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Liver Transplantation (LT)REFIL-2NCT07695363

Restrictive Fluid Management In Liver Transplantation (REFIL)

A study testing Low splanchnic blood volume restrictive fluid management strategy, Phlebotomy and Optimized cardiac output liberal fluid management strategy in people with Liver Transplantation (LT) and End-stage Liver Disease (ESLD), run by Centre hospitalier de l'Université de Montréal (CHUM) at 4 sites in Canada.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Low splanchnic blood volume restrictive fluid management strategy, Phlebotomy and Optimized cardiac output liberal fluid management strategy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
866 participants
Where
4 sitesCanada
Study dates
15 Feb 2026to Nov 2031
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • 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.

Trial locations and contacts

4 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Manuela Mbacfou, MSc contact

514-890-8000 ext. 31576

manuela.mbacfou.temgoua.chum@ssss.gouv.qc.ca

François Martin Carrier, MD contact

514-890-8000

francois.martin.carrier.med@ssss.gouv.qc.ca

Canada4 sites, 4 recruiting

  • London Health Sciences Centre (LHSC)

    London, Ontario, N6G 2V4

    Nelson Javier Gonzalez Valencia, MD, 519-661-2111, nelson.gonzalezvalencia@lhsc.on.ca

    Nelson Javier Gonzalez Valencia, MD

    Recruiting

  • Centre hospitalier de l'Université de Montréal (CHUM)

    Montreal, Quebec, H2X 0C1

    Manuela Mbacfou, MSc, 514-890-8000 ext. 31576, manuela.mbacfou.temgoua.chum@ssss.gouv.qc.ca

    François Martin Carrier, MD

    Recruiting

  • McGill University Health Centre (MUHC)

    Montreal, Quebec, H4A 3J1

    Stanislas Kandelman, MD, 514-934-1934, stanislas.kandelman.med@ssss.gouv.qc.ca

    Stanislas Kandelman, MD

    Recruiting

  • Vancouver General Hospital (VGH)

    Vancouver, British Columbia, V5Z 1M9

    JeiEung Park, MD, 604-875-4111, jeieung.park@vch.ca

    JeiEung Park, MD

    Recruiting

Other trials in Canada

About this study

Official 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 Multicenter Randomized Controlled Trial (REFIL-2)

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.

Read the detailed description

People with advanced liver disease have poor blood circulation, and too much blood accumulates in the abdomen (a condition known as high intra-abdominal blood volume). However, liver transplantation (LT) is a complex surgery during which the patient can lose a significant amount of blood and blood pressure can fluctuate widely. Therefore, restricting fluids and using medications to raise blood pressure is a strategy that could reduce blood loss and potentially also certain complications after surgery. Furthermore, phlebotomy appears to reduce intra-abdominal blood volume, blood loss, drops in blood pressure, and the need for red blood cell transfusions, potentially improving recovery after surgery. This study therefore aims to determine the best way to manage fluids during a liver transplantation by comparing these two care strategies. Another goal of the study is to measure the cost-effectiveness of the proposed intervention.

Hypothesis: An intraoperative low splanchnic blood volume restrictive fluid management strategy is superior to an optimized cardiac-output liberal fluid management strategy in reducing postoperative severe complications after liver transplantation

Design: Multicenter blinded parallel arm randomized controlled trial

Study population: Adult patients undergoing a liver transplantation for end-stage liver disease (ESLD)

All participants will be followed during their index hospitalization up to post-transplantation Day 30 (whichever comes first), and for 12 months post-transplantation to assess some clinical outcomes, quality of life (QoL), and survival (being alive beyond the index hospitalization).

Participation in this study lasts 12 months.

The results of this study will help determine whether or not to recommend a low splanchnic blood volume restrictive fluid management strategy for people who undergo a liver transplantation.

This study is conducted in two phases: a pilot phase, which demonstrated feasibility across Canada, followed by the current larger-scale phase (REFIL-2).

