The Immunomodulatory Effect of Antrifibrinolytic (Tranexamic Acid) in Total Knee Arthroplasty

NCT03795649 | Unknown DMC

• 1 other identifier: EP-12939/18-1
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The administration of the tranexamic acid (TRAXA), an antifibrinolytic, blocks primary fibrinolysis, and thus the haemorrhage, in the early postoperative period. Significant surgical operations, as well as trauma, initiate a similar dynamic homeostatic mechanism between the creation of a clot (primary and secondary haemostasis) and its dissolution (fibrinolysis). Antifibrinolytics have been proven effective in reducing haemorrhage in patients who have undergone significant surgical operations with normal fibrinolysis, with the use of an appropriate surgical technique. A pharmacokinetic study has shown that peak fibrinolytic activity is present for 6 hours after the incision and it persists for 18 hours in total knee and hip arthroplasty. The administration of the tranexamic acid in optional orthopaedic surgery of total hip (THA) and knee (TKA) arthroplasty reduces the postoperative haemorrhage, as well as the number and volume of the postoperative autologous blood. A trauma in the organism triggers the immunologic response. New term has been introduced - the post-traumatic immunosuppression (PTI), characterised by: a change on the immunologic cells (neutrophilia, monocytosis, increased number of mesenchymal stromal cells, reduced expression of HLA-DR on monocytes, reduced function of natural killer (NK) cells, increased lymphocyte apoptosis, a shift in homoeostasis towards the Th2 phenotype facilitated by Treg lymphocytes - CD4+CD25+CD127-); a change in production levels of various cytokines (anti-inflammatory cytokines): IL-10, IL-4; anti- and pro-inflammatory cytokine: IL-6; pro-inflammatory cytokines IL-2, TNF-α, IFN-γ); the activation of the complement system (C5a and C3a via factor VII - tissue factor system, activated by cell damage). Post-traumatic immunosuppression can be made worse by transfusion, haemorrhage, stress, significant surgical operation and immunosuppressive drugs. The research has shown that Treg lymphocytes CD4+CD25+CD127- have an important role in controlling the acquired and innate immunity (comprising 6-8% of all CD4+ lymphocytes). Stopping haemorrhage prevents the occurrence of anaemia, as well as the need for transfusion of blood products, which lead to developing the post-traumatic immunosuppression (PTI).

Conditions

Hemorrhage

Outcome Measures

Primary Outcomes (1)

• The immunomodulation effect of Tranexamic Acid (IM)

  Trial will include approximately 100 patients in total, which will be divided into four groups of 25 patients. The immunomodulation effect is monitored through the analysis of the lymphocyte subpopulation in the peripheral blood through flow cytometry. The result of each lymphocyte subpopulation will be registered as a percentage of all helper cells (CD4+) and all lymphocytes, as well as their absolute number in the peripheral blood. These parameters will be monitored dynamically in the chronological order as shown below: Day 1 - Preoperatively; Day 1 - Postoperatively T1 (IM) K - 6 hrs postoperatively T1 (IM) A - 6 hrs after the first TRAXA dose, and two hours before LMWH T1 (IM) B - 6 hrs postoperatively (after the transfusion of the autologous blood by means of the autotransfusion system); Day 3 - Postoperatively; Day 5 - Postoperatively; Day 7 - Postoperatively; For immunologic testing of each patient's blood 25 ml (5 ml x 5) during 7 days will be sampled.

  two years

Secondary Outcomes (1)

• The effect of the Tranexamic Acid on the primary fibrinolysis (F)

  two years

Study Arms (4)

The control group (Group K)

NO INTERVENTION

The control group (Group K) is comprised of surgical patients who will not receive blood transfusion, and who have contraindications for Tranexamic Acid.

Group A, Tranexamic acid

ACTIVE COMPARATOR

The treatment group (Group A) is comprised of the patients who will receive Tranexamic acid 1g intravenous 15 min. before releasing the pneumatic tourniquet and the repeating dose 3 hours later

Drug: Tranexamic Acid

Group B, autologous transfusion

OTHER

The treatment group (Group B) will be comprised of the patients who in the second selection have one or more contraindications for Tranexamic Acid administration and transfusion of autologous blood will be performed.

Drug: Tranexamic Acid

Group C, alogenous transfusion

OTHER

The treatment group (Group C) contraindications for Tranexamic Acid administration and the transfusion of alogenous blood will be performed in the case of acute haemorrhage followed by patient's hemodynamic instability.

Drug: Tranexamic Acid

Interventions

Tranexamic Acid DRUG

Imunomodulatory effect

Also known as: Medsamic

Group A, Tranexamic acid; Group B, autologous transfusion; Group C, alogenous transfusion

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ASA I/II status
• scheduled for endoprosthetic total knee arthroplasty.
• laboratory results suitable for elective endoprosthetic surgery: blood panel, coagulation, liver enzymes, kidney function parameters, urine sediment;
• patient voluntarily, in accordance with the KBCSM form on the administration of Tranexamic Acid in endoprosthetic total knee arthroplasty, give their consent for its administration.
• signed informed consent for transfusion

You may not qualify if:

• general anaesthesia
• revision arthroplasty
• previous blood transfusions
• known allergic reaction to TRAXA
• presence of an infection and/or acutization of a chronic disease
• existing malignant disease
• autoimmune disease
• hematologic disease
• diabetes
• renal failure
• liver cirrhosis
• chronic anticoagulant therapy
• analgesia by non-steroidal anti-inflammatory drugs
• combined use of the autologous and allogeneic blood postoperatively when the recovery of the autologous blood is insufficient in relation to the haemorrhage.
• known risk of thrombosis or thromboembolic events (thrombogenic valve disease, thrombogenic rhythm disorder, coagulation-hypercoagulation disorder)

Sponsors & Collaborators

• Sisters of Mercy University Hospital: lead
• Clinical Hospital Centre Zagreb: collaborator

Study Sites (1)

Klinički Bolnički Centar Sestre Milosrdnice

Zagreb, 10000, Croatia

RECRUITING

Related Publications (19)

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• Fragkou PC, Torrance HD, Pearse RM, Ackland GL, Prowle JR, Owen HC, Hinds CJ, O'Dwyer MJ. Perioperative blood transfusion is associated with a gene transcription profile characteristic of immunosuppression: a prospective cohort study. Crit Care. 2014 Oct 1;18(5):541. doi: 10.1186/s13054-014-0541-x.

  PMID: 25270110 BACKGROUND

• Blanie A, Bellamy L, Rhayem Y, Flaujac C, Samama CM, Fontenay M, Rosencher N. Duration of postoperative fibrinolysis after total hip or knee replacement: a laboratory follow-up study. Thromb Res. 2013 Jan;131(1):e6-e11. doi: 10.1016/j.thromres.2012.11.006. Epub 2012 Nov 26.

  PMID: 23195143 RESULT

MeSH Terms

Conditions

Hemorrhage

Interventions

Tranexamic Acid

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Renata Letica-Brnadić

  Clinical Hospital Centre "Sisters of Mercy"

  STUDY CHAIR

Central Study Contacts

Renata Letica-Brnadić

CONTACT

+38598340722; rlbrnadic@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 30, 2018
• First Posted: January 8, 2019
• Study Start: December 18, 2018
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: January 8, 2019

Record last verified: 2019-01

Locations

CR (1)