Restrictive Fluid Management In Liver Transplantation (REFIL) (REFIL-2)
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.
Visão geral do estudo
Status
Descrição detalhada
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 de estudo
Inscrição (Estimado)
Estágio
- Não aplicável
Contactos e Locais
Contato de estudo
- Nome: François Martin Carrier, MD
- Número de telefone: 514-890-8000
- E-mail: francois.martin.carrier.med@ssss.gouv.qc.ca
Estude backup de contato
- Nome: Manuela Mbacfou, MSc
- Número de telefone: 31576 514-890-8000
- E-mail: manuela.mbacfou.temgoua.chum@ssss.gouv.qc.ca
Locais de estudo
-
-
British Columbia
-
Vancouver, British Columbia, Canadá, V5Z 1M9
- Recrutamento
- Vancouver General Hospital (VGH)
-
Contato:
- JeiEung Park, MD
- Número de telefone: 604-875-4111
- E-mail: jeieung.park@vch.ca
-
Investigador principal:
- JeiEung Park, MD
-
-
Ontario
-
London, Ontario, Canadá, N6G 2V4
- Recrutamento
- London Health Sciences Centre (LHSC)
-
Investigador principal:
- Nelson Javier Gonzalez Valencia, MD
-
Contato:
- Nelson Javier Gonzalez Valencia, MD
- Número de telefone: 519-661-2111
- E-mail: nelson.gonzalezvalencia@lhsc.on.ca
-
-
Quebec
-
Montreal, Quebec, Canadá, H4A 3J1
- Recrutamento
- McGill University Health Centre (MUHC)
-
Contato:
- Stanislas Kandelman, MD
- Número de telefone: 514-934-1934
- E-mail: stanislas.kandelman.med@ssss.gouv.qc.ca
-
Investigador principal:
- Stanislas Kandelman, MD
-
Montreal, Quebec, Canadá, H2X 0C1
- Recrutamento
- Centre hospitalier de l'Université de Montréal (CHUM)
-
Subinvestigador:
- Michael Chassé, MD
-
Contato:
- Manuela Mbacfou, MSc
- Número de telefone: 31576 514-890-8000
- E-mail: manuela.mbacfou.temgoua.chum@ssss.gouv.qc.ca
-
Investigador principal:
- François Martin Carrier, MD
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Descrição
Inclusion Criteria:
- Adult ≥ 18 years old
- Undergoing liver transplantation (LT)
- End-stage liver disease (ESLD) (with or without hepatocellular carcinoma) as the indication for transplantation.
Exclusion Criteria:
- 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)
- Undergoing combined solid organ transplantations
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)
- Physician refusal to enroll the patient.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Dobro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
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. |
Estratégia de gestão restritiva de fluidos guiada por objetivos hemodinâmicos
Outros nomes:
Blood drawn in a blood donation bag prior to dissection and transfused back after graft reperfusion
|
|
Comparador Ativo: 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.
|
Estratégia permissiva de gestão de fluidos orientada por objetivos hemodinâmicos que otimiza o débito cardíaco durante toda a cirurgia
Outros nomes:
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Number of participants with at least one severe complication
Prazo: 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
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Number of participants who were transfused at least one unit of red blood cells (RBC) during the perioperative period of surgery
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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)
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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)
Prazo: 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)
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
|
Colaboradores e Investigadores
Colaboradores
Investigadores
- Investigador principal: François Martin Carrier, MD, Centre hospitalier de l'Université de Montréal (CHUM)
Publicações e links úteis
Publicações Gerais
- Parikh A, Washburn KW, Matsuoka L, Pandit U, Kim JE, Almeda J, Mora-Esteves C, Halff G, Genyk Y, Holland B, Wilson DJ, Sher L, Koneru B. A multicenter study of 30 days complications after deceased donor liver transplantation in the model for end-stage liver disease score era. Liver Transpl. 2015 Sep;21(9):1160-8. doi: 10.1002/lt.24181.
- Thacker JK, Mountford WK, Ernst FR, Krukas MR, Mythen MM. Perioperative Fluid Utilization Variability and Association With Outcomes: Considerations for Enhanced Recovery Efforts in Sample US Surgical Populations. Ann Surg. 2016 Mar;263(3):502-10. doi: 10.1097/SLA.0000000000001402.
- Shin CH, Long DR, McLean D, Grabitz SD, Ladha K, Timm FP, Thevathasan T, Pieretti A, Ferrone C, Hoeft A, Scheeren TWL, Thompson BT, Kurth T, Eikermann M. Effects of Intraoperative Fluid Management on Postoperative Outcomes: A Hospital Registry Study. Ann Surg. 2018 Jun;267(6):1084-1092. doi: 10.1097/SLA.0000000000002220.
- Carrier FM, Chasse M, Wang HT, Aslanian P, Iorio S, Bilodeau M, Turgeon AF. Restrictive fluid management strategies and outcomes in liver transplantation: a systematic review. Can J Anaesth. 2020 Jan;67(1):109-127. doi: 10.1007/s12630-019-01480-y. Epub 2019 Sep 25.
Links úteis
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças do aparelho digestivo
- Insuficiência hepática
- Insuficiência Hepática
- Doenças do Fígado
- Doença hepática terminal
- Técnicas de investigação
- Terapêutica
- Manipulação de amostras
- Técnicas de laboratório clínico
- Técnicas e procedimentos de diagnóstico
- Diagnóstico
- Perfurações
- Procedimentos cirúrgicos, operatórios
- Coleção de amostras de sangue
- Flebotomia
Outros números de identificação do estudo
- 22.206
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .