- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT07631689
Effect of Discarding Initial Reperfusion Blood on Hemodynamics, Liver Function, and 30-Day Outcomes in Liver Transplantation
Assessment of the Impact of Discarding the Initial Reperfusion Blood on Early Liver Function, Cardiovascular and Metabolic Changes and on 30-Day Liver and Renal Outcomes. A Prospective Randomized Trial in Liver Transplantation
Hepatic reperfusion during liver transplantation remains a critical phase associated with significant hemodynamic and systemic disturbances, despite advances in surgical and anesthetic management. This phase is characterized by the release of acidotic, hypothermic, and hyperkalemic blood containing metabolic byproducts and inflammatory mediators resulting from ischemia-reperfusion injury.
Clinically, reperfusion is associated with hemodynamic instability, including reductions in cardiac output and arterial pressure, as well as cardiac dysfunction and arrhythmias, often requiring pharmacologic support. These alterations may affect not only immediate intraoperative stability but also short- and long-term outcomes for both the patient and the graft.
The abrupt restoration of blood flow to the transplanted liver leads to the systemic release of accumulated metabolites, reactive oxygen species, and inflammatory mediators, contributing to a systemic inflammatory response that may impact distant organs, including the kidneys and heart.
Several revascularization strategies have been investigated to mitigate reperfusion-related injury: initial reperfusion via the portal vein, initial reperfusion through the hepatic artery, and simultaneous reperfusion through the portal vein and hepatic artery.
A less frequently used and insufficiently studied strategy, not routinely or systematically implemented, involves diverting the initial reperfusion blood from the graft to the surgical field, followed by the restoration of hepatic blood outflow to the systemic circulation.
This study hypothesizes that discarding the initial reperfusion blood via the infrahepatic vena cava will attenuate early hemodynamic, metabolic, and inflammatory changes and reduce postoperative complications compared to conventional reperfusion techniques.
Descripción general del estudio
Estado
Intervención / Tratamiento
Descripción detallada
Hepatic reperfusion during liver transplantation remains a critical phase associated with significant hemodynamic and systemic disturbances, despite advances in surgical and anesthetic management. This phase is characterized by the release of acidotic, hypothermic, and hyperkalemic blood containing metabolic byproducts and inflammatory mediators resulting from ischemia-reperfusion injury.
Clinically, reperfusion is associated with hemodynamic instability, including reductions in cardiac output and arterial pressure, as well as cardiac dysfunction and arrhythmias, often requiring pharmacologic support. These alterations may compromise immediate intraoperative stability and have been associated with adverse short- and long-term outcomes for both the recipient and the graft.
The abrupt restoration of blood flow to the transplanted liver results in the systemic release of accumulated metabolites, reactive oxygen species, and inflammatory mediators, triggering a systemic inflammatory response that may extend beyond the liver and affect distant organs, including the kidneys and heart.
Several revascularization strategies have been investigated to mitigate reperfusion-related injury, including portal vein, hepatic artery, and simultaneous reperfusion approaches. However, none have consistently demonstrated a clear benefit in reducing ischemia-reperfusion injury or improving clinical outcomes. An alternative and less explored strategy involves diverting and discarding the initial reperfusion blood from the graft before restoring venous outflow to the systemic circulation.
Patients listed for liver transplantation at the study center will be systematically screened for eligibility. Written informed consent will be obtained from all eligible participants prior to enrollment, in accordance with institutional ethical standards.
This study is a prospective randomized clinical trial designed to evaluate whether discarding the initial reperfusion blood via the infrahepatic vena cava attenuates early hemodynamic, metabolic, and inflammatory disturbances and improves postoperative outcomes compared with conventional reperfusion techniques.
Tipo de estudio
Inscripción (Estimado)
Fase
- No aplica
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Joel Avancini Rocha Filho, MD, PhD
- Número de teléfono: +55 11 981422500
- Correo electrónico: joel.rocha@hc.fm.usp.br
Copia de seguridad de contactos de estudio
- Nombre: Estela Regina Ramos Figueira, MD, PhD
- Número de teléfono: +55 11 999454871
- Correo electrónico: estela.figueira@hc.fm.usp.br
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
- Adults aged 18 years or older
- Candidates for liver transplantation at Hospital das Clínicas, University of São Paulo Medical School (HCFMUSP)
- Able to provide written informed consent
Exclusion Criteria:
- Inability to provide informed consent
- Previous liver surgery
- Fulminant hepatitis
- Specific liver diseases associated with severe electrolyte disturbances
- End-stage renal disease requiring dialysis
- Combined organ transplantation
- Living donor liver transplantation
- Liver retransplantation
- Highly sensitized patients with limited availability of blood products
- Hematologic diseases
- Portal vein thrombosis involving more than 50% of the lumen
- Portopulmonary hypertension (mean pulmonary artery pressure > 20 mmHg), diagnosed preoperatively or intraoperatively
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Reperfusion Blood Discard
Liver transplantation with discarding of the initial 180 mL of reperfusion blood via the infrahepatic vena cava prior to restoration of hepatic blood outflow to the systemic circulation
|
Discarding of the initial 180 mL of reperfusion blood from the graft via the infrahepatic vena cava during liver transplantation prior to restoration of hepatic venous outflow to systemic circulation.
|
|
Comparador activo: Conventional Reperfusion
Standard liver transplantation without discarding the initial reperfusion blood.
|
Conventional liver transplantation without discarding the initial reperfusion blood.
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Peak alanine aminotransferase (ALT)
Periodo de tiempo: Within 72 hours after transplantation
|
Peak serum ALT level (U/L) as a biomarker of early graft injury following liver transplantation.
|
Within 72 hours after transplantation
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Arterial Pressure
Periodo de tiempo: Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1.
|
Monitoring arterial pressure (systolic, diastolic e medium) Unit of Measure: mmHg.
|
Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1.
|
|
Cardiac Rhythm
Periodo de tiempo: Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1
|
Cardiac rhythm monitoring with electrocardiography in ECG lead 2 and V5
|
Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1
|
|
Cardiac Output
Periodo de tiempo: Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1.
|
Monitoring continuous cardiac output.
Unit of Measure: L/min.
|
Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1.
|
|
Arterial serum potassium levels
Periodo de tiempo: Intraoperative and daily from postoperative day 1 up to day 7.
|
Perioperative changes in arterial potassium levels (Unit of measure: mEq/L).
|
Intraoperative and daily from postoperative day 1 up to day 7.
|
|
Blood coagulation thromboelastometry
Periodo de tiempo: Intraoperative (at the start of surgery, 5 minutes after reperfusion, and at the end of surgery).
|
Assessment of intraoperative coagulation changes using rotational thromboelastometry (ROTEM), including EXTEM and FIBTEM parameters, and activated clotting time (ACT).
|
Intraoperative (at the start of surgery, 5 minutes after reperfusion, and at the end of surgery).
|
|
International normalized ratio (INR)
Periodo de tiempo: Daily up to 72 hours after transplantation.
|
Assessment of graft function using international normalized ratio (INR).
|
Daily up to 72 hours after transplantation.
|
|
Aspartate aminotransferase levels (AST)
Periodo de tiempo: Daily up to 7 days and weekly up to 30 days after transplantation.
|
Assessment of graft injury using serum levels of AST (Unit of measure: U/L).
|
Daily up to 7 days and weekly up to 30 days after transplantation.
|
|
Serum Tumor Necrosis Factor-alpha (TNF-α)
Periodo de tiempo: At the start of surgery, end of surgery, postoperative day 1, and postoperative day 3.
|
Serum levels of inflammatory mediator TNF-α (Unit of measure: pg/mL).
|
At the start of surgery, end of surgery, postoperative day 1, and postoperative day 3.
|
|
Serum B-type natriuretic peptide (BNP)
Periodo de tiempo: At the start of surgery, 30 minutes after reperfusion and postoperative day 1.
|
Assessment of BNP levels as a marker of cardiac hemodynamic stress.
Unit of Measure: pg/mL.
|
At the start of surgery, 30 minutes after reperfusion and postoperative day 1.
|
|
Serum creatinine levels
Periodo de tiempo: Up to 30 days after transplantation.
|
Assessment of serum creatinine levels to evaluate renal function (Unit of measure: mg/dL),
|
Up to 30 days after transplantation.
|
|
Postoperative complications
Periodo de tiempo: Within 30 days after transplantation.
|
Complications graded according to the Clavien-Dindo classification.
|
Within 30 days after transplantation.
|
|
ICU length of stay
Periodo de tiempo: Up to 30 days after transplantation.
|
Days of length of stay in the intensive care unit.
|
Up to 30 days after transplantation.
|
|
Hospital length of stay
Periodo de tiempo: Up to 30 days after transplantation.
|
Total hospital length of stay in days.
|
Up to 30 days after transplantation.
|
|
Arterial serum sodium levels
Periodo de tiempo: Intraoperative and daily from postoperative day 1 up to day 7.
|
Perioperative changes in arterial serum sodium levels (Unit of measure: mEq/L).
|
Intraoperative and daily from postoperative day 1 up to day 7.
|
|
Arterial serum lactate levels
Periodo de tiempo: Intraoperative and daily from postoperative day 1 up to day 7.
|
Perioperative changes in arterial serum lactate levels (Unit of measure mg/dL),
|
Intraoperative and daily from postoperative day 1 up to day 7.
|
|
Arterial serum calcium levels
Periodo de tiempo: Intraoperative and daily from postoperative day 1 up to day 7.
|
Perioperative changes in arterial serum calcium levels (Unit of measure mg/dL),
|
Intraoperative and daily from postoperative day 1 up to day 7.
|
|
Serum glucose levels
Periodo de tiempo: Intraoperative and daily from postoperative day 1 up to day 7.
|
Perioperative changes in serum glucose levels (Unit of measure: mg/dL).
|
Intraoperative and daily from postoperative day 1 up to day 7.
|
|
Arterial serum pH
Periodo de tiempo: Intraoperative and daily from postoperative day 1 up to day 7.
|
Perioperative changes in arterial pH units.
|
Intraoperative and daily from postoperative day 1 up to day 7.
|
|
Arterial serum bicarbonate
Periodo de tiempo: Intraoperative and daily from postoperative day 1 up to day 7.
|
Perioperative changes in arterial serum bicarbonate (Unit of measure mmol/L)
|
Intraoperative and daily from postoperative day 1 up to day 7.
|
|
Factor V activity levels
Periodo de tiempo: Daily up to 72 hours after transplantation .
|
Assessment of graft function using Factor V activity levels measure as percentage.
|
Daily up to 72 hours after transplantation .
|
|
Alkaline phosphatase levels
Periodo de tiempo: Daily up to 7 days and weekly up to 30 days after transplantation.
|
Assessement of graft function using alkaline phosphatase levels (Unit of measure: U/L),
|
Daily up to 7 days and weekly up to 30 days after transplantation.
|
|
Gamma-glutamyl transferase levels
Periodo de tiempo: Daily up to 7 days and weekly up to 30 days after transplantation.
|
Assessment of liver function using serum levels of gamma-glutamyl transferase up to 7 days and weekly up to 30 days after transplantation (Unit of measure: U/L).
|
Daily up to 7 days and weekly up to 30 days after transplantation.
|
|
Serum ammonia levels
Periodo de tiempo: Daily up to 7 days and weekly up to 30 days after transplantation.
|
Assessment of serum ammonia levels to evaluate liver function.(Unit of measure: mcmol/L).
|
Daily up to 7 days and weekly up to 30 days after transplantation.
|
|
Serum urea levels
Periodo de tiempo: Up to 30 days after transplantation.
|
Assessment of serum urea levels to evaluate renal function (Unit of measure: mg/dl),
|
Up to 30 days after transplantation.
|
|
Urine output
Periodo de tiempo: Up to 30 days after transplantation.
|
Assessment of renal function measured by daily urine output.
|
Up to 30 days after transplantation.
|
|
Need for renal replacement therapy
Periodo de tiempo: Up to 30 days after transplantation.
|
Need for renal replacement therapy (hemodialysis or continuous renal replacement therapy).
|
Up to 30 days after transplantation.
|
|
Serum Interleukin-6 (IL-6) levels
Periodo de tiempo: At the start of surgery, end of surgery, postoperative day 1, and postoperative day 3.
|
Serum levels of inflammatory mediator IL-6 (Unit of measure: pg/mL),
|
At the start of surgery, end of surgery, postoperative day 1, and postoperative day 3.
|
|
Serum Tumor Necrosis Factor-alpha (TNF-α) levels
Periodo de tiempo: At the start of surgery, end of surgery, postoperative day 1, and postoperative day 3.
|
Serum levels of inflammatory mediator TNF-α levels.
(Unit of measure: pg/mL)
|
At the start of surgery, end of surgery, postoperative day 1, and postoperative day 3.
|
|
Serum Interleukin-17 (IL-17) levels
Periodo de tiempo: At the start of surgery, end of surgery, postoperative day 1, and postoperative day 3.
|
Serum levels of inflammatory mediator IL-17 (Unit of measure: pg/mL).
|
At the start of surgery, end of surgery, postoperative day 1, and postoperative day 3.
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Joel Avancini Rocha Filho, MD, PhD, Hospital das Clínicas, University of São Paulo Medical School
- Director de estudio: Estela Regina Ramos Figueira, MD, PhD, Hospital das Clínicas, University of São Paulo Medical School
- Director de estudio: Maria Jose Carvalho Carmona, MD, PhD, Hospital das Clínicas, University of São Paulo Medical School
- Director de estudio: Wellington Andraus, MD, PhD, Hospital das Clínicas, University of São Paulo Medical School
- Director de estudio: Rui Carlos Detsch Junior, MD, Hospital das Clínicas, University of São Paulo Medical School
- Director de estudio: Luciana Bertocco Paiva Haddad, MD, PhD, Hospital das Clínicas, University of São Paulo Medical School
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 92854125.8.0000.0068
- 2025/09932-0 (Otro número de subvención/financiamiento: São Paulo Research Foundation (FAPESP))
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
Ensayos clínicos sobre Reperfusion Blood Discard
-
University Hospital, RouenReclutamientoHepatitis B | Hepatitis C | SIDAFrancia
-
Haydarpasa Numune Training and Research HospitalTerminadoDesorden sangrantePavo
-
Smiths Medical, ASD, Inc.Terminado
-
Tokat Gaziosmanpasa UniversityTerminadoDientes primarios | Pulpotomía | Sangrado Pulpal; TinciónPavo
-
Ischemia Care LLCTerminadoAccidente cerebrovascular isquémico | Fibrilación auricular | Accidente cerebrovascular trombótico | Ataques isquémicos transitorios | Accidente cerebrovascular cardioembólico | Accidente cerebrovascular de la arteria basilar | Eventos cerebrovasculares transitoriosEstados Unidos
-
Applied Science & Performance InstituteTerminadoDeficiencia de hierro (sin anemia)Estados Unidos
-
Tan Tock Seng HospitalMayo ClinicDesconocidoSepticemia | Fungemia | Bacteriemia | Infección del torrente sanguíneoSingapur
-
University of California, IrvineNational Heart, Lung, and Blood Institute (NHLBI)TerminadoHipertensión | Adherencia a la medicaciónEstados Unidos
-
University Hospital, Clermont-FerrandCentre Jean PerrinDesconocidoAsincronía Ventricular IzquierdaFrancia
-
University of Maryland, BaltimoreTerminadoDeficiencia de hierro no anémicaEstados Unidos