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.
調査の概要
状態
詳細な説明
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).
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：François Martin Carrier, MD
- 電話番号：514-890-8000
- メール：francois.martin.carrier.med@ssss.gouv.qc.ca
研究連絡先のバックアップ
- 名前：Manuela Mbacfou, MSc
- 電話番号：31576 514-890-8000
- メール：manuela.mbacfou.temgoua.chum@ssss.gouv.qc.ca
研究場所
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British Columbia
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Vancouver、British Columbia、カナダ、V5Z 1M9
- 募集
- Vancouver General Hospital (VGH)
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コンタクト：
- JeiEung Park, MD
- 電話番号：604-875-4111
- メール：jeieung.park@vch.ca
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主任研究者：
- JeiEung Park, MD
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Ontario
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London、Ontario、カナダ、N6G 2V4
- 募集
- London Health Sciences Centre (LHSC)
-
主任研究者：
- Nelson Javier Gonzalez Valencia, MD
-
コンタクト：
- Nelson Javier Gonzalez Valencia, MD
- 電話番号：519-661-2111
- メール：nelson.gonzalezvalencia@lhsc.on.ca
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Quebec
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Montreal、Quebec、カナダ、H4A 3J1
- 募集
- McGill University Health Centre (MUHC)
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コンタクト：
- Stanislas Kandelman, MD
- 電話番号：514-934-1934
- メール：stanislas.kandelman.med@ssss.gouv.qc.ca
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主任研究者：
- Stanislas Kandelman, MD
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Montreal、Quebec、カナダ、H2X 0C1
- 募集
- Centre hospitalier de l'Université de Montréal (CHUM)
-
副調査官：
- Michael Chassé, MD
-
コンタクト：
- Manuela Mbacfou, MSc
- 電話番号：31576 514-890-8000
- メール：manuela.mbacfou.temgoua.chum@ssss.gouv.qc.ca
-
主任研究者：
- François Martin Carrier, MD
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-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：ダブル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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. |
血行動態に基づく目標指向的制限的輸液管理戦略
他の名前：
Blood drawn in a blood donation bag prior to dissection and transfused back after graft reperfusion
|
|
アクティブコンパレータ：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.
|
手術全体を通して心拍出量を最適化する寛容な血行動態目標指向型輸液管理戦略
他の名前：
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Number of participants with at least one severe complication
時間枠：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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Number of participants who were transfused at least one unit of red blood cells (RBC) during the perioperative period of surgery
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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)
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
|
協力者と研究者
協力者
捜査官
- 主任研究者：François Martin Carrier, MD、Centre hospitalier de l'Université de Montréal (CHUM)
出版物と役立つリンク
一般刊行物
- 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.
便利なリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 22.206
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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