Restrictive Fluid Management In Liver Transplantation (REFIL)

NCT07695363 | Recruiting DMC

• 1 other identifier: 22.206
• Study Type: interventional
• Target: 866
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Liver Transplantation (LT); End-stage Liver Disease (ESLD)

Keywords

Liver Transplantation; Phlebotomy; Hemodynamic Management; Fluid Management; Transfusions; Liver Diseases

Outcome Measures

Primary Outcomes (1)

• Number of participants with at least one severe complication

  Incidence of at least one severe complications defined as a complication of grade ≥ 3 according to the Dindo-Clavien scale (grade 1 to 5)

  Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first

Secondary Outcomes (26)

• 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)

• 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)

Study Arms (2)

Restrictive group - Low splanchnic blood volume restrictive fluid management strategy

EXPERIMENTAL

A phlebotomy (a procedure where the patient's blood is drawn, similar to a blood donation, without fluid replacement) at the start of the surgery combined with fluid restriction (use of vasopressor preferentially to treat hemodynamic instability with tolerance to relative hypovolemia defined as a Pulse Pressure Variation (PPV) or Stroke Volume (SVV) up to 18%). Fluids will be administered to compensate for blood loss and/or treat severe hemodynamic instability. Blood collected by phlebotomy will always be transfused back at the beginning of the reperfusion phase, during which fluid management will be based on goal-directed therapy (GDT) using either PPV or SV, as in the control group.

Procedure: Low splanchnic blood volume restrictive fluid management strategy; Procedure: Phlebotomy

Liberal group - Optimized cardiac output liberal fluid management strategy

ACTIVE COMPARATOR

Goal-directed therapy (GDT): Patients will receive 250 ml fluid boluses until SV stops increasing by more than 10% or until PPV is below 12%. Fluids will thus be used preferentially to treat hemodynamic instability. Fluids will also be administered to compensate for blood loss and/or treat severe hemodynamic instability.

Procedure: Optimized cardiac output liberal fluid management strategy

Interventions

Low splanchnic blood volume restrictive fluid management strategy PROCEDURE

Hemodynamic goal-directed restrictive fluid management strategy

Also known as: Restrictive

Restrictive group - Low splanchnic blood volume restrictive fluid management strategy

Phlebotomy PROCEDURE

Blood drawn in a blood donation bag prior to dissection and transfused back after graft reperfusion

Restrictive group - Low splanchnic blood volume restrictive fluid management strategy

Optimized cardiac output liberal fluid management strategy PROCEDURE

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

Also known as: Liberal

Liberal group - Optimized cardiac output liberal fluid management strategy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult ≥ 18 years old
• Undergoing liver transplantation (LT)
• End-stage liver disease (ESLD) (with or without hepatocellular carcinoma) as the indication for transplantation.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre hospitalier de l'Université de Montréal (CHUM): lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Canadian Perioperative Anesthesia Clinical Trial (PACT) Group: collaborator
• Canadian Donation and Transplantation Research Program (CDTRP): collaborator

Study Sites (4)

Vancouver General Hospital (VGH)

Vancouver, British Columbia, V5Z 1M9, Canada

RECRUITING

London Health Sciences Centre (LHSC)

London, Ontario, N6G 2V4, Canada

RECRUITING

Centre hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, H2X 0C1, Canada

RECRUITING

McGill University Health Centre (MUHC)

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

Related Publications (4)

• Carrier FM, Chasse M, Wang HT, Aslanian P, Iorio S, Bilodeau M, Turgeon AF. Restrictive fluid management strategies and outcomes in liver transplantation: a systematic review. Can J Anaesth. 2020 Jan;67(1):109-127. doi: 10.1007/s12630-019-01480-y. Epub 2019 Sep 25.

  PMID: 31556006 BACKGROUND

• Thacker JK, Mountford WK, Ernst FR, Krukas MR, Mythen MM. Perioperative Fluid Utilization Variability and Association With Outcomes: Considerations for Enhanced Recovery Efforts in Sample US Surgical Populations. Ann Surg. 2016 Mar;263(3):502-10. doi: 10.1097/SLA.0000000000001402.

  PMID: 26565138 BACKGROUND

• Shin CH, Long DR, McLean D, Grabitz SD, Ladha K, Timm FP, Thevathasan T, Pieretti A, Ferrone C, Hoeft A, Scheeren TWL, Thompson BT, Kurth T, Eikermann M. Effects of Intraoperative Fluid Management on Postoperative Outcomes: A Hospital Registry Study. Ann Surg. 2018 Jun;267(6):1084-1092. doi: 10.1097/SLA.0000000000002220.

  PMID: 28288059 BACKGROUND

• Parikh A, Washburn KW, Matsuoka L, Pandit U, Kim JE, Almeda J, Mora-Esteves C, Halff G, Genyk Y, Holland B, Wilson DJ, Sher L, Koneru B. A multicenter study of 30 days complications after deceased donor liver transplantation in the model for end-stage liver disease score era. Liver Transpl. 2015 Sep;21(9):1160-8. doi: 10.1002/lt.24181.

  PMID: 25991395 BACKGROUND

Related Links

• Website

MeSH Terms

Conditions

End Stage Liver Disease; Liver Diseases

Interventions

Phlebotomy

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Blood Specimen Collection; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• François Martin Carrier, MD

  Centre hospitalier de l'Université de Montréal (CHUM)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Manuela Mbacfou, MSc

CONTACT

514-890-8000; manuela.mbacfou.temgoua.chum@ssss.gouv.qc.ca

François Martin Carrier, MD

CONTACT

514-890-8000; francois.martin.carrier.med@ssss.gouv.qc.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are allocated to either group in a 1:1 ratio. Participants are only randomized once a viable graft is available.

Study Record Dates

• First Submitted: June 15, 2026
• First Posted: July 10, 2026
• Study Start: February 15, 2026
• Primary Completion (Estimated): November 1, 2030
• Study Completion (Estimated): November 1, 2031
• Last Updated: July 10, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4)