Comparison of Topical and Intravenous Tranexamic Acid in Total Hip Arthroplasty

Study Overview
=================
Brief Summary
-----------------
Recently, there has been interest in applying tranexamic acid topically before the closure of surgical wounds in total hip replacement. It has the advantages of ease of application, maximum concentration at the site of bleeding, minimising its systematic absorption and, potentially , decline the risks for systematic side-effects 。

Detailed Description
-----------------
Objectives:To assess the efficacy and safety between the two different applying routes. Patients in this project are randomly divided into three groups , one group is a blank group and the rest two groups receive either the topical or the intravenous form of tranexamic acid during unilateral THA(total hip arthroplasty).The total blood loss(TBL) will be calculated as the primary outcome for efficacy while the events of Deep Vein Thrombosis、Pulmonary Embolism、Acute Myocardial Infarction 、 Acute Kidney Infarction and Cerebral Infarction will be recorded to assess the safety of the tranexamic acid during a six-week follow-up for each patient. All surgery are under general anesthesia, through direct lateral approach with cementless prosthesis. For all patients, the drain tube is clamped and closed completely for 2 hours; then the clamp is fully opened.

Official Title
-----------------
Comparison of Topical and Intravenous Tranexamic Acid on Blood Loss and Transfusion Rates in Total Hip Arthroplasty

Conditions
-----------------
Blood Loss

Intervention / Treatment
-----------------
* Drug: 0.9% sodium chloride
* Drug: tranexamic acid
* Drug: tranexamic acid


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Consented to join in our project. Adult patients (greater than 18 years old) Patients scheduled for primary unilateral hip arthroplasty Patients for Ruijin hospital, Shanghai, China Exclusion Criteria: Patients who refuse to sign the Inform Consent Had an allergy to TXA. long-term bed >=3 weeks. Using anticoagulant drugs within a week. Coagulopathy (preoperative platelet count <150,000/mm3, INR>1.4, prolonged Activated Partial Thromboplastin Time，Prothrombin Time ，or thrombin time (>1.4 times longer than normal) Pregnancy Breastfeeding Major comorbidities: Severe ischemic heart disease(class III and IV of New York Heart Association); sleep apnea syndrome; renal dysfunction ( glomerular filtration rate<60); or hepatic disfunction(glutamic-pyruvic transaminase>80 or glutamic oxalacetic transaminase>80).Retinopathy (disturbances of color vision). History of thromboembolic disease: . Been participating or been participated within a year in another clinical trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group1<br>60 Milliliters（ml）Normal saline (0.9% sodium chloride) will be applied by soaking the hip cavity for at least 3 minutes before wound closure and then sucked away. | Drug: 0.9% sodium chloride<br>* The normal saline solution will be prepared under sterile conditions. In the operation room the sterile bag containing the solution will be given to the scrub nurse. The contents (60 ml) will be emptied in a sterile surgical bowl and the nurse will ask the surgeon to apply the solution before wound closure.The dosage and applying route can also be looked up in doctor's order sheet.<br>* Other names: normal saline;|
| Experimental: Group2<br>two-dose intravenous tranexamic acid will be applied as follow: 10mg/kg of Tranexamic Acid in 100 Milliliters（ml) normal saline (0.9% sodium chloride),the first dose 15' prior to skin incision and the second dose at 180' after the first dosage. | Drug: tranexamic acid<br>* The Tranexamic Acid solution will be prepared under sterile conditions. In the operation room the sterile bag containing the solution will be given to the scrub nurse. The contents (60 ml) will be emptied in a sterile surgical bowl and the nurse will ask the surgeon to apply the solution before wound closure.The dosage and applying route can also be looked up in doctor's order sheet.<br>* Other names: Cyclokapron;|
| Experimental: Group 3<br>3g Tranexamic Acid diluted to 60 Milliliters（ml） with normal saline (0.9% sodium chloride) will be applied by soaking the hip cavity for at least 3 minutes before wound closure and then sucked away. | Drug: tranexamic acid<br>* The Tranexamic Acid solution will be prepared under sterile conditions. In the operation room the sterile bag containing the solution will be given to the circuit nurse and the circuit nurse will ask the anesthetist to apply the solution intravenously before tourniquet deflation. The dosage and applying route can also be looked up in doctor's order sheet. 60 Milliliters（ml） by irrigation for 3 minutes before wound closure.<br>* Other names: Cyclokapron;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Blood Loss（TBL） | Total Blood Loss（TBL） was estimated with equations described by Gross et al. | estimated by an equation at the fifth postoperative day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transfusion rates | Include The number of units of perioperative blood transfusions, both intraoperative and postoperative, over the course of the patient's hospital stay | from the day of surgery to the day of discharge,an expected average of 7 days | 
| Venous thromboembolic event (symptomatic deep vein thrombosis or pulmonary embolism) | Clinically proven symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) | twelve weeks after surgery | 
| other thromboembolic event | Clinically proven Acute Myocardial Infarction 、 acute kidney infarction or cerebral infarction | twelve weeks after surgery | 
| drainage output | The amount of blood collected by a drain attached to the hip is measured 48 hours after surgery | ti will be recorded at the first day and the second day after surgery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
tranexamic acid, blood loss, topical administration, intravenous administration