Restrictive Fluid Management In Liver Transplantation (REFIL)

Sponsor

Centre hospitalier de l'Université de Montréal (CHUM) (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05647733

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Liver Transplantation	Procedure: Low splanchnic blood volume Restrictive fluid management strategy vs Optimized cardiac output liberal fluid management strategy	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

72 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Care Provider)

Masking Description:

Only the anesthesiology team will know the allocation received since they must implement the intervention, limiting differential outcome classification bias since they will not assess outcomes. Patients, surgeons, and non-anesthesia health professionals will be blinded to allocation.

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Jan 1, 2025

Anticipated Study Completion Date :

Jan 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Intervention 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.	Procedure: Low splanchnic blood volume Restrictive fluid management strategy vs Optimized cardiac output liberal fluid management strategy 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.
Sham Comparator: Control 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.	Procedure: Low splanchnic blood volume Restrictive fluid management strategy vs Optimized cardiac output liberal fluid management strategy 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.

Arm

Intervention/Treatment

Active Comparator: Intervention 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.

Procedure: Low splanchnic blood volume Restrictive fluid management strategy vs Optimized cardiac output liberal fluid management strategy

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.

Sham Comparator: Control 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.

Procedure: Low splanchnic blood volume Restrictive fluid management strategy vs Optimized cardiac output liberal fluid management strategy

Outcome Measures

Primary Outcome Measures

STUDY FEASIBILITY,RECRUITMENT RATE ≥ 4 PATIENTS/MONTH [through study completion, an average of 3 year]
The main outcomes of this pilot study concern feasibility.Our primary outcome will be an overall recruitment rate ≥ 4 patients/month across all sites, a rate necessary to complete a final efficacy trial within a reasonable period after the start of the pilot based on sites' annual transplant volume.
PROTOCOL ADHERENCE > 90% [through study completion, an average of 3 year]
a protocol adherence > 90%; a 30 days or hospital discharge and 6-month outcome measurement > 90%; a mean difference in total volume received (crystalloids and colloids combined) > 1000 ml between groups.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	London Health Sciences Centre	London	Ontario	Canada	N6G 2V4
2	Centre Hospitalier de l'Université de Montréal (CHUM)	Montréal	Quebec	Canada	H2X 0C1
3	McGill University Health Centre	Montréal	Quebec	Canada	H4A 3J1

Sponsors and Collaborators

Centre hospitalier de l'Université de Montréal (CHUM)

Investigators

Principal Investigator: Francois-Martin Carrier, MD, Centre hospitalier université de Montréal

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Centre hospitalier de l'Université de Montréal (CHUM)

ClinicalTrials.gov Identifier:

NCT05647733

Other Study ID Numbers:

2023-11173

First Posted:

Dec 12, 2022

Last Update Posted:

Dec 15, 2022

Last Verified:

Dec 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Study Results

No Results Posted as of Dec 15, 2022