Restrictive Fluid Management In Liver Transplantation (REFIL)

Liver Transplantation Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05647733
• Other study ID #: 2023-11173
• Status: Recruiting
• Phase: N/A
• Start date: April 25, 2023
• Est. completion date: January 2026

Study information

• Verified date: June 2023
• Source: Centre hospitalier de l'Université de Montréal (CHUM)
• Contact: François-Martin Carrier, MD
• Phone: 514-890-8000
• Email: francois.martin.carrier.med[@]ssss.gouv.qc.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: January 2026
• Est. primary completion date: January 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Liver Transplantation

Intervention

Procedure:
• Low splanchnic blood volume restrictive fluid management strategy
Hemodynamic goal-directed restrictive fluid management strategy.
• Optimized cardiac output liberal fluid management strategy
Permissive intraoperative hemodynamic goal-directed fluid management strategy that optimizes cardiac output throughout surgery
• Phlebotomy
Retrieval of blood in a blood donation bag performed prior to dissection and transfused back after graft reperfusion

Locations

Country	Name	City	State
Canada	London Health Sciences Centre	London	Ontario
Canada	Centre Hospitalier de l'Université de Montréal (CHUM)	Montréal	Quebec
Canada	McGill University Health Centre	Montréal	Quebec

Sponsors (4)

Lead Sponsor	Collaborator
Centre hospitalier de l'Université de Montréal (CHUM)	Canadian Donation and Transplantation Research Program (CDTRP), Canadian Institutes of Health Research (CIHR), Canadian Perioperative Anesthesia Clinical Trial (PACT) Group

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recruitment rate	Overall recruitment rate = 4 patients/month (across all sites)	18 months (at study level)
Primary	Adherence	Protocol adherence > 90%, defined using a questionnaire	At time of surgery
Primary	Hospital outcome measurement completeness	A 30 days or hospital discharge outcome measurement > 90%	At 30 days (or hospital discharge) after surgery
Primary	6-month outcome measurement completeness	6-month outcome measurement > 90%	6 months after surgery
Primary	Mean difference in total volume received	A mean difference in total volume received (crystalloids and colloids combined) > 1000 ml between groups.	At time of surgery
Secondary	Severe complications and graft lost	Composite incidence of severe complication (Dindo-Clavien III or more) or graft lost (retransplantation or death)	Up to 30 days or hospital discharge
Secondary	Intraoperative blood loss	Intraoperative blood loss in mL	End of surgery
Secondary	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)	From randomization up to 30 days or hospital discharge, whichever comes first
Secondary	7-day quality of recovery	7-day quality of recovery measured using the QoR-15 (Quality of Recovery) tool	7 days after surgery
Secondary	7-day graft dysfunction	7-day graft dysfunction (definition as reported by Olthoff et al.)	7 days after surgery
Secondary	7-day AKI (grade 2 or 3)	7-day AKI grade 2 or 3 using the KDIGO (Kidney Disease: Improving Global Outcomes) definition	7 days after surgery
Secondary	Any complication	Any of the following complications, graded according to the Dindo-Clavien classification system: hemorrhagic, graft related, pulmonary, infectious or thromboembolic.	From randomization up to 30 days or hospital discharge, whichever comes first
Secondary	Any other severe complication	Any other severe complication (Dindo-Clavien III or more)	From randomization up to 30 days or hospital discharge, whichever comes first
Secondary	Organ dysfunction and support	30-day organ support free days, using a recognized definition (as reported by Heyland et al.)	30 days
Secondary	Intensive care unit (ICU) length of stay	Total duration of stay (days) in the intensive care unit (ICU)	From randomization up to hospital discharge (ascertained up to end of follow-up at 1 year)
Secondary	Hospital length of stay	Total duration of stay (days) in the hospital	From randomization up to hospital discharge (ascertained up to end of follow-up at 1 year)
Secondary	Quality of life (QoL)	Quality of life (QoL) using the SF-36 tool	6 & 12 months after surgery
Secondary	Hospital readmissions	Hospital readmissions	From randomization up to 1 year after surgery
Secondary	Graft complications	Graft complications	From randomization up to 1 year after surgery
Secondary	Survival	Survival	From randomization up to 1 year after surgery