A Dose-response Study of Tranexamic Acid in Total Hip Arthroplasty

Study Overview
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Brief Summary
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A single preoperative dose of tranexamic acid (TXA) reduces blood loss and red blood cell transfusion in primary hip arthroplasty. Numerous regimens have been tested, ranging from 10mg/kg up to 3g. However the optimal dose to administer is unknown.

Detailed Description
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This dose-response study is a randomized double blind study with five groups of 30 patients each. Patients will be randomized to placebo, tranexamic acid (TXA) 300 mg, tranexamic acid (TXA) 500 mg, tranexamic acid (TXA) 1000 mg or tranexamic acid (TXA) 3000 mg. In addition a pharmacokinetic/pharmacodynamic study will be performed to identify the contribution of tranexamic acid (TXA) plasma concentration as a predictor of intra and postoperative D-Dimer values.

Official Title
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Dose Study of Tranexamic Acid in Total Hip Replacement to Reduce Post-operative Hemoglobin Loss: A Phase 2 Randomized Double-blind Monocentric Study

Conditions
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Arthropathy of Hip

Intervention / Treatment
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* Drug: Placebo
* Drug: Group 1: perfusion of 300 mg Exacyl
* Drug: Group 2: perfusion of 500 mg Exacyl
* Drug: Group 3: perfusion of 1000 mg Exacyl
* Drug: Group 4: perfusion of 3000 mg Exacyl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient requiring primary hip arthroplasty (less than 3 months) Consent of the patient or a family member or the support person Exclusion Criteria: Contraindication to tranexamic acid Contraindication to apixaban Pregnancy Patient receiving a curative anticoagulating treatment in the preoperative period Bilateral or previous hip arthroplasty Hemorrhagic surgery less than 2 weeks old

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Patient will be included in this group by randomization and they will receive a perfusion of NaCl (sodium chloride 9%; placebo) intravenous over 10 minutes just before surgery. | Drug: Placebo<br>* Patient will receive a perfusion of NaCl (sodium chloride 9%; placebo) intravenous over 10 minutes just before surgery.<br>|
| Experimental: Group 1: perfusion of 300 mg Exacyl<br>Patient will be included in the group 2 by randomization and they will receive a perfusion of 300 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery. | Drug: Group 1: perfusion of 300 mg Exacyl<br>* Patient will receive a perfusion of 300 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.<br>|
| Experimental: Group 2: perfusion of 500 mg Exacyl<br>Patient will be included in the group 2 by randomization and they will receive a perfusion of 500 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery. | Drug: Group 2: perfusion of 500 mg Exacyl<br>* Patient will receive a perfusion of 500 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.<br>|
| Experimental: Group 3: perfusion of 1000 mg Exacyl<br>Patient will be included in the group 3 by randomization and they will receive a perfusion of 1000 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery. | Drug: Group 3: perfusion of 1000 mg Exacyl<br>* Patient will receive a perfusion of 1000 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.<br>|
| Experimental: Group 4: perfusion of 3000 mg Exacyl<br>Patient will be included in the group 4 by randomization and they will receive a perfusion of 3000 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery. | Drug: Group 4: perfusion of 3000 mg Exacyl<br>* Patient will receive a perfusion of 3000 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| haemoglobin decrease in the perioperative period | Percentage of haemoglobin change in the perioperative period. It requires the sampling of haemoglobin before surgery and on the eighth postoperative day. | Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of the concentration of tranexamic acid | For tranexamic acid pharmacokinetics, the outcome measure is the sampling of tranexamic blood concentration. | Day 8 | 
| Evolution of the concentration of D-Dimer | For tranexamic acid pharmacodynamics, the outcome is the sampling of D-Dimer levels. | Day 8 | 
| allogenic red blood cell transfusion | For allogenic red blood cell transfusion, the outcome measure will be the percentage of patients that will receive the transfusion of at least one allogenic red blood cell unit in the perioperative period. | Day 8 | 
| severe anaemia | For severe anaemia (defined as a level of haemoglobin <10 gram by deciliter), the outcome measure will be the percentage of patients that will have at least one value of haemoglobin <10 gram by deciliter in the perioperative period. | Day 8 | 
| incidence of symptomatic thrombotic events and death | For the incidence of symptomatic thrombotic events and death, the outcome measure is a combined criteria of venous events (deep venous thrombosis or pulmonary embolism), arterial events (acute coronary syndrome, stroke or peripheral arterial thrombosis) and death. | Day 8 | 
| occurrence of a seizure | Upon the occurrence of a seizure, the endpoint is a clinical endpoint involving either the observation of a generalized tonic-clonic seizure or a partial seizure or absence with epilepsy confirmed by an electroencephalogram interpreted by a blind neurologist in the patient's inclusion group. | Day 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tranexamic acid (TXA), arthroplasty, hip, Exacyl