Restrictive Fluid Management In Liver Transplantation (REFIL)

NCT05647733 | Recruiting DMC

• 1 other identifier: 2023-11173
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Liver Transplantation

Keywords

Hemodynamic management; Fluid management; Transfusions; Phlebotomy; Liver transplantation

Outcome Measures

Primary Outcomes (5)

• Recruitment rate

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

  36 months (at study level)

• Adherence

  Protocol adherence \> 90%, determined using a questionnaire

  At time of surgery

• Hospital outcome measurement completeness

  A 30 days or hospital discharge outcome measurement \> 90%

  At 30 days (or hospital discharge) after surgery

• 6-month outcome measurement completeness

  6-month outcome measurement \> 90%

  6 months after surgery

• Mean difference in total volume received

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

  At time of surgery

Secondary Outcomes (15)

• Severe complications and graft lost

  Up to 30 days or hospital discharge

• Intraoperative blood loss

  End of surgery

• Intraoperative and perioperative blood product transfusions

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

• 7-day quality of recovery

  7 days after surgery

• 7-day graft dysfunction

  7 days after surgery

Study Arms (2)

Restrictive group - Low splanchnic blood volume Restrictive fluid management strategy

EXPERIMENTAL

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.

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

Liberal group - Optimized cardiac output liberal fluid management strategy

ACTIVE COMPARATOR

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

Procedure: Optimized cardiac output liberal fluid management strategy

Interventions

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 arm

Liberal group - Optimized cardiac output liberal fluid management strategy

Phlebotomy PROCEDURE

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

Restrictive group - Low splanchnic blood volume Restrictive fluid management strategy

Low splanchnic blood volume restrictive fluid management strategy PROCEDURE

Hemodynamic goal-directed restrictive fluid management strategy

Also known as: Restrictive arm

Restrictive group - Low splanchnic blood volume Restrictive fluid management strategy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Any adult patient ≥ 18 years of age undergoing liver transplantation for ESLD.

You may not qualify if:

• 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).

Sponsors & Collaborators

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

Study Sites (4)

Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

RECRUITING

London Health Sciences Centre

London, Ontario, N6G 2V4, Canada

RECRUITING

Centre Hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, H2X 0C1, Canada

RECRUITING

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

MeSH Terms

Interventions

Phlebotomy

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

• Francois Martin Carrier, MD

  Centre hospitalier université de Montréal

  PRINCIPAL INVESTIGATOR

Central Study Contacts

François Martin Carrier, MD

CONTACT

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

Manuela Mbacfou, MSc

CONTACT

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Only the anesthesiology team will know the allocation received, as they must implement the intervention, thereby limiting differential outcome classification bias because they will not assess outcomes. Patients, surgeons, and non-anesthesia health professionals will be blinded to the allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be allocated to either group in a 1:1 ratio. A research assistant will randomize the patient once a viable graft is confirmed, and then share the allocation with the anesthesiology team.

Study Record Dates

• First Submitted: November 30, 2022
• First Posted: December 12, 2022
• Study Start: April 25, 2023
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4)