Being tested
Low splanchnic blood volume restrictive fluid management strategy, Phlebotomy, Optimized cardiac output liberal fluid management strategy
Keywords
Liver Transplantation, Phlebotomy, Hemodynamic Management, Fluid Management, Transfusions, Liver Diseases
Medical subject headings
End Stage Liver Disease, Liver Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Low splanchnic blood volume restrictive fluid management strategyProcedure or surgery

    Also called Restrictive

    Hemodynamic goal-directed restrictive fluid management strategy

  • PhlebotomyProcedure or surgery

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

  • Optimized cardiac output liberal fluid management strategyProcedure or surgery

    Also called Liberal

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

Study groups in NCT07695363
Study groupRoleWhat they receive
Restrictive group - Low splanchnic blood volume restrictive fluid management strategyExperimentalA 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.
Receives: Procedure: Low splanchnic blood volume restrictive fluid management strategy; Procedure: Phlebotomy
Liberal group - Optimized cardiac output liberal fluid management strategyActive comparatorGoal-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.
Receives: Procedure: Optimized cardiac output liberal fluid management strategy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

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

Secondary outcomes (26)

  1. Number of participants who were transfused at least one unit of red blood cells (RBC) during the perioperative period of surgery

    Incidence of participants transfused at least 1 unit of RBC during the perioperative period of surgery

    Measured: 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)

  2. Number of participants who were transfused at least one unit of red blood cells (RBC) during surgery

    Incidence of at least one RBC transfusion during surgery

    Measured: Intraoperative (from entrance in the operating room to exit of the operating room)

  3. Intraoperative blood loss

    Blood loss as estimated by clinicians

    Measured: Intraoperative (from entrance in the operating room to exit of the operating room)

  4. 7-day quality of recovery

    Quality of recovery measured using the 15-item Quality of Recovery (QoR-15) score. Each item is scored on an 11-point numerical rating scale (0-10) for a total between 0 and 150, 0 being the worst possible recovery and 150 being a perfect recovery.

    Measured: One time point: 7 days after surgery (transplantation)

  5. Number of participants with a 7-day graft dysfunction

    Incidence of graft dysfunction (as per Olthoff's definition)

    Measured: One time point: 7 days after surgery (transplantation)

  6. Number of participants with a 7-day acute kidney injury (AKI)

    Acute kidney injury (AKI) of KDIGO grade 2 or 3

    Measured: Over 7 days after surgery (criteria met at any day from surgery to day 7 after surgery)

  7. Number of participants who were transfused at least one unit of red blood cells (RBC) up to hospital discharge

    Incidence of at least one RBC transfusion from surgery to hospital discharge

    Measured: From surgery to hospital discharge (from entrance in the operating room to hospital discharge) or 30 days, whichever comes first

  8. Number of participants who were transfused at least one unit of any labile blood product up to hospital discharge

    Incidence of at least one labile blood product transfused from surgery up to hospital discharge

    Measured: From surgery to hospital discharge (from entrance in the operating room to hospital discharge) or 30 days, whichever comes first

  9. Number of participants with at least one postoperative hemorrhagic complication up to hospital discharge

    Incidence of at least one postoperative hemorrhagic complication, defined as any bleeding episode associated with a drop of hemoglobin of 20 g/L within 24 hours of bleeding, requiring 2 blood units within 24 hours of bleeding, a surgical hemostasis or an angioembolization.

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

  10. Number of participants with postoperative acute kidney injury (AKI) up to hospital discharge

    Incidence of any postoperative acute kidney injury (AKI) (any grade as per KDIGO criteria) up to hospital discharge

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

  11. Number of participants requiring renal replacement therapy (RRT) up to hospital discharge

    Incidence of postoperative requirement for renal replacement therapy (RRT) [hemodialysis or hemofiltration] up to hospital discharge

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

  12. Number of participants with at least one postoperative graft complication up to hospital discharge

    Incidence of at least one postoperative graft complication (primary non-function, vascular, biliary) or retransplantation up to hospital discharge

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

  13. Number of participants with at least one postoperative infectious complication up to hospital discharge

    Incidence of any postoperative infectious complication (other than pneumonia) up to hospital discharge

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

  14. Number of patients with a postoperative wound dehiscence up to hospital discharge

    Incidence of postoperative wound dehiscence or evisceration up to hospital discharge

