Ta strona została przetłumaczona automatycznie i dokładność tłumaczenia nie jest gwarantowana. Proszę odnieść się do angielska wersja za tekst źródłowy.

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

8 lipca 2026 zaktualizowane przez: 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.

Przegląd badań

Status

Rekrutacyjny

Warunki

Interwencja / Leczenie

Szczegółowy opis

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).

Typ studiów

Interwencyjne

Zapisy (Szacowany)

866

Faza

  • Nie dotyczy

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Kontakt w sprawie studiów

Kopia zapasowa kontaktu do badania

Lokalizacje studiów

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

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

  • Dorosły
  • Starszy dorosły

Akceptuje zdrowych ochotników

Nie

Opis

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.

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Randomizowane
  • Model interwencyjny: Przydział równoległy
  • Maskowanie: Podwójnie

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: 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.
Procedura: Strategia restrykcyjnego zarządzania płynami z niską objętością krwi trzewnej
Strategia restrykcyjnego zarządzania płynami ukierunkowana na cel hemodynamiczny
Inne nazwy:
  • Ograniczający
Procedura: Phlebotomy
Blood drawn in a blood donation bag prior to dissection and transfused back after graft reperfusion
Aktywny 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.
Procedura: Optymalizowana strategia zarządzania płynami liberalnego rzutu serca
Permisywna strategia płynoterapii ukierunkowanej na cele hemodynamiczne, która optymalizuje rzut serca w trakcie zabiegu chirurgicznego
Inne nazwy:
  • Liberał

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Number of participants with at least one severe complication
Ramy czasowe: 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

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Number of participants who were transfused at least one unit of red blood cells (RBC) during the perioperative period of surgery
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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)
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

Centre hospitalier de l'Université de Montréal (CHUM)

Współpracownicy

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

Śledczy

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

Publikacje i pomocne linki

Osoba odpowiedzialna za wprowadzenie informacji o badaniu dobrowolnie udostępnia te publikacje. Mogą one dotyczyć wszystkiego, co jest związane z badaniem.

Publikacje ogólne

Przydatne linki

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów (Rzeczywisty)

15 lutego 2026

Zakończenie podstawowe (Szacowany)

1 listopada 2030

Ukończenie studiów (Szacowany)

1 listopada 2031

Daty rejestracji na studia

Pierwszy przesłany

15 czerwca 2026

Pierwszy przesłany, który spełnia kryteria kontroli jakości

8 lipca 2026

Pierwszy wysłany (Rzeczywisty)

10 lipca 2026

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

10 lipca 2026

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

8 lipca 2026

Ostatnia weryfikacja

1 czerwca 2026

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • 22.206

Plan dla danych uczestnika indywidualnego (IPD)

Planujesz udostępniać dane poszczególnych uczestników (IPD)?

NIE

Opis planu IPD

End-of-study knowledge translation (KT) planned

Informacje o lekach i urządzeniach, dokumenty badawcze

Bada produkt leczniczy regulowany przez amerykańską FDA

Nie

Bada produkt urządzenia regulowany przez amerykańską FDA

Nie

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

Subskrybuj