Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03555383
Other study ID # Semmelweis University
Secondary ID
Status Completed
Phase
First received
Last updated
Start date August 1, 2017
Est. completion date August 31, 2020

Study information

Verified date September 2020
Source Semmelweis University
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

This study evaluates the hemostatic changes defined as hemostasis reserve capacity (HRC) in the first perioperative 48 hours of bloodless liver transplanted patients.


Description:

The liver transplantation is a common lifesaving procedure with an increased risk of bleeding in end stage liver disease patients. Historically liver transplantation (LT) has been associated with major postoperative blood loss, nevertheless in the last couple of years Massicotte had published increasing number of bloodless liver transplantation (LT) based on acute normovolemic hemodilution, portal pressure reduction and "cell saver" technique and Professor Görlinger many publications underlined the targeted, thromboelastometry guided use of factor concentrates in the background of bloodless liver transplantation. The chronic liver disease is associated with a rebalanced and often pro-coagulant hemostasis, a reduced reserve capacity within the system and a potentially considerable risk for a hemostasis imbalance manifested in microvascular bleeding or thrombosis. The maintenance of blood homeostasis basic condition parallel with the replacement of different coagulation factors according to their reduction order during liver transplantation is highlighted in the Professor Görlinger's pyramid of therapy of coagulopathies, which helps to maintain the hemostasis balance in most of all circumstances. The elevated risk of microvascular bleeding is well circumscribed by low coagulation factor levels in many guidelines, at last in the least European Society of Anesthesia guideline of perioperative bleeding management. However, in certain patients would be unfair to treat standard or viscoelastic tests results according to the guidelines in the absence of clinically manifest coagulopathy. The major objective of this study was to investigate the kinetics of hemostasis reserve capacity (HRC) in the perioperative 48 h of blood products less liver transplantation and absence of surgical and non-surgical bleeding by the implementation of the "Görlinger pyramid methodology" on guidelines directive close or slightly lower hemostasis reserves.

Demographic data of the patients, general: Acute Physiology And Chronic Health Evaluation (APACHE II), Sequential Organ Failure Assessment Score (SOFA) and transplantation specific severity scores Donor Risk Index (DRI), Model For End-Stage Liver Disease (MELD) are recorded along with surgical-, cold- and rewarming ischemia times Cold Ischaemic Time (CIT) Warm Ischaemic Time (WIT) or different organ supports. The hemodynamic parameters as intravascular pressure, volume and flow parameters are followed by transpulmonary volumetric hemodynamic technique (PiCCO2 monitor, Maquet). Standardized laboratory assays and hemostatic tests (Factor I-II-V-VII-X-XIII, AT III) are carried out by Sysmex® CS-2000i, Sysmex® XN-1000 and Siemens® Dimension-RXLMAX systems. Intervention required minimal functional hemostasis reserve capacity are defined by triggers as hematocrit: 27%, platelets: 30 G/l, Fibrinogen (FI): 1g/l, Factor II. (FII.), Factor V (FV.), Factor VII (FVII.), Factor X (FX.): 30%, Antithrombin III: 40%, Factor XIII (FXIII.): 60% levels. The estimate blood volume methodology (EBV, blood volume method) is used for to determine the amount of allowable blood loss in volume (ml) that does not require replacement based on current and trigger levels. According to the algorithm, an individualized pyramid of intervention defined as hemostasis reserve capacity are followed at every studied patient. All measurements and calculations are performed before liver transplantation (T1), at arrival on the Intensive Care Unit (T2) and 12-24-48 h after liver transplantation (T3-4-5). The intraoperative whole blood coagulation is noted by thromboelastographic standard kaolin assay (TEG 5000, Haemonetics®) during hepatectomy, anhepatic phase and end of LT.

Data are analyzed with Statistical Package for the Social Sciences (SPSS, version 20.0, SPSS Inc., Chicago, IL) through descriptive statistics (relative frequency distribution, means and ± Standard Deviation (SD) and inferential statistics (Fischer's exact test and r-ANOVA). In all tests, an a priori alpha error p-value of less than 0.05 and confidence intervals (CI) of 95% are considered significant.


Recruitment information / eligibility

Status Completed
Enrollment 59
Est. completion date August 31, 2020
Est. primary completion date August 1, 2020
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria:

- All bloodless liver transplanted patients in Semmelweis University Department of Transplantation and Surgery will be included in the study

Exclusion Criteria:

- Patients with:

Required Red Blood Cells (RBC), Fresh Frozen Plasma (FFP) or platelets replacement in the perioperative first 48 hours, pediatric patients (age < 18 years) and acut liver failure patients.

Study Design


Intervention

Diagnostic Test:
Coagulation factor levels
The minimal functional hemostasis reserve capacity are defined by triggers as hematocrit: 27%, platelets: 30 G/l, Fibrinogen (FI): 1g/l, FII-FV-FVII-FX: 30%, Antithrombin III: 40%, FXIII: 60% levels. The estimate blood volume methodology is used for to determine the amount of allowable blood loss in volume (ml) that does not require replacement based on current and trigger levels. The individualized pyramid of intervention defined as hemostasis reserve capacity are followed at every studied patient. All measurements and calculations are performed before liver transplantation (T1), at arrival on Intensive Care Unit (T2) and 12-24-48 hours after liver transplantation (T3-4-5).

Locations

Country Name City State
Hungary Semmelweis University Budapest Pest Megye

Sponsors (1)

Lead Sponsor Collaborator
Semmelweis University

Country where clinical trial is conducted

Hungary, 

References & Publications (10)

Baron DM, Metnitz PG, Fellinger T, Metnitz B, Rhodes A, Kozek-Langenecker SA. Evaluation of clinical practice in perioperative patient blood management. Br J Anaesth. 2016 Nov;117(5):610-616. — View Citation

Bidlingmaier C, Olivieri M, Hütker S, Dietl S, Kurnik K. Perioperative management of hemostasis in children and adolescents. Blood Cells Mol Dis. 2017 Sep;67:91-95. doi: 10.1016/j.bcmd.2017.01.009. Epub 2017 Jan 16. Review. — View Citation

Gibon E, Courpied JP, Hamadouche M. Total joint replacement and blood loss: what is the best equation? Int Orthop. 2013 Apr;37(4):735-9. doi: 10.1007/s00264-013-1801-0. Epub 2013 Feb 6. Review. — View Citation

Goel R, Cushing MM, Tobian AA. Pediatric Patient Blood Management Programs: Not Just Transfusing Little Adults. Transfus Med Rev. 2016 Oct;30(4):235-41. doi: 10.1016/j.tmrv.2016.07.004. Epub 2016 Aug 1. Review. — View Citation

Görlinger K. [Coagulation management during liver transplantation]. Hamostaseologie. 2006 Aug;26(3 Suppl 1):S64-76. Review. German. — View Citation

Kahvecioglu D, Erdeve O, Alan S, Cakir U, Yildiz D, Atasay B, Arsan S. The impact of evaluating platelet transfusion need by platelet mass index on reducing the unnecessary transfusions in newborns. J Matern Fetal Neonatal Med. 2014 Nov;27(17):1787-9. doi: 10.3109/14767058.2013.879708. Epub 2014 Feb 3. — View Citation

Keir AK, Stanworth SJ. Neonatal Plasma Transfusion: An Evidence-Based Review. Transfus Med Rev. 2016 Oct;30(4):174-82. doi: 10.1016/j.tmrv.2016.07.001. Epub 2016 Jul 9. Review. — View Citation

Kozek-Langenecker SA, Ahmed AB, Afshari A, Albaladejo P, Aldecoa C, Barauskas G, De Robertis E, Faraoni D, Filipescu DC, Fries D, Haas T, Jacob M, Lancé MD, Pitarch JVL, Mallett S, Meier J, Molnar ZL, Rahe-Meyer N, Samama CM, Stensballe J, Van der Linden PJF, Wikkelsø AJ, Wouters P, Wyffels P, Zacharowski K. Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology: First update 2016. Eur J Anaesthesiol. 2017 Jun;34(6):332-395. doi: 10.1097/EJA.0000000000000630. — View Citation