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

  15. Number of patients with at least one postoperative pulmonary complication up to hospital discharge

    Incidence of any postoperative pulmonary complications (atelectasis, pneumonia, pulmonary oedema) up to hospital discharge

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

  16. Number of participants with at least one postoperative thromboembolic complication up to hospital discharge

    Incidence of at least one thromboembolic complication (deep vein thrombosis, pulmonary embolism, myocardial infraction, stroke, mesenteric ischemia) up to hospital discharge

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

  17. Number of participants with a postoperative ICU readmission up to hospital discharge

    Incidence of ICU readmissions after initial discharge (from the planned postoperative ICU or step-down unit admission) to hospital discharge

    Measured: From initial ICU discharge (planned postoperative ICU or step-down unit admission) to hospital discharge or 30 days, whichever comes first

  18. Number of days not in an intensive care unit (ICU) at 30 days after surgery (30-day ICU-free days over 30 days)

    Number of days alive and not hospitalized in an ICU.

    0 means 30 consecutive days in the ICU or death within 30 days without any day without being in an ICU from surgery to death.

    30 means no days hospitalized in an ICU from surgery to the 30-day time point.

    Measured: From surgery to 30 days after surgery

  19. Number of days without organ support at 30 days after surgery (30-day organ support free days)

    Number of days alive without renal replacement therapy, mechanical ventilation or vasopressor 30 days after surgery.

    0 means 30 consecutive days with any organ support or death within 30 days without any day without organ support from surgery to death.

    30 means no days with organ support from surgery to the 30-day time point.

    Measured: From surgery to 30 days after surgery

  20. Hospital length of stay

    Length of hospital stay (days)

    Measured: From surgery to hospital discharge (up to 12 months after surgery)

  21. Quality of life score

    Quality of life (QoL) score using the 36-item Short Form health survey questionnaire (SF-36). Score ranges from 0 (worst possible health) to 100 (best possible health).

    Measured: Two time points: 6 and 12 months after surgery

  22. Rate of hospital readmissions

    Number of postoperative hospital readmissions over 12 months after surgery

    Measured: From hospital discharge after surgery to 12 months after surgery

  23. Rate of 1-year graft complications

    Time to any graft complication (vascular or biliary) to 1 year after surgery

    Measured: From surgery to 12 months after surgery

  24. Rate of 1-year graft survival

    Time to graft lost (death of retransplantation) up to 1 year after surgery.

    Censoring will occur if lost to follow-up or 1 year after surgery.

    Measured: From surgery to 12 months after surgery

  25. Rate of 1-year recipient survival

    Time to death up to 1 year after surgery.

    Censoring will occur if lost to follow-up or at 12 months after surgery.

    Measured: From surgery to 12 months after surgery.

  26. Costs of the intervention

    Complication-related costs (total and subcomponent costs including complications, ressource utilization and hospital readmissions)

    Measured: Up to 12 months post-transplantation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jul 2026
  2. Study start15 Feb 2026
  3. Primary completionNov 2030 (estimated)
  4. Study completionNov 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Participants are allocated to either group in a 1:1 ratio. Participants are only randomized once a viable graft is available.
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
866 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07695363
Sponsor's protocol ID
22.206
Acronym
REFIL-2
Status last verified
Jun 2026
First submitted
15 Jun 2026
Last updated
10 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: End-of-study knowledge translation (KT) planned

Publications

  • 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.

    PubMed 31556006

  • 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.

    PubMed 26565138

  • 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.

    PubMed 28288059

  • 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.

    PubMed 25991395

Questions about this trial

What is this clinical trial studying?

A study testing Low splanchnic blood volume restrictive fluid management strategy, Phlebotomy and Optimized cardiac output liberal fluid management strategy in people with Liver Transplantation (LT) and End-stage Liver Disease (ESLD), run by Centre hospitalier de l'Université de Montréal (CHUM) at 4 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 10 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Manuela Mbacfou, MSc (514-890-8000 ext. 31576, manuela.mbacfou.temgoua.chum@ssss.gouv.qc.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with at least one severe complication (time frame: Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07695363, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2026.

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