Clinical trial NCT05647733: Restrictive Fluid Management In Liver Transplantation (REFIL)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Liver Transplantation
Keywords: Hemodynamic management
Fluid management
Transfusions
Phlebotomy
Lead sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Canadian Donation and Transplantation Research Program (CDTRP)
name: Canadian Perioperative Anesthesia Clinical Trial (PACT) Group
First posted: 2022-12-12
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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 allocation with the anesthesiology team.
Primary purpose: TREATMENT

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 undergoing a liver transplantation not meeting any exclusion criteria.

Primary endpoint: The primary feasibility endpoint is an overall recruitment rate ≥ 4 patients/month across all three participating sites.

Secondary endpoint: The secondary feasibility endpoints are 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

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 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 a multicentre internal pilot parallel arm randomized trial comparing two intraoperative hemodynamic and splanchnic blood volume management strategies in LT recipients.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* 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).

Primary outcomes:
measure: Recruitment rate
timeFrame: 18 months (at study level)
measure: Adherence
timeFrame: At time of surgery
measure: Hospital outcome measurement completeness
timeFrame: At 30 days (or hospital discharge) after surgery
measure: 6-month outcome measurement completeness
timeFrame: 6 months after surgery
measure: Mean difference in total volume received
timeFrame: At time of surgery
Secondary outcomes:
measure: Severe complications and graft lost
timeFrame: Up to 30 days or hospital discharge
measure: Intraoperative blood loss
timeFrame: End of surgery
measure: Intraoperative and perioperative blood product transfusions
timeFrame: From randomization up to 30 days or hospital discharge, whichever comes first
measure: 7-day quality of recovery
timeFrame: 7 days after surgery
measure: 7-day graft dysfunction
timeFrame: 7 days after surgery
measure: 7-day AKI (grade 2 or 3)
timeFrame: 7 days after surgery
measure: Any complication
timeFrame: From randomization up to 30 days or hospital discharge, whichever comes first
measure: Any other severe complication
timeFrame: From randomization up to 30 days or hospital discharge, whichever comes first
measure: Organ dysfunction and support
timeFrame: 30 days
measure: Intensive care unit (ICU) length of stay
timeFrame: From randomization up to hospital discharge (ascertained up to end of follow-up at 1 year)
measure: Hospital length of stay
timeFrame: From randomization up to hospital discharge (ascertained up to end of follow-up at 1 year)
measure: Quality of life (QoL)
timeFrame: 6 & 12 months after surgery
measure: Hospital readmissions
timeFrame: From randomization up to 1 year after surgery
measure: Graft complications
timeFrame: From randomization up to 1 year after surgery
measure: Survival
timeFrame: From randomization up to 1 year after surgery
Other outcomes:
Locations:
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal (CHUM)
state: Quebec
city: Montréal
country: Canada
facility: McGill University Health Centre
state: Quebec
Study officials:
affiliation: Centre hospitalier université de Montréal
name: Francois-Martin Carrier, MD
role: PRINCIPAL_INVESTIGATOR
References: