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.
연구 개요
상태
상세 설명
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).
연구 유형
등록 (추정된)
단계
- 해당 없음
연락처 및 위치
연구 연락처
- 이름: François Martin Carrier, MD
- 전화번호: 514-890-8000
- 이메일: francois.martin.carrier.med@ssss.gouv.qc.ca
연구 연락처 백업
- 이름: Manuela Mbacfou, MSc
- 전화번호: 31576 514-890-8000
- 이메일: manuela.mbacfou.temgoua.chum@ssss.gouv.qc.ca
연구 장소
-
-
British Columbia
-
Vancouver, British Columbia, 캐나다, V5Z 1M9
- 모병
- Vancouver General Hospital (VGH)
-
연락하다:
- JeiEung Park, MD
- 전화번호: 604-875-4111
- 이메일: jeieung.park@vch.ca
-
수석 연구원:
- JeiEung Park, MD
-
-
Ontario
-
London, Ontario, 캐나다, N6G 2V4
- 모병
- London Health Sciences Centre (LHSC)
-
수석 연구원:
- Nelson Javier Gonzalez Valencia, MD
-
연락하다:
- Nelson Javier Gonzalez Valencia, MD
- 전화번호: 519-661-2111
- 이메일: nelson.gonzalezvalencia@lhsc.on.ca
-
-
Quebec
-
Montreal, Quebec, 캐나다, H4A 3J1
- 모병
- McGill University Health Centre (MUHC)
-
연락하다:
- Stanislas Kandelman, MD
- 전화번호: 514-934-1934
- 이메일: stanislas.kandelman.med@ssss.gouv.qc.ca
-
수석 연구원:
- Stanislas Kandelman, MD
-
Montreal, Quebec, 캐나다, H2X 0C1
- 모병
- Centre hospitalier de l'Université de Montréal (CHUM)
-
부수사관:
- Michael Chassé, MD
-
연락하다:
- Manuela Mbacfou, MSc
- 전화번호: 31576 514-890-8000
- 이메일: manuela.mbacfou.temgoua.chum@ssss.gouv.qc.ca
-
수석 연구원:
- François Martin Carrier, MD
-
-
참여기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 더블
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: 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. |
혈역학적 목표 지향적 제한적 체액 관리 전략
다른 이름들:
Blood drawn in a blood donation bag prior to dissection and transfused back after graft reperfusion
|
|
활성 비교기: 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.
|
수술 전반에 걸쳐 심박출량을 최적화하는 허용적 혈역학 목표 지향적 체액 관리 전략
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Number of participants with at least one severe complication
기간: 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
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Number of participants who were transfused at least one unit of red blood cells (RBC) during the perioperative period of surgery
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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)
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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)
기간: 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)
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
|
공동 작업자 및 조사자
협력자
수사관
- 수석 연구원: François Martin Carrier, MD, Centre hospitalier de l'Université de Montréal (CHUM)
간행물 및 유용한 링크
일반 간행물
- 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.
유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- 22.206
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .