Liver Transplantation Clinical Trial
— PATACOfficial title:
A Randomized Study of Effect of Preimplantation Portal Vein and Hepatic Artery Liver Flushing With Tacrolimus on Ischemia-reperfusion Injury, Allograft Dysfunction and Liver Histology
The purpose of this study is to determine whether the Tacrolimus added to histidine-tryptophan-ketoglutarate (HTK) solution given through intraportal and intraarterial infusion during back-table procedure is capable of reducing the degree of early allograft liver dysfunction, as assessed by postoperative levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), during first 7 postoperative days and by serum and histochemical markers of liver injury and inflammation.
Status | Completed |
Enrollment | 80 |
Est. completion date | July 2014 |
Est. primary completion date | July 2014 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years to 69 Years |
Eligibility |
Inclusion Criteria: - Donor: age 15-65 years macrovesicular steatosis < 40% (macroscopy or biopsy) sodium <165 mmol/l ICU stay and ventilation < 11 days cold ischemia time < 13 hours AST < 200 U/l ALT < 200 U/l bilirubin < 50 µmol/l application of norepinephrine is allowed - Recipient age: 18-69 Exclusion Criteria: Recipient: - live donor liver transplant - reduced and split grafts - multi organ failure |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Caregiver, Outcomes Assessor), Primary Purpose: Prevention
Country | Name | City | State |
---|---|---|---|
Belarus | RSPC for organ and tissue transplantation, Minsk 9th clinic | Minsk |
Lead Sponsor | Collaborator |
---|---|
Republican Scientific and Practical Center for Organ and Tissue Transplantation |
Belarus,
Busuttil RW, Tanaka K. The utility of marginal donors in liver transplantation. Liver Transpl. 2003 Jul;9(7):651-63. Review. — View Citation
Friedman BH, Wolf JH, Wang L, Putt ME, Shaked A, Christie JD, Hancock WW, Olthoff KM. Serum cytokine profiles associated with early allograft dysfunction in patients undergoing liver transplantation. Liver Transpl. 2012 Feb;18(2):166-76. doi: 10.1002/lt.22451. — View Citation
Ilmakunnas M, Tukiainen EM, Rouhiainen A, Rauvala H, Arola J, Nordin A, Mäkisalo H, Höckerstedt K, Isoniemi H. High mobility group box 1 protein as a marker of hepatocellular injury in human liver transplantation. Liver Transpl. 2008 Oct;14(10):1517-25. doi: 10.1002/lt.21573. — View Citation
Kristo I, Wilflingseder J, Kainz A, Marschalek J, Wekerle T, Mühlbacher F, Oberbauer R, Bodingbauer M. Effect of intraportal infusion of tacrolimus on ischaemic reperfusion injury in orthotopic liver transplantation: a randomized controlled trial. Transpl Int. 2011 Sep;24(9):912-9. doi: 10.1111/j.1432-2277.2011.01284.x. Epub 2011 Jun 14. — View Citation
Olthoff KM, Kulik L, Samstein B, Kaminski M, Abecassis M, Emond J, Shaked A, Christie JD. Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl. 2010 Aug;16(8):943-9. doi: 10.1002/lt.22091. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | early allograft dysfunction | Protocol is restricted to liver transplants performed with classic technique with sequential portal-arterial reperfusion. Early allograft dysfunction will be assessed on the basis of highest levels of AST and ALT during 1-7 postoperative days. |
1-7 postoperative days after liver transplant procedure | Yes |
Secondary | ischemic reperfusion injury of the liver allograft | Protocol is restricted to liver transplants performed with classic technique with sequential portal-arterial reperfusion. A wedge resection of small (5x5mm) part of liver segment-III will be sampled at 2 hours after venous reperfusion. Rate of necrosis, inflammation, vascular thrombosis, cluster of differentiation (CD) 68 and High mobility group box 1 protein (HMGB1) staining will be assessed thereafter. |
liver biopsy taken at 2 hours after portal reperfusion | No |
Secondary | inflammatory response to reperfusion | Protocol is restricted to liver transplants performed with classic technique with sequential portal-arterial reperfusion. After unclamping portal vein but before unclamping the inferior vena cava and after venting of first 100 ml of blood a 5 ml sample of blood (code is "HV") from a tube inserted into caval suture line will be taken. Another 5 ml sample of blood (code is "C") will be taken by puncture of one of hepatic veins 20 min later. Samples (5 ml each) of peripheral blood will be taken on 1st and 3d postoperative day (POD). P-selectin, interleukin-6, interleukin-8, tumor necrosis factor alfa (TNF-a) and macrophage inflammatory protein 1 alpha (MIP-1a) will be determined in samples "HV" and "C". Interleukin-8, elastase, TNF-a and vascular endothelial growth factor (VEGF) will be determined in samples of 1st and 3d POD. |
0 and 20 min after portal reperfusion, 1 and 3 postoperative day | No |
Secondary | Postreperfusion hyperfibrinolysis | Protocol is restricted to liver transplants performed with classic technique with sequential portal-arterial reperfusion. Peripheral blood samples will be taken 15 min and 2 hours after portal reperfusion. Hyperfibrinolysis will be diagnosed by Thromboelastometry (ROTEM) if one or more following criteria are met: LI30<85% or ML>15% or LI60<85% or A10 in Extem is by 15% is less then A10 in Aptem. |
15 min and 2 hours after portal reperfusion | Yes |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT04180735 -
Intestinal Perforation in Patients Receiving an Orthtopic Liver Transplantation in the Montpellier University Hospital
|
||
Completed |
NCT01011205 -
Phase 3b Study to Evaluate Advagraf in Combination With Mycophenolate Mofetil and Basiliximab in Liver Transplantation
|
Phase 3 | |
Completed |
NCT01888432 -
Efficacy and Safety of Everolimus in Liver Transplant Recipients of Living Donor Liver Transplants
|
Phase 3 | |
Recruiting |
NCT04203004 -
HOPE With Cytokine Filtration in Liver Transplantation (Cyto-HOPE)
|
N/A | |
Recruiting |
NCT04564313 -
Safety and Efficacy of Camrelizumab (Anti-PD-1 Antibody) in Recurrent HCC After Liver Transplantation
|
Phase 1 | |
Not yet recruiting |
NCT02544906 -
Propofol Versus Dexmedetomidine for Prevention of Sevoflurane Agitation in Recipients of Living Donor Liver Transplantation
|
N/A | |
Withdrawn |
NCT03596970 -
Study of the Effect of Everolimus Immunosuppressive Combination Therapies on Renal Function When Used as a Maintenance Treatment for Liver Transplant Patients.
|
Phase 3 | |
Completed |
NCT03133065 -
Early Treatment of Recurrent HCV- Infection Post Liver Transplantation in the Era of DAAs
|
Phase 4 | |
Recruiting |
NCT01705015 -
Organ Transplantation Rehabilitation: Effect of Bedside Exercise Device and Activity Reinforcement
|
N/A | |
Completed |
NCT01655563 -
Pharmacogenetic Trial of Tacrolimus After Pediatric Transplantation
|
Phase 2 | |
Completed |
NCT01425385 -
Autoregulation Assessment During Liver Transplantation
|
N/A | |
Terminated |
NCT01445236 -
Pilot Study of Immunosuppression Drug Weaning in Liver Recipients Exhibiting Biomarkers of High Likelihood of Tolerance
|
N/A | |
Completed |
NCT00938860 -
Sustained Virological Response (SVR) to Antiviral Treatment of Liver Transplant Recipients With Recurrent Hepatitis C
|
Phase 4 | |
Completed |
NCT00531921 -
Effects of Donor and Recipient Genetic Expression on Heart, Lung, Liver, or Kidney Transplant Survival
|
N/A | |
Withdrawn |
NCT00585429 -
Evaluation of Kidney Disease in Liver Transplant Recipients
|
N/A | |
Terminated |
NCT00585858 -
Cytokine Kinetics Test to Assess the Presence or Absence of Tolerance in Organ Transplant
|
N/A | |
Completed |
NCT00456235 -
Reduction in the Risk of Rejection by Mycophenolate Mofetil Dose Adjustment in Liver Transplant Patients With Side Effects Caused by the Calcineurine Inhibitors
|
Phase 4 | |
Recruiting |
NCT00147459 -
Immunogenicity of Booster Hepatitis B Vaccines in Children After Liver Transplantation
|
N/A | |
Withdrawn |
NCT00167492 -
Enteric Coated Myfortic for Liver Transplant Recipients
|
Phase 4 | |
Terminated |
NCT00161356 -
Ambisome in Liver Transplant Patients
|
Phase 4 |