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
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
72
Hemodynamic goal-directed restrictive fluid management strategy.
Permissive intraoperative hemodynamic goal-directed fluid management strategy that optimizes cardiac output throughout surgery
Retrieval of blood in a blood donation bag performed prior to dissection and transfused back after graft reperfusion
London Health Sciences Centre
London, Ontario, Canada
RECRUITINGCentre Hospitalier de l'Université de Montréal (CHUM)
Montreal, Quebec, Canada
RECRUITINGMcGill University Health Centre
Montreal, Quebec, Canada
RECRUITINGRecruitment rate
Overall recruitment rate ≥ 4 patients/month (across all sites)
Time frame: 18 months (at study level)
Adherence
Protocol adherence \> 90%, defined using a questionnaire
Time frame: At time of surgery
Hospital outcome measurement completeness
A 30 days or hospital discharge outcome measurement \> 90%
Time frame: At 30 days (or hospital discharge) after surgery
6-month outcome measurement completeness
6-month outcome measurement \> 90%
Time frame: 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.
Time frame: At time of surgery
Severe complications and graft lost
Composite incidence of severe complication (Dindo-Clavien III or more) or graft lost (retransplantation or death)
Time frame: Up to 30 days or hospital discharge
Intraoperative blood loss
Intraoperative blood loss in mL
Time frame: 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)
Time frame: 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
Time frame: 7 days after surgery
7-day graft dysfunction
7-day graft dysfunction (definition as reported by Olthoff et al.)
Time frame: 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
Time frame: 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.
Time frame: 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)
Time frame: 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.)
Time frame: 30 days
Intensive care unit (ICU) length of stay
Total duration of stay (days) in the intensive care unit (ICU)
Time frame: 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
Time frame: 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
Time frame: 6 & 12 months after surgery
Hospital readmissions
Hospital readmissions
Time frame: From randomization up to 1 year after surgery
Graft complications
Graft complications
Time frame: From randomization up to 1 year after surgery
Survival
Survival
Time frame: From randomization up to 1 year after surgery
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