation Digestive System Diseases End Stage Liver Disease End-stage Liver Disease (ESLD) Hepatic Insufficiency Liver Diseases Liver Failure

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Vancouver General Hospital, Vancouver, British Columbia, Canada

Loading trial locations.

About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

Low splanchnic blood volume restrictive fluid management strategy

Procedure

Hemodynamic goal-directed restrictive fluid management strategy

Other names: Restrictive arm

Optimized cardiac output liberal fluid management strategy

Procedure

Permissive hemodynamic goal-directed fluid management strategy that optimizes cardiac output throughout surgery

Other names: Liberal arm

Phlebotomy

Procedure

Retrieval of blood in a blood donation bag performed prior to dissection and transfused back after graft reperfusion

Primary outcomes

  1. Recruitment rate

    Time frame: 36 months (at study level)

    Overall recruitment rate ≥ 4 patients/month (across all sites)

  2. Adherence

    Time frame: At time of surgery

    Protocol adherence > 90%, determined using a questionnaire

  3. Hospital outcome measurement completeness

    Time frame: At 30 days (or hospital discharge) after surgery

    A 30 days or hospital discharge outcome measurement > 90%

  4. 6-month outcome measurement completeness

    Time frame: 6 months after surgery

    6-month outcome measurement > 90%

  5. Mean difference in total volume received

    Time frame: At time of surgery

    A mean difference in total volume received (crystalloids and colloids combined) > 1000 ml between groups.

Secondary outcomes

  1. Severe complications and graft lost

    Time frame: Up to 30 days or hospital discharge

    Composite incidence of severe complication (Dindo-Clavien III or more) or graft lost (retransplantation or death)

  2. Intraoperative blood loss

    Time frame: End of surgery

    Intraoperative blood loss in mL

  3. Intraoperative and perioperative blood product transfusions

    Time frame: From randomization up to 30 days or hospital discharge, whichever comes first

    Total number of transfused units of labile and non-labile blood products (red blood cells, plasma, platelets, cryoprecipitates, fibrinogen, prothrombin complex concentrates)

  4. 7-day quality of recovery

    Time frame: 7 days after surgery

    7-day quality of recovery measured using the QoR-15 (Quality of Recovery) tool

  5. 7-day graft dysfunction

    Time frame: 7 days after surgery

    7-day graft dysfunction (definition as reported by Olthoff et al.)

  6. 7-day AKI (grade 2 or 3)

    Time frame: 7 days after surgery

    7-day AKI grade 2 or 3 using the KDIGO (Kidney Disease: Improving Global Outcomes) definition

  7. Any complication

    Time frame: From randomization up to 30 days or hospital discharge, whichever comes first

    Any of the following complications, graded according to the Dindo-Clavien classification system: hemorrhagic, graft related, pulmonary, infectious or thromboembolic.

  8. Any other severe complication

    Time frame: From randomization up to 30 days or hospital discharge, whichever comes first

    Any other severe complication (Dindo-Clavien III or more)

  9. Organ dysfunction and support

    Time frame: 30 days

    30-day organ support free days, using a recognized definition (as reported by Heyland et al.)

  10. Intensive care unit (ICU) length of stay

    Time frame: From randomization up to hospital discharge (ascertained up to end of follow-up at 1 year)

    Total duration of stay (days) in the intensive care unit (ICU)

  11. Hospital length of stay

    Time frame: From randomization up to hospital discharge (ascertained up to end of follow-up at 1 year)

    Total duration of stay (days) in the hospital

  12. Quality of life (QoL)

    Time frame: 6 & 12 months after surgery

    Quality of life (QoL) using the SF-36 tool

  13. Hospital readmissions

    Time frame: From randomization up to 1 year after surgery

    Hospital readmissions

  14. Graft complications

    Time frame: From randomization up to 1 year after surgery

    Graft complications

  15. Survival

    Time frame: From randomization up to 1 year after surgery

    Survival

Sponsors and collaborators

Lead sponsor

Centre hospitalier de l'Université de Montréal (CHUM)

Other

Collaborators

  • Canadian Donation and Transplantation Research Program (CDTRP)
  • Canadian Institutes of Health Research (CIHR)
  • Canadian Perioperative Anesthesia Clinical Trial (PACT) Group

Registry information

Official study title

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)

Acronym: REFIL-1

Important dates

Study start
2023
Primary completion
2026
Study completion
2027
First posted
Dec 12, 2022
Registry last updated
Jun 16, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.