Lang H, Mouracade P, Gimel P, Bernhard JC, Pignot G, Zini L, Crepel M, Rigaud J, Salomon L, Bellec L, Vaessen C, Roupret M, Jung JL, Mourey E, Martin X, Bigot P, Bruyère F, Berger J, Ansieau JP, Salome F, Hubert J, Pfister C, Trifard F, Gigante M, Baumert H, Méjean A, Patard JJ. National prospective study on the use of local haemostatic agents during partial nephrectomy. BJU Int. 2014 May;113(5b):E56-61. doi: 10.1111/bju.12397. Epub 2013 Oct 31. — View Citation

Massicotte L, Denault AY, Thibeault L, Hevesi Z, Nozza A, Roy A. Relationship between conventional coagulation tests and bleeding for 600 consecutive liver transplantations. Transplantation. 2014 Jul 27;98(2):e13-5. doi: 10.1097/TP.0000000000000253. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Change of coagulation factor levels and hemostasis reserve capacity during bloodless liver transplantation from baseline till the second postoperative day Based on coagulation factors measurements the allowable blood loss is calculated and defined as hemostasis reserve capacity till compulsory coagulation factor or blood products replacement is needed to avoid coagulopathic bleeding in the perioperative phase of liver transplantation. The changes of the measured coagulation factors and the hemostasis reserve capacity is counted at the different meaning points: baseline-before liver transplantation (T1), after successful liver transplantation at arrival on intensive care unit-ICU (T2) and postoperatively according to the graft function: 12 hours after liver transplantation (T3), 24 hours after liver transplantation (T4), 48 hours after liver transplantation (T5). Participants will be followed preoperatively, postoperative 0,12, 24, 48. hours after liver transplantation
Secondary Length of Intensive Care Unit stay Participants will be followed for the duration of Intensive Care Unit stay An expected average of 3 days
Secondary Length of hospital stay Participants will be followed for the duration of hospital stay An expected average of 2 weeks
See also
  Status Clinical Trial Phase
Completed NCT02798861 - Controlled Attenuation Parameter (CAP) in Liver Allografts
Completed NCT03527238 - Optimizing Immunosuppression Drug Dosing Via Phenotypic Precision Medicine Phase 2
Completed NCT01696331 - Text Messaging for Adherence in Adolescent Liver Transplant Recipients N/A
Recruiting NCT05051605 - Immune Response to COVID-19 Vaccine in Recipients of Living Donor Liver Transplantation
Recruiting NCT05940857 - Sponsor-Initiated OCS Liver Perfusion (OLP-II) Registry
Completed NCT01598987 - Efficacy, Safety and Tolerability of Everolimus in Combination With Reduced Exposure Cyclosporine or Tacrolimus in Paediatric Liver Transplant Recipients. Phase 3
Active, not recruiting NCT05074160 - OCS Liver Perfusion (OLP) Post-Approval Registry
Completed NCT05087550 - Multicenter Study on Organ Acquisition Costs in the Post Re-Allocation Era: Liver Transplantation
Recruiting NCT04836923 - LIFT Intervention in Liver Transplant Candidates N/A
Not yet recruiting NCT03666689 - Outflow Reconstruction in Right Lobe Living Donor Liver Transplantation
Not yet recruiting NCT06088758 - Normothermic Machine Perfusion of Steatotic Livers for Expansion of Donor Organ Pool N/A
Terminated NCT01230502 - Mycophenolic Acid (MPA) Monotherapy in Liver Transplantation N/A
Completed NCT00171509 - Efficacy and Safety of Cyclosporine Microemulsion Given Once a Day in Adult Stable Liver Transplant Recipients Phase 4
Not yet recruiting NCT06254248 - Safety of Atezolizumab-Bevacizumab in Liver Transplanted Patients With Advanced Hepatocellular Carcinoma Phase 2
Recruiting NCT06075745 - Cytomegalovirus (CMV) Vaccine in Orthotopic Liver Transplant Candidates Phase 2
Completed NCT02057484 - A 5 Year Follow-up of Patients Who Were Previously Enrolled Into an Advagraf Trial Following a Liver or Kidney Transplant
Active, not recruiting NCT03577431 - Liver Transplantation With Tregs at MGH Phase 1/Phase 2
Recruiting NCT06342557 - Transitional ePRO Diary Liver
Not yet recruiting NCT04265157 - Hepato-duodenal Ligament Occlusion and Classic Technique in Liver Transplant
Recruiting NCT02863250 - Australian and New Zealand Massive Transfusion Registry