Recruiting

Low Splanchnic Volume vs. Optimized Cardiac-Output

Sponsor:

Centre hospitalier de l'Université de Montréal (CHUM)

Code:

NCT07695363

Conditions

Liver Transplantation (LT)

End-stage Liver Disease (ESLD)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Low splanchnic blood volume restrictive fluid management strategy

Phlebotomy

Optimized cardiac output liberal fluid management strategy

Study Details

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)

Study ID

NCT07695363

Start date

Feb 15, 2026

Status verified date

Jun, 2026

Completion date

Nov, 2031

Anticipated

Primary completion date

Nov, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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

Exclusion Criteria:

1. 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)
2. Undergoing combined solid organ transplantations
3. 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)
4. Physician refusal to enroll the patient.

Study Design

Enrollment

866 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Restrictive group - Low splanchnic blood volume restrictive fluid management strategy

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.

active comparator: Liberal group - Optimized cardiac output liberal fluid management strategy

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.

Interventions

Low splanchnic blood volume restrictive fluid management strategy

Hemodynamic goal-directed restrictive fluid management strategy

Phlebotomy

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

Optimized cardiac output liberal fluid management strategy

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

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 ]

Central Contacts and Locations

Central contacts

Manuela Mbacfou, MSc

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

François Martin Carrier, MD

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

Locations

Vancouver General Hospital (VGH)

Recruiting

Vancouver, British Columbia, Canada, V5Z 1M9

Contacts

JeiEung Park, MD

604-875-4111jeieung.park@vch.ca

Principal Investigator:

JeiEung Park, MD

London Health Sciences Centre (LHSC)

Recruiting

London, Ontario, Canada, N6G 2V4

Contacts

Nelson Javier Gonzalez Valencia, MD

519-661-2111nelson.gonzalezvalencia@lhsc.on.ca

Principal Investigator:

Nelson Javier Gonzalez Valencia, MD

Centre hospitalier de l'Université de Montréal (CHUM)

Recruiting

Montreal, Quebec, Canada, H2X 0C1

Contacts

Manuela Mbacfou, MSc

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

Principal Investigator:

François Martin Carrier, MD

McGill University Health Centre (MUHC)

Recruiting

Montreal, Quebec, Canada, H4A 3J1

Contacts

Stanislas Kandelman, MD

514-934-1934stanislas.kandelman.med@ssss.gouv.qc.ca

Principal Investigator:

Stanislas Kandelman, MD

More Information

Sponsor

Centre hospitalier de l'Université de Montréal (CHUM)

Last update posted

Jul 10, 2026

Last verified

Jun, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Centre hospitalier de l'Université de Montréal (CHUM) on 2026-07-10.