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Restrictive Fluid Management In Liver Transplantation (REFIL) (REFIL-2)

8. Juli 2026 aktualisiert von: Centre hospitalier de l'Université de Montréal (CHUM)

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: A Multicenter Randomized Controlled Trial (REFIL-2)

The goal of the REFIL-2 study is to evaluate the effectiveness of a low splanchnic blood volume restrictive fluid management strategy (a strategy that involves limiting fluid administration and prioritizing the use of medications that raise blood pressure during surgery, combined with phlebotomy) in improving patients' recovery after surgery. The study compares the low splanchnic blood volume restrictive fluid management strategy to an optimized cardiac-output liberal fluid management strategy (which involves administering more fluids to raise blood pressure with less reliance on medications). Outcomes important to patients will be measured.

This study (REFIL-2) had a vanguard phase (internal pilot) that included 138 patients (NCT05647733). The patients included in the vanguard pilot phase were not compared between groups but only analyzed descriptively using aggregated data. Only feasibility metrics were compared (see NCT05647733). These 138 patients were thus rolled into the REFIL-2 trial and included in the final sample size reported herein.

Studienübersicht

Status

Rekrutierung

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

People with advanced liver disease have poor blood circulation, and too much blood accumulates in the abdomen (a condition known as high intra-abdominal blood volume). However, liver transplantation (LT) is a complex surgery during which the patient can lose a significant amount of blood and blood pressure can fluctuate widely. Therefore, restricting fluids and using medications to raise blood pressure is a strategy that could reduce blood loss and potentially also certain complications after surgery. Furthermore, phlebotomy appears to reduce intra-abdominal blood volume, blood loss, drops in blood pressure, and the need for red blood cell transfusions, potentially improving recovery after surgery. This study therefore aims to determine the best way to manage fluids during a liver transplantation by comparing these two care strategies. Another goal of the study is to measure the cost-effectiveness of the proposed intervention.

Hypothesis: An intraoperative low splanchnic blood volume restrictive fluid management strategy is superior to an optimized cardiac-output liberal fluid management strategy in reducing postoperative severe complications after liver transplantation

Design: Multicenter blinded parallel arm randomized controlled trial

Study population: Adult patients undergoing a liver transplantation for end-stage liver disease (ESLD)

All participants will be followed during their index hospitalization up to post-transplantation Day 30 (whichever comes first), and for 12 months post-transplantation to assess some clinical outcomes, quality of life (QoL), and survival (being alive beyond the index hospitalization).

Participation in this study lasts 12 months.

The results of this study will help determine whether or not to recommend a low splanchnic blood volume restrictive fluid management strategy for people who undergo a liver transplantation.

This study is conducted in two phases: a pilot phase, which demonstrated feasibility across Canada, followed by the current larger-scale phase (REFIL-2).

Studientyp

Interventionell

Einschreibung (Geschätzt)

866

Phase

  • Unzutreffend

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienkontakt

Studieren Sie die Kontaktsicherung

Studienorte

  • Kanada
    • British Columbia
      • Vancouver, British Columbia, Kanada, V5Z 1M9
        • Rekrutierung
        • Vancouver General Hospital (VGH)
        • Kontakt:
        • Hauptermittler:
          • JeiEung Park, MD
    • Ontario
      • London, Ontario, Kanada, N6G 2V4
        • Rekrutierung
        • London Health Sciences Centre (LHSC)
        • Hauptermittler:
          • Nelson Javier Gonzalez Valencia, MD
        • Kontakt:
    • Quebec
      • Montreal, Quebec, Kanada, H4A 3J1
        • Rekrutierung
        • McGill University Health Centre (MUHC)
        • Kontakt:
        • Hauptermittler:
          • Stanislas Kandelman, MD
      • Montreal, Quebec, Kanada, H2X 0C1
        • Rekrutierung
        • Centre hospitalier de l'Université de Montréal (CHUM)
        • Unterermittler:
          • Michael Chassé, MD
        • Kontakt:
        • Hauptermittler:
          • François Martin Carrier, MD

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

  • Erwachsene
  • Älterer Erwachsener

Akzeptiert gesunde Freiwillige

Nein

Beschreibung

Inclusion Criteria:

  1. Adult ≥ 18 years old
  2. Undergoing liver transplantation (LT)
  3. End-stage liver disease (ESLD) (with or without hepatocellular carcinoma) as the indication for transplantation.

Exclusion Criteria:

  1. Undergoing LT for an indication other than ESLD (e.g., acute liver failure, primary liver cancer without ESLD, retransplantation, amyloid neuropathy, polycystic liver disease, or any other indication not associated with ESLD)
  2. Undergoing combined solid organ transplantations

  3. Any of the following conditions:

    • severe chronic renal failure (GFR < 15 ml/minute/1.73 m2 [CKD-EPI equation] or already on renal replacement therapy (RRT))
    • severe anemia (hemoglobin level < 80 g/L)
    • hemodynamic instability (norepinephrine equivalent > 10 ug/min)
  4. Physician refusal to enroll the patient.

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Parallele Zuordnung
  • Maskierung: Doppelt

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: Restrictive group - Low splanchnic blood volume restrictive fluid management strategy

A phlebotomy (a procedure where the patient's blood is drawn, similar to a blood donation, without fluid replacement) at the start of the surgery combined with fluid restriction (use of vasopressor preferentially to treat hemodynamic instability with tolerance to relative hypovolemia defined as a Pulse Pressure Variation (PPV) or Stroke Volume (SVV) up to 18%). Fluids will be administered to compensate for blood loss and/or treat severe hemodynamic instability.

Blood collected by phlebotomy will always be transfused back at the beginning of the reperfusion phase, during which fluid management will be based on goal-directed therapy (GDT) using either PPV or SV, as in the control group.
Verfahren: Strategie zur restriktiven Flüssigkeitsverabreichung mit niedrigem splanchnischem Blutvolumen
Hämodynamisch zielgerichtete restriktive Flüssigkeitsmanagement-Strategie
Andere Namen:
  • Restriktiv
Verfahren: Phlebotomy
Blood drawn in a blood donation bag prior to dissection and transfused back after graft reperfusion
Aktiver Komparator: Liberal group - Optimized cardiac output liberal fluid management strategy
Goal-directed therapy (GDT): Patients will receive 250 ml fluid boluses until SV stops increasing by more than 10% or until PPV is below 12%. Fluids will thus be used preferentially to treat hemodynamic instability. Fluids will also be administered to compensate for blood loss and/or treat severe hemodynamic instability.
Verfahren: Optimierte kardiale Auswurf liberale Flüssigkeitsmanagement-Strategie
Permissive hämodynamische zielgerichtete Flüssigkeitsmanagementstrategie, die das Herzzeitvolumen während der gesamten Operation optimiert
Andere Namen:
  • Liberale

