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Trial record 17 of 419 for:    TRANEXAMIC ACID

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

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ClinicalTrials.gov Identifier: NCT03795649
Recruitment Status : Recruiting
First Posted : January 8, 2019
Last Update Posted : January 8, 2019
Sponsor:
Collaborator:
Clinical Hospital Centre Zagreb
Information provided by (Responsible Party):
Renata Letica-Brnadić, Sisters of Mercy University Hospital

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).


Condition or disease Intervention/treatment Phase
Hemorrhage Drug: Tranexamic Acid Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Immunomodulatory Effect of Antrifibrinolytic (Tranexamic Acid) in Total Knee Arthroplasty
Actual Study Start Date : December 18, 2018
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding

Arm Intervention/treatment
No Intervention: The control group (Group K)
The control group (Group K) is comprised of surgical patients who will not receive blood transfusion, and who have contraindications for Tranexamic Acid.
Active Comparator: Group A, Tranexamic acid
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
Imunomodulatory effect
Other Name: Medsamic

Group B, autologous transfusion
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
Imunomodulatory effect
Other Name: Medsamic

Group C, alogenous transfusion
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
Imunomodulatory effect
Other Name: Medsamic




Primary Outcome Measures :
  1. The immunomodulation effect of Tranexamic Acid (IM) [ Time Frame: two years ]

    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.



Secondary Outcome Measures :
  1. The effect of the Tranexamic Acid on the primary fibrinolysis (F) [ Time Frame: two years ]

    The fibrinolytic activity of plasma will be examined through euglobulin lysis time testing Blood sampling follows the same time intervals of blood sampling for determining Treg lymphocytes. Fibrinolysis is monitored until the third postoperative day.

    In total per patient for analysis of the fibrinolytic activity 15 mL (5 mL x 3) of blood will be sampled during a 3-day period.

    Day 1 - Preoperatively; Day 3 - Postoperatively T1 (F) K - 6 hrs postoperatively T1 (F) A - 6 hrs after the first TRAXA dose, and two hours before LMWH T1 (F) B - 6 hrs postoperatively (after the transfusion of the autologous blood by means of the autotransfusion system); Day 3 - Postoperatively;




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Ages Eligible for Study:   30 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion criteria:

  • 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.

Exclusion Criteria refers to the patients for whom Tranexamic Acid was contraindicated: ----thromboembolic events (IM, CVI, DVT)

  • known risk of thrombosis or thromboembolic events (thrombogenic valve disease, thrombogenic rhythm disorder, coagulation-hypercoagulation disorder)
  • epilepsy
  • patients who use oral contraceptives
  • known retinal arterial or venous occlusions.

To patients who fulfil the participation criteria for the trial in the first selection, and for whom TRAXA is contraindicated in the second selection, blood transfusion will be administered in accordance with the indication.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03795649


Contacts
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Contact: Renata Letica-Brnadić +38598340722 rlbrnadic@gmail.com

Locations
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Croatia
Klinički Bolnički Centar Sestre Milosrdnice Recruiting
Zagreb, Croatia, 10000
Contact: Renata Letica-Brnadić    +38598340722    rlbrnadic@gmail.com   
Sponsors and Collaborators
Sisters of Mercy University Hospital
Clinical Hospital Centre Zagreb
Investigators
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Study Chair: Renata Letica-Brnadić Clinical Hospital Centre "Sisters of Mercy"

Publications of Results:
Other Publications:

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Responsible Party: Renata Letica-Brnadić, Principal Investigator, Sisters of Mercy University Hospital
ClinicalTrials.gov Identifier: NCT03795649     History of Changes
Other Study ID Numbers: EP-12939/18-1
First Posted: January 8, 2019    Key Record Dates
Last Update Posted: January 8, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hemorrhage
Pathologic Processes
Tranexamic Acid
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants