Ignite Creation Date:
2025-12-25 @ 2:41 AM
Ignite Modification Date:
2026-02-27 @ 10:55 PM
Study NCT ID:
NCT05647733
Status:
RECRUITING
Last Update Posted:
2024-08-22
First Post:
2022-11-30
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Restrictive Fluid Management In Liver Transplantation (REFIL)
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D018962', 'term': 'Phlebotomy'}], 'ancestors': [{'id': 'D001800', 'term': 'Blood Specimen Collection'}, {'id': 'D013048', 'term': 'Specimen Handling'}, {'id': 'D019411', 'term': 'Clinical Laboratory Techniques'}, {'id': 'D019937', 'term': 'Diagnostic Techniques and Procedures'}, {'id': 'D003933', 'term': 'Diagnosis'}, {'id': 'D011677', 'term': 'Punctures'}, {'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}, {'id': 'D008919', 'term': 'Investigative Techniques'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR'], 'maskingDescription': 'Only the anesthesiology team will know the allocation received since they must implement the intervention, limiting differential outcome classification bias since they will not assess outcomes. Patients, surgeons, and non-anesthesia health professionals will be blinded to allocation.'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Participants will be allocated to either group in a 1:1 ratio. A research assistant will randomize the patient once a viable graft is confirmed, and then share allocation with the anesthesiology team.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 72}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2023-04-25', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-08', 'completionDateStruct': {'date': '2026-01-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-08-21', 'studyFirstSubmitDate': '2022-11-30', 'studyFirstSubmitQcDate': '2022-12-08', 'lastUpdatePostDateStruct': {'date': '2024-08-22', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2022-12-12', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-01-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Recruitment rate', 'timeFrame': '18 months (at study level)', 'description': 'Overall recruitment rate ≥ 4 patients/month (across all sites)'}, {'measure': 'Adherence', 'timeFrame': 'At time of surgery', 'description': 'Protocol adherence \\> 90%, defined using a questionnaire'}, {'measure': 'Hospital outcome measurement completeness', 'timeFrame': 'At 30 days (or hospital discharge) after surgery', 'description': 'A 30 days or hospital discharge outcome measurement \\> 90%'}, {'measure': '6-month outcome measurement completeness', 'timeFrame': '6 months after surgery', 'description': '6-month outcome measurement \\> 90%'}, {'measure': 'Mean difference in total volume received', 'timeFrame': 'At time of surgery', 'description': 'A mean difference in total volume received (crystalloids and colloids combined) \\> 1000 ml between groups.'}], 'secondaryOutcomes': [{'measure': 'Severe complications and graft lost', 'timeFrame': 'Up to 30 days or hospital discharge', 'description': 'Composite incidence of severe complication (Dindo-Clavien III or more) or graft lost (retransplantation or death)'}, {'measure': 'Intraoperative blood loss', 'timeFrame': 'End of surgery', 'description': 'Intraoperative blood loss in mL'}, {'measure': 'Intraoperative and perioperative blood product transfusions', 'timeFrame': 'From randomization up to 30 days or hospital discharge, whichever comes first', 'description': 'Total number of transfused units of labile and non-labile blood products (red blood cells, plasma, platelets, cryoprecipitates, fibrinogen, prothrombin complex concentrates)'}, {'measure': '7-day quality of recovery', 'timeFrame': '7 days after surgery', 'description': '7-day quality of recovery measured using the QoR-15 (Quality of Recovery) tool'}, {'measure': '7-day graft dysfunction', 'timeFrame': '7 days after surgery', 'description': '7-day graft dysfunction (definition as reported by Olthoff et al.)'}, {'measure': '7-day AKI (grade 2 or 3)', 'timeFrame': '7 days after surgery', 'description': '7-day AKI grade 2 or 3 using the KDIGO (Kidney Disease: Improving Global Outcomes) definition'}, {'measure': 'Any complication', 'timeFrame': 'From randomization up to 30 days or hospital discharge, whichever comes first', 'description': 'Any of the following complications, graded according to the Dindo-Clavien classification system: hemorrhagic, graft related, pulmonary, infectious or thromboembolic.'}, {'measure': 'Any other severe complication', 'timeFrame': 'From randomization up to 30 days or hospital discharge, whichever comes first', 'description': 'Any other severe complication (Dindo-Clavien III or more)'}, {'measure': 'Organ dysfunction and support', 'timeFrame': '30 days', 'description': '30-day organ support free days, using a recognized definition (as reported by Heyland et al.)'}, {'measure': 'Intensive care unit (ICU) length of stay', 'timeFrame': 'From randomization up to hospital discharge (ascertained up to end of follow-up at 1 year)', 'description': 'Total duration of stay (days) in the intensive care unit (ICU)'}, {'measure': 'Hospital length of stay', 'timeFrame': 'From randomization up to hospital discharge (ascertained up to end of follow-up at 1 year)', 'description': 'Total duration of stay (days) in the hospital'}, {'measure': 'Quality of life (QoL)', 'timeFrame': '6 & 12 months after surgery', 'description': 'Quality of life (QoL) using the SF-36 tool'}, {'measure': 'Hospital readmissions', 'timeFrame': 'From randomization up to 1 year after surgery', 'description': 'Hospital readmissions'}, {'measure': 'Graft complications', 'timeFrame': 'From randomization up to 1 year after surgery', 'description': 'Graft complications'}, {'measure': 'Survival', 'timeFrame': 'From randomization up to 1 year after surgery', 'description': 'Survival'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Hemodynamic management', 'Fluid management', 'Transfusions', 'Phlebotomy'], 'conditions': ['Liver Transplantation']}, 'descriptionModule': {'briefSummary': 'Hypothesis: A Canadian multicentre clinical trial is feasible. Study Design: Multicenter internal pilot parallel arm randomized controlled trial\n\nStudy population: Patients with end-stage liver disease undergoing a liver transplantation not meeting any exclusion criteria.\n\nPrimary endpoint: The primary feasibility endpoint is an overall recruitment rate ≥ 4 patients/month across all three participating sites.\n\nSecondary endpoint: The secondary feasibility endpoints are a protocol adherence \\> 90%, a 30-day (or hospital discharge) and 6-month outcome measurement \\> 90%, and a mean difference in total intraoperative volume received (crystalloids and colloids combined) \\> 1000 ml between groups.\n\nStudy intervention: Low splanchnic blood volume restrictive fluid management strategy (intervention). A phlebotomy, performed prior to dissection and transfused back after graft reperfusion, combined with a hemodynamic goal-directed restrictive fluid management strategy\n\nOptimized cardiac-output liberal fluid management strategy (control) A hemodynamic goal-directed liberal fluid management strategy that optimizes cardiac output throughout surgery', 'detailedDescription': 'MAIN OBJECTIVE The main objective of the REFIL-1 pilot study is to establish the feasibility (recruitment, adherence, outcome measurement) of conducting a Canadian multicentre randomized controlled trial comparing an intraoperative low-splanchnic blood volume restrictive fluid management strategy to a cardiac output optimised liberal fluid management strategy in adult LT for ESLD. The hypothesis is that a Canadian multicentre clinical trial is feasible.\n\nSECONDARY OBJECTIVES The overarching objective of the ReFIL (Restrictive Fluid management In Liver transplantation) research program, which will be answered in a future large-scale trial, regards the efficacy of the proposed interventional strategy to improve postoperative outcomes in LT.\n\nTERTIARY OBJECTIVES Our tertiary objective is to measure the cost-effectiveness of the proposed intervention based on the composite outcome of any severe postoperative complications and graft loss.\n\nDESIGN AND STUDY POPULATION This study a multicentre internal pilot parallel arm randomized trial comparing two intraoperative hemodynamic and splanchnic blood volume management strategies in LT recipients.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Any adult patient ≥ 18 years of age undergoing liver transplantation for ESLD.\n\nExclusion Criteria:\n\n* Patients undergoing LT for an indication other than ESLD such as acute liver failure, liver cancer without ESLD, retransplantation, amyloid neuropathy or any other indication not associated with ESLD.\n* Patients undergoing a combined liver and lung or liver and heart transplantation.\n* Patients with any of the following conditions:\n* severe chronic renal failure (GFR \\< 15 ml/minute/1.73 m2 \\[CKD-EPI equation\\] or already on RRT);\n* severe anemia (hemoglobin level \\< 80 g/L);76,93,109\n* hemodynamic instability (norepinephrine equivalent \\> 10 ug/min).'}, 'identificationModule': {'nctId': 'NCT05647733', 'acronym': 'REFIL', 'briefTitle': 'Restrictive Fluid Management In Liver Transplantation (REFIL)', 'organization': {'class': 'OTHER', 'fullName': "Centre hospitalier de l'Université de Montréal (CHUM)"}, 'officialTitle': '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', 'orgStudyIdInfo': {'id': '2023-11173'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Restrictive group: Low splanchnic blood volume Restrictive fluid management strategy', 'description': 'The intervention group is targeted at lowering splanchnic blood volume using a phlebotomy and restricting fluid infusion, individualized to the physiological needs of this population and the distinct LT surgical phases. The strategy will first consist of performing a phlebotomy without fluid replacement at the start of surgery.We will combine it with fluid restriction to prevent excessive fluid administration and its effect on splanchnic blood volume and blood loss, combined with the effect of the phlebotomy, as well as to limit fluid overload, as previously reported. Fluid will be administered to compensate blood loss and treat severe