Restrictive Fluid Management In Liver Transplantation (REFIL)

NCT ID: NCT05647733

Last Updated: 2024-08-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-25
• Study Completion Date: 2026-01-01

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.

Conditions

Liver Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Restrictive group: Low splanchnic blood volume Restrictive fluid management strategy

The intervention group is targeted at lowering splanchnic blood volume using a phlebotomy and restricting fluid infusion, individualized to the physiological needs of this population and the distinct LT surgical phases. The strategy will first consist of performing a phlebotomy without fluid replacement at the start of surgery.We will combine it with fluid restriction to prevent excessive fluid administration and its effect on splanchnic blood volume and blood loss, combined with the effect of the phlebotomy, as well as to limit fluid overload, as previously reported. Fluid will be administered to compensate blood loss and treat severe hemodynamic instability.The phlebotomy will be transfused back at the beginning of the reperfusion phase where fluid management will be based on a goal-directed therapy (GDT) using either PPV or SV, as in the control group.

Group Type: EXPERIMENTAL

Low splanchnic blood volume restrictive fluid management strategy

Intervention Type: PROCEDURE

Hemodynamic goal-directed restrictive fluid management strategy.

Phlebotomy

Intervention Type: PROCEDURE

Retrieval of blood in a blood donation bag performed prior to dissection and transfused back after graft reperfusion

Liberal group: Optimized cardiac output liberal fluid management strategy

The control group will receive a liberal intraoperative fluid management strategy optimizing cardiac output throughout the surgery. It will consist of administering 250 mL fluid boluses until SV stops to increase by more than 10% or until PPV is below 12%, a dynamic indicator of fluid responsiveness validated in many surgical populations, including ESLD patients undergoing a LT.This strategy is informed by data from recent clinical trials on benefits of GDT in major surgery, data on strategies used in major surgery, liver resection or LT and our survey on current practice.

Group Type: ACTIVE_COMPARATOR

Optimized cardiac output liberal fluid management strategy

Intervention Type: PROCEDURE

Permissive intraoperative hemodynamic goal-directed fluid management strategy that optimizes cardiac output throughout surgery

Interventions

Low splanchnic blood volume restrictive fluid management strategy

Hemodynamic goal-directed restrictive fluid management strategy.

Intervention Type: PROCEDURE

Optimized cardiac output liberal fluid management strategy

Permissive intraoperative hemodynamic goal-directed fluid management strategy that optimizes cardiac output throughout surgery

Intervention Type: PROCEDURE

Phlebotomy

Retrieval of blood in a blood donation bag performed prior to dissection and transfused back after graft reperfusion

Intervention Type: PROCEDURE

Other Intervention Names

Restrictive arm; Liberal arm

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Canadian Donation and Transplantation Research Program (CDTRP)

UNKNOWN

Sponsor Role: collaborator

Canadian Perioperative Anesthesia Clinical Trial (PACT) Group

UNKNOWN

Sponsor Role: collaborator

Centre hospitalier de l'Université de Montréal (CHUM)

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francois-Martin Carrier, MD

Role: PRINCIPAL_INVESTIGATOR

Centre hospitalier université de Montréal

Locations

London Health Sciences Centre

London, Ontario, Canada

Site Status: RECRUITING

Centre Hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, Canada

Site Status: RECRUITING

McGill University Health Centre

Montreal, Quebec, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

François-Martin Carrier, MD

Role: CONTACT

francois.martin.carrier.med@ssss.gouv.qc.ca

514-890-8000

Martine Lebrasseur, RN

Role: CONTACT

martine.lebrasseur.chum@ssss.gouv.qc.ca

514-890-8000

Facility Contacts

Nelson Javier Gonzalez Valencia, MD

Role: primary

nelson.gonzalezvalencia@lhsc.on.ca

(519) 661-2111

François-Martin Carrier, MD

Role: primary

francois.martin.carrier.med@ssss.gouv.qc.ca

514-890-8000

Stanislas Kandelman, MD

Role: primary

stanislas.kandelman.med@ssss.gouv.qc.ca

(514)934-1934

Other Identifiers

2023-11173

Identifier Type: -

Identifier Source: org_study_id