End-stage Liver Disease (ESLD), Liver Transplantation
Conditions
Keywords
Hemodynamic management, Fluid management, Transfusions, Phlebotomy, Liver transplantation, Liver Diseases
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.
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).
Interventions
Hemodynamic goal-directed restrictive fluid management strategy
Permissive hemodynamic goal-directed fluid management strategy that optimizes cardiac output throughout surgery
PROCEDUREPhlebotomy
Retrieval of blood in a blood donation bag performed prior to dissection and transfused back after graft reperfusion
Sponsors
Centre hospitalier de l'Université de Montréal (CHUM)
Canadian Institutes of Health Research (CIHR)
Canadian Donation and Transplantation Research Program (CDTRP)
Canadian Perioperative Anesthesia Clinical Trial (PACT) Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
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.
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 the allocation with the anesthesiology team.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recruitment rate | 36 months (at study level) | Overall recruitment rate ≥ 4 patients/month (across all sites) |
| Adherence | At time of surgery | Protocol adherence \> 90%, determined using a questionnaire |
| Hospital outcome measurement completeness | At 30 days (or hospital discharge) after surgery | A 30 days or hospital discharge outcome measurement \> 90% |
| 6-month outcome measurement completeness | 6 months after surgery | 6-month outcome measurement \> 90% |
| Mean difference in total volume received | At time of surgery | A mean difference in total volume received (crystalloids and colloids combined) \> 1000 ml between groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Severe complications and graft lost | Up to 30 days or hospital discharge | Composite incidence of severe complication (Dindo-Clavien III or more) or graft lost (retransplantation or death) |
| Intraoperative blood loss | End of surgery | Intraoperative blood loss in mL |
| Intraoperative and perioperative blood product transfusions | From randomization up to 30 days or hospital discharge, whichever comes first | Total number of transfused units of labile and non-labile blood products (red blood cells, plasma, platelets, cryoprecipitates, fibrinogen, prothrombin complex concentrates) |
| 7-day quality of recovery | 7 days after surgery | 7-day quality of recovery measured using the QoR-15 (Quality of Recovery) tool |
| 7-day graft dysfunction | 7 days after surgery | 7-day graft dysfunction (definition as reported by Olthoff et al.) |
| 7-day AKI (grade 2 or 3) | 7 days after surgery | 7-day AKI grade 2 or 3 using the KDIGO (Kidney Disease: Improving Global Outcomes) definition |
| Any complication | From randomization up to 30 days or hospital discharge, whichever comes first | Any of the following complications, graded according to the Dindo-Clavien classification system: hemorrhagic, graft related, pulmonary, infectious or thromboembolic. |
| Any other severe complication | From randomization up to 30 days or hospital discharge, whichever comes first | Any other severe complication (Dindo-Clavien III or more) |
| Organ dysfunction and support | 30 days | 30-day organ support free days, using a recognized definition (as reported by Heyland et al.) |
| Intensive care unit (ICU) length of stay | From randomization up to hospital discharge (ascertained up to end of follow-up at 1 year) | Total duration of stay (days) in the intensive care unit (ICU) |
| Hospital length of stay | From randomization up to hospital discharge (ascertained up to end of follow-up at 1 year) | Total duration of stay (days) in the hospital |
| Quality of life (QoL) | 6 & 12 months after surgery | Quality of life (QoL) using the SF-36 tool |
| Hospital readmissions | From randomization up to 1 year after surgery | Hospital readmissions |
| Graft complications | From randomization up to 1 year after surgery | Graft complications |
| Survival | From randomization up to 1 year after surgery | Survival |
Countries
Canada
Contacts
PRINCIPAL_INVESTIGATORFrancois Martin Carrier, MD
Centre hospitalier université de Montréal
Outcome results
None listed