Evaluation of the Pharmacokinetic Profile of Tranexamic Acid, After Injection in a Knee Neo-articulation.

Study Overview
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Brief Summary
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Evaluate the pharmacokinetic profile of tranexamic acid injected intra-articularly with or without adrenaline, in a population of patients undergoing knee replacement.

Detailed Description
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Orthopedic population, especially during a knee surgery, is at risk of significant bleeding and blood transfusion in the perioperative period. Tissue damage is associated with the activation of a cascade of mechanisms, in which the activation of the fibrinolyse plays an important role. This is why anti-fibrinolytic agents are regularly used in this context to reduce the perioperative bleeding and the use of blood transfusions. In the majority of cases, tranexamic acid, an analogue agent of lysine, is administered by an intravenous injection and more recently, by an intra-articular injection. Several questions however remain unanswered. what is the clearance of this substance ? does an intra-articular resorbtion exist, resulting in a plasmatic rate of the substance ? If yes, what is the plasmatic rate ? Is the intra-articular effect of tranexamic acid predominant compared to its systemic effect ? Does the addition of adrenalin increase the effect of the tranexamic acid by acting on its absorption ? The efficacy, safety and better administration route of the tranexamic acid remain unknown when injected intra-articularly. The goal of this study is to realize the first pharmacokinetic study after an intra-articular injection of tranexamic acid, alone of along with adrenalin, in a knee neo-articulation.

Official Title
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Evaluation of the Pharmacokinetic Profile of Tranexamic Acid, After Injection in a Knee Neo-articulation.

Conditions
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Knee Prosthesis

Intervention / Treatment
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* Drug: Tranexamic Acid
* Drug: Adrenalin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: programmed PTG, right or left surgery planned within the CHU Brugmann Hospital (Dr Reynders) ASA I to ASA III Signed informed consent within the patient file Exclusion Criteria: re-do surgery urgent or multiple surgery ASA IV or higher Patients with a BMI superior or equal to 40 Patient is a Jehovah Witness Allergy or contra-indication to tranexamic acid Coagulation troubles, defined as: Platelet count < 80 000/mm3 and/or PTT <70% and/or aPTT >45s and/or Fibrinogen <100mg/dL Preoperatory renal insufficiency defined as Creatinin > 3mg/dL and/or Dialysis patients.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tranexamic acid<br>Study of the pharmacokinetic profile of the plasmatic resorption of tranexamic acid after an intra-articular injection. | Drug: Tranexamic Acid<br> <br> |
| Active Comparator: Tranexamic acid + adrenalin<br>Study of the pharmacokinetic profile of the plasmatic resorption of tranexamic acid after an intra-articular injection of tranexamic acid with adrenalin 1/200 000. | Drug: Tranexamic Acid<br> <br> Drug: Adrenalin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The pharmacokinetic profile of tranexamic acid | Blood sampling will be performed to establish the pharmacokinetic profile of tranexamic acid. T0 will be defined as the injection time of tranexamic acid. The first blood sampling (T1) will be made 5 minutes after, with the garrot still in place. The garrot will then be loosened and the following blood samplings will take place at 1 minute, 5 minute, 15 minutes, 30 minutes, 1h, 2h, 4h, 8h, 12h and 24h after garrot loosening. 1ml of blood will be taken at each blood sampling. The blood will be placed in a tube suited for chemistry analysis (green tube with gel) and sent directly to the laboratory for analysis. | 24h | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Knee diameter | This will be part of the semi-quantitative evaluation of the knee bleeding. The diameter of both knees (the one undergoing surgery and the untouched one) will be measured before and after surgery. | 12h | 
| Net weight of the compresses | This will be part of the semi-quantitative evaluation of the knee bleeding. The net weight of the blood soaked compresses will be measured. | 12h | 
| Size of the blood stain on the band aid | This will be part of the semi-quantitative evaluation of the knee bleeding. The size of the blood stain, defined as the percentage of the circumference of the band aid that is blood stained, will be measured. | 12h | 
| Blood loss | The blood loss will be deduced from the estimated circulating volume and the patient hematocrit level before and 72h after surgery. | 72h | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tranexamic acid, knee prosthesis, pharmacokinetic profile