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Number of participants with at least one severe complication
Zeitfenster: Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first
Incidence of at least one severe complications defined as a complication of grade ≥ 3 according to the Dindo-Clavien scale (grade 1 to 5)
Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Number of participants who were transfused at least one unit of red blood cells (RBC) during the perioperative period of surgery
Zeitfenster: During surgery (from entrance in the operating to exit of the operating room) and up to 48 hours after surgery (from exit of the operating room to 48 hours after exit of the operating room)
Incidence of participants transfused at least 1 unit of RBC during the perioperative period of surgery
During surgery (from entrance in the operating to exit of the operating room) and up to 48 hours after surgery (from exit of the operating room to 48 hours after exit of the operating room)
Number of participants who were transfused at least one unit of red blood cells (RBC) during surgery
Zeitfenster: Intraoperative (from entrance in the operating room to exit of the operating room)
Incidence of at least one RBC transfusion during surgery
Intraoperative (from entrance in the operating room to exit of the operating room)
Intraoperative blood loss
Zeitfenster: Intraoperative (from entrance in the operating room to exit of the operating room)
Blood loss as estimated by clinicians
Intraoperative (from entrance in the operating room to exit of the operating room)
7-day quality of recovery
Zeitfenster: One time point: 7 days after surgery (transplantation)
Quality of recovery measured using the 15-item Quality of Recovery (QoR-15) score. Each item is scored on an 11-point numerical rating scale (0-10) for a total between 0 and 150, 0 being the worst possible recovery and 150 being a perfect recovery.
One time point: 7 days after surgery (transplantation)
Number of participants with a 7-day graft dysfunction
Zeitfenster: One time point: 7 days after surgery (transplantation)
Incidence of graft dysfunction (as per Olthoff's definition)
One time point: 7 days after surgery (transplantation)
Number of participants with a 7-day acute kidney injury (AKI)
Zeitfenster: Over 7 days after surgery (criteria met at any day from surgery to day 7 after surgery)
Acute kidney injury (AKI) of KDIGO grade 2 or 3
Over 7 days after surgery (criteria met at any day from surgery to day 7 after surgery)
Number of participants who were transfused at least one unit of red blood cells (RBC) up to hospital discharge
Zeitfenster: From surgery to hospital discharge (from entrance in the operating room to hospital discharge) or 30 days, whichever comes first
Incidence of at least one RBC transfusion from surgery to hospital discharge
From surgery to hospital discharge (from entrance in the operating room to hospital discharge) or 30 days, whichever comes first
Number of participants who were transfused at least one unit of any labile blood product up to hospital discharge
Zeitfenster: From surgery to hospital discharge (from entrance in the operating room to hospital discharge) or 30 days, whichever comes first
Incidence of at least one labile blood product transfused from surgery up to hospital discharge
From surgery to hospital discharge (from entrance in the operating room to hospital discharge) or 30 days, whichever comes first
Number of participants with at least one postoperative hemorrhagic complication up to hospital discharge
Zeitfenster: Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first
Incidence of at least one postoperative hemorrhagic complication, defined as any bleeding episode associated with a drop of hemoglobin of 20 g/L within 24 hours of bleeding, requiring 2 blood units within 24 hours of bleeding, a surgical hemostasis or an angioembolization.
Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first
Number of participants with postoperative acute kidney injury (AKI) up to hospital discharge
Zeitfenster: Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first
Incidence of any postoperative acute kidney injury (AKI) (any grade as per KDIGO criteria) up to hospital discharge
Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first
Number of participants requiring renal replacement therapy (RRT) up to hospital discharge
Zeitfenster: Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first
Incidence of postoperative requirement for renal replacement therapy (RRT) [hemodialysis or hemofiltration] up to hospital discharge
Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first
Number of participants with at least one postoperative graft complication up to hospital discharge
Zeitfenster: Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first
Incidence of at least one postoperative graft complication (primary non-function, vascular, biliary) or retransplantation up to hospital discharge
Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first
Number of participants with at least one postoperative infectious complication up to hospital discharge
Zeitfenster: Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first
Incidence of any postoperative infectious complication (other than pneumonia) up to hospital discharge
Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first
Number of patients with a postoperative wound dehiscence up to hospital discharge
Zeitfenster: Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first
Incidence of postoperative wound dehiscence or evisceration up to hospital discharge
Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first
Number of patients with at least one postoperative pulmonary complication up to hospital discharge
Zeitfenster: Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first
Incidence of any postoperative pulmonary complications (atelectasis, pneumonia, pulmonary oedema) up to hospital discharge
Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first
Number of participants with at least one postoperative thromboembolic complication up to hospital discharge
Zeitfenster: Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first
Incidence of at least one thromboembolic complication (deep vein thrombosis, pulmonary embolism, myocardial infraction, stroke, mesenteric ischemia) up to hospital discharge
Up to hospital discharge (from surgery to hospital discharge) or 30 days, whichever comes first
Number of participants with a postoperative ICU readmission up to hospital discharge
Zeitfenster: From initial ICU discharge (planned postoperative ICU or step-down unit admission) to hospital discharge or 30 days, whichever comes first
Incidence of ICU readmissions after initial discharge (from the planned postoperative ICU or step-down unit admission) to hospital discharge
From initial ICU discharge (planned postoperative ICU or step-down unit admission) to hospital discharge or 30 days, whichever comes first
Number of days not in an intensive care unit (ICU) at 30 days after surgery (30-day ICU-free days over 30 days)
Zeitfenster: From surgery to 30 days after surgery

