Liver TransplantationREFIL-1NCT05647733
Restrictive Fluid Management In Liver Transplantation (REFIL) - Pilot
A study testing Low splanchnic blood volume restrictive fluid management strategy, Optimized cardiac output liberal fluid management strategy and Phlebotomy in people with Liver Transplantation and End-stage Liver Disease (ESLD), run by Centre hospitalier de l'Université de Montréal (CHUM) at 4 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Transplantation, End-stage Liver Disease (ESLD)
- What is being tested?
- Low splanchnic blood volume restrictive fluid management strategy, Optimized cardiac output liberal fluid management strategy and Phlebotomy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 138 participants
- Where
- 4 sitesCanada
- Study dates
- 25 Apr 2023to Feb 2027
- Phase
- Interventional
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
- Any adult patient ≥ 18 years of age undergoing liver transplantation for ESLD.
Who cannot join
- 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).
Trial locations and contacts
4 sites in 1 country.
Canada4 sites
London Health Sciences Centre
London, Ontario, N6G 2V4
Centre Hospitalier de l'Université de Montréal (CHUM)
Montreal, Quebec, H2X 0C1
McGill University Health Centre
Montreal, Quebec, H4A 3J1
Vancouver General Hospital
Vancouver, British Columbia, V5Z 1M9
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 Pilot Multicenter Randomized Controlled Trial (REFIL-1)
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.
Read more
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.
Read the detailed description
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).
- Being tested
- Low splanchnic blood volume restrictive fluid management strategy, Optimized cardiac output liberal fluid management strategy, Phlebotomy
- Keywords
- Hemodynamic management, Fluid management, Transfusions, Phlebotomy, Liver transplantation, 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 arm
Hemodynamic goal-directed restrictive fluid management strategy
Optimized cardiac output liberal fluid management strategyProcedure or surgery
Also called Liberal arm
Permissive hemodynamic goal-directed fluid management strategy that optimizes cardiac output throughout surgery
PhlebotomyProcedure or surgery
Retrieval of blood in a blood donation bag performed prior to dissection and transfused back after graft reperfusion
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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%. 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.
Recruitment rate
Overall recruitment rate ≥ 4 patients/month (across all sites)
Measured: 36 months (at study level)
Adherence
Protocol adherence > 90%, determined using a questionnaire
Measured: At time of surgery
Hospital outcome measurement completeness
A 30 days or hospital discharge outcome measurement > 90%
Measured: At 30 days (or hospital discharge) after surgery
6-month outcome measurement completeness
6-month outcome measurement > 90%
Measured: 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.
Measured: At time of surgery
Secondary outcomes (15)
Severe complications and graft lost
Composite incidence of severe complication (Dindo-Clavien III or more) or graft lost (retransplantation or death)
Measured: Up to 30 days or hospital discharge
Intraoperative blood loss
Intraoperative blood loss in mL
Measured: End of surgery
Intraoperative and perioperative blood product transfusions
Total number of transfused units of labile and non-labile blood products (red blood cells, plasma, platelets, cryoprecipitates, fibrinogen, prothrombin complex concentrates)
Measured: From randomization up to 30 days or hospital discharge, whichever comes first
7-day quality of recovery
7-day quality of recovery measured using the QoR-15 (Quality of Recovery) tool
Measured: 7 days after surgery
7-day graft dysfunction
7-day graft dysfunction (definition as reported by Olthoff et al.)
Measured: 7 days after surgery
7-day AKI (grade 2 or 3)
7-day AKI grade 2 or 3 using the KDIGO (Kidney Disease: Improving Global Outcomes) definition
Measured: 7 days after surgery
Any complication
Any of the following complications, graded according to the Dindo-Clavien classification system: hemorrhagic, graft related, pulmonary, infectious or thromboembolic.
Measured: From randomization up to 30 days or hospital discharge, whichever comes first
Any other severe complication
Any other severe complication (Dindo-Clavien III or more)
Measured: From randomization up to 30 days or hospital discharge, whichever comes first
Organ dysfunction and support
30-day organ support free days, using a recognized definition (as reported by Heyland et al.)
Measured: 30 days
Intensive care unit (ICU) length of stay
Total duration of stay (days) in the intensive care unit (ICU)
Measured: From randomization up to hospital discharge (ascertained up to end of follow-up at 1 year)
Hospital length of stay
Total duration of stay (days) in the hospital
Measured: From randomization up to hospital discharge (ascertained up to end of follow-up at 1 year)
Quality of life (QoL)
Quality of life (QoL) using the SF-36 tool
Measured: 6 & 12 months after surgery
Hospital readmissions
Hospital readmissions
Measured: From randomization up to 1 year after surgery
Graft complications
Graft complications
Measured: From randomization up to 1 year after surgery
Survival
Survival
Measured: From randomization up to 1 year after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2022
- Study start25 Apr 2023
- Primary completion24 Feb 2026
- Study completionFeb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver TransplantationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 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.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 138 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre hospitalier de l'Université de Montréal (CHUM)
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Canadian Donation and Transplantation Research Program (CDTRP), Canadian Perioperative Anesthesia Clinical Trial (PACT) Group
- Responsible party
- Sponsor
- Investigators
- Francois Martin Carrier, MD, Principal investigator, Centre hospitalier université de Montréal
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05647733
- Sponsor's protocol ID
- 2023-11173
- Other IDs
- 2023
- Acronym
- REFIL-1
- Status last verified
- Jun 2026
- First submitted
- 30 Nov 2022
- Last updated
- 16 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: End-of-grant KT modalities will be used to reach other important stakeholders, researchers and members of the anesthesia and transplantation community: scientific meetings, publication in an open-access journal, and public presentations with patient partners. Knowledge diffusion on potential difficulties of conducting such trials (and solutions) will be transferred to the research community through the Canadian Perioperative Anesthesia Clinical Trial group (PACT), the Canadian Donation and Transplantation Research Program (CDTRP) and the International Liver Transplantation Society (ILTS) meetings.