hemodynamic instability.The phlebotomy will be transfused back at the beginning of the reperfusion phase where fluid management will be based on a goal-directed therapy (GDT) using either PPV or SV, as in the control group.', 'interventionNames': ['Procedure: Low splanchnic blood volume restrictive fluid management strategy', 'Procedure: Phlebotomy']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Liberal group: Optimized cardiac output liberal fluid management strategy', 'description': 'The control group will receive a liberal intraoperative fluid management strategy optimizing cardiac output throughout the surgery. It will consist of administering 250 mL fluid boluses until SV stops to increase by more than 10% or until PPV is below 12%, a dynamic indicator of fluid responsiveness validated in many surgical populations, including ESLD patients undergoing a LT.This strategy is informed by data from recent clinical trials on benefits of GDT in major surgery, data on strategies used in major surgery, liver resection or LT and our survey on current practice.', 'interventionNames': ['Procedure: Optimized cardiac output liberal fluid management strategy']}], 'interventions': [{'name': 'Low splanchnic blood volume restrictive fluid management strategy', 'type': 'PROCEDURE', 'otherNames': ['Restrictive arm'], 'description': 'Hemodynamic goal-directed restrictive fluid management strategy.', 'armGroupLabels': ['Restrictive group: Low splanchnic blood volume Restrictive fluid management strategy']}, {'name': 'Optimized cardiac output liberal fluid management strategy', 'type': 'PROCEDURE', 'otherNames': ['Liberal arm'], 'description': 'Permissive intraoperative hemodynamic goal-directed fluid management strategy that optimizes cardiac output throughout surgery', 'armGroupLabels': ['Liberal group: Optimized cardiac output liberal fluid management strategy']}, {'name': 'Phlebotomy', 'type': 'PROCEDURE', 'description': 'Retrieval of blood in a blood donation bag performed prior to dissection and transfused back after graft reperfusion', 'armGroupLabels': ['Restrictive group: Low splanchnic blood volume Restrictive fluid management strategy']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'N6G 2V4', 'city': 'London', 'state': 'Ontario', 'status': 'RECRUITING', 'country': 'Canada', 'contacts': [{'name': 'Nelson Javier Gonzalez Valencia, MD', 'role': 'CONTACT', 'email': 'nelson.gonzalezvalencia@lhsc.on.ca', 'phone': '(519) 661-2111'}, {'name': 'Nelson Javier Gonzalez Valencia, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'London Health Sciences Centre', 'geoPoint': {'lat': 42.98339, 'lon': -81.23304}}, {'zip': 'H2X 0C1', 'city': 'Montreal', 'state': 'Quebec', 'status': 'RECRUITING', 'country': 'Canada', 'contacts': [{'name': 'François-Martin Carrier, MD', 'role': 'CONTACT', 'email': 'francois.martin.carrier.med@ssss.gouv.qc.ca', 'phone': '514-890-8000'}, {'name': 'François-Martin Carrier, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}, {'name': 'Michaël Chassé, MD', 'role': 'SUB_INVESTIGATOR'}], 'facility': "Centre Hospitalier de l'Université de Montréal (CHUM)", 'geoPoint': {'lat': 45.50884, 'lon': -73.58781}}, {'zip': 'H4A 3J1', 'city': 'Montreal', 'state': 'Quebec', 'status': 'RECRUITING', 'country': 'Canada', 'contacts': [{'name': 'Stanislas Kandelman, MD', 'role': 'CONTACT', 'email': 'stanislas.kandelman.med@ssss.gouv.qc.ca', 'phone': '(514)934-1934'}, {'name': 'Stanilas Kandelman, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'McGill University Health Centre', 'geoPoint': {'lat': 45.50884, 'lon': -73.58781}}], 'centralContacts': [{'name': 'François-Martin Carrier, MD', 'role': 'CONTACT', 'email': 'francois.martin.carrier.med@ssss.gouv.qc.ca', 'phone': '514-890-8000'}, {'name': 'Martine Lebrasseur, RN', 'role': 'CONTACT', 'email': 'martine.lebrasseur.chum@ssss.gouv.qc.ca', 'phone': '514-890-8000'}], 'overallOfficials': [{'name': 'Francois-Martin Carrier, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Centre hospitalier université de Montréal'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'End-of-grant KT modalities will be used to reach other important stakeholders, researchers and members of the anesthesia and transplantation community: scientific meetings, publication in an open-access journal, and public presentations with patient partners. Knowledge diffusion on potential difficulties of conducting such trials (and solutions) will be transferred to the research community through the Canadian Perioperative Anesthesia Clinical Trial group (PACT), the Canadian Donation and Transplantation Research Program (CDTRP) and the International Liver Transplantation Society (ILTS) meetings.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': "Centre hospitalier de l'Université de Montréal (CHUM)", 'class': 'OTHER'}, 'collaborators': [{'name': 'Canadian Institutes of Health Research (CIHR)', 'class': 'OTHER_GOV'}, {'name': 'Canadian Donation and Transplantation Research Program (CDTRP)', 'class': 'UNKNOWN'}, {'name': 'Canadian Perioperative Anesthesia Clinical Trial (PACT) Group', 'class': 'UNKNOWN'}], 'responsibleParty': {'type': 'SPONSOR'}}}}