Number of days alive and not hospitalized in an ICU.

0 means 30 consecutive days in the ICU or death within 30 days without any day without being in an ICU from surgery to death.

30 means no days hospitalized in an ICU from surgery to the 30-day time point.
From surgery to 30 days after surgery
Number of days without organ support at 30 days after surgery (30-day organ support free days)
Zeitfenster: From surgery to 30 days after surgery

Number of days alive without renal replacement therapy, mechanical ventilation or vasopressor 30 days after surgery.

0 means 30 consecutive days with any organ support or death within 30 days without any day without organ support from surgery to death.

30 means no days with organ support from surgery to the 30-day time point.
From surgery to 30 days after surgery
Hospital length of stay
Zeitfenster: From surgery to hospital discharge (up to 12 months after surgery)
Length of hospital stay (days)
From surgery to hospital discharge (up to 12 months after surgery)
Quality of life score
Zeitfenster: Two time points: 6 and 12 months after surgery
Quality of life (QoL) score using the 36-item Short Form health survey questionnaire (SF-36). Score ranges from 0 (worst possible health) to 100 (best possible health).
Two time points: 6 and 12 months after surgery
Rate of hospital readmissions
Zeitfenster: From hospital discharge after surgery to 12 months after surgery
Number of postoperative hospital readmissions over 12 months after surgery
From hospital discharge after surgery to 12 months after surgery
Rate of 1-year graft complications
Zeitfenster: From surgery to 12 months after surgery
Time to any graft complication (vascular or biliary) to 1 year after surgery
From surgery to 12 months after surgery
Rate of 1-year graft survival
Zeitfenster: From surgery to 12 months after surgery

Time to graft lost (death of retransplantation) up to 1 year after surgery.

Censoring will occur if lost to follow-up or 1 year after surgery.
From surgery to 12 months after surgery
Rate of 1-year recipient survival
Zeitfenster: From surgery to 12 months after surgery.

Time to death up to 1 year after surgery.

Censoring will occur if lost to follow-up or at 12 months after surgery.
From surgery to 12 months after surgery.
Costs of the intervention
Zeitfenster: Up to 12 months post-transplantation
Complication-related costs (total and subcomponent costs including complications, ressource utilization and hospital readmissions)
Up to 12 months post-transplantation

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Centre hospitalier de l'Université de Montréal (CHUM)

Mitarbeiter

Canadian Institutes of Health Research (CIHR)
Canadian Donation and Transplantation Research Program (CDTRP)
Canadian Perioperative Anesthesia Clinical Trial (PACT) Group

Ermittler

  • Hauptermittler: François Martin Carrier, MD, Centre hospitalier de l'Université de Montréal (CHUM)

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Allgemeine Veröffentlichungen

Nützliche Links

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Tatsächlich)

15. Februar 2026

Primärer Abschluss (Geschätzt)

1. November 2030

Studienabschluss (Geschätzt)

1. November 2031

Studienanmeldedaten

Zuerst eingereicht

15. Juni 2026

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

8. Juli 2026

Zuerst gepostet (Tatsächlich)

10. Juli 2026

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

10. Juli 2026

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

8. Juli 2026

Zuletzt verifiziert

1. Juni 2026

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • 22.206

Plan für individuelle Teilnehmerdaten (IPD)

Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?

NEIN

Beschreibung des IPD-Plans

End-of-study knowledge translation (KT) planned

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt

Nein

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

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