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

8 luglio 2026 aggiornato da: 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.

Panoramica dello studio

Stato

Reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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).

Tipo di studio

Interventistico

Iscrizione (Stimato)

866

Fase

  • Non applicabile

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Backup dei contatti dello studio

Luoghi di studio

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

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Adulto
  • Adulto più anziano

Accetta volontari sani

No

Descrizione

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.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Doppio

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 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 di gestione restrittiva dei fluidi con basso volume ematico splancnico
Strategia di gestione restrittiva dei fluidi guidata dall'obiettivo emodinamico
Altri nomi:
  • Restrittivo
Procedura: Phlebotomy
Blood drawn in a blood donation bag prior to dissection and transfused back after graft reperfusion
Comparatore attivo: 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: Strategia di gestione liberale dei liquidi con gittata cardiaca ottimizzata
Strategia permissiva di gestione dei fluidi basata su obiettivi emodinamici che ottimizza la gittata cardiaca durante l'intervento chirurgico
Altri nomi:
  • Liberale

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Number of participants with at least one severe complication
Lasso di tempo: 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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Number of participants who were transfused at least one unit of red blood cells (RBC) during the perioperative period of surgery
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Centre hospitalier de l'Université de Montréal (CHUM)

Collaboratori

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

Investigatori

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

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Collegamenti utili

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

15 febbraio 2026

Completamento primario (Stimato)

1 novembre 2030

Completamento dello studio (Stimato)

1 novembre 2031

Date di iscrizione allo studio

Primo inviato

15 giugno 2026

Primo inviato che soddisfa i criteri di controllo qualità

8 luglio 2026

Primo Inserito (Effettivo)

10 luglio 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

10 luglio 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

8 luglio 2026

Ultimo verificato

1 giugno 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 22.206

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Descrizione del piano IPD

End-of-study knowledge translation (KT) planned

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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