Clinical Trial Comparing Tranexamic Acid (TXA) With Aquamantys Sealer in Total Knee Arthroplasty (TKA)

Study Overview
=================
Brief Summary
-----------------
The aim of the study is to determine if the use of iv TXA or Aquamantys system improve the postoperative hemoglobin and hematocrit after primary TKA and what is the effect of the simultaneous use of iv TXA and Aquamantys on the postoperative hemoglobin and hematocrit. The assumption is that the combination of iv TXA and Aquamantys system will enable an improvement in the postoperative hemoglobin and hematocrit equal or larger than the improvement generated by the use of Aquamantys system alone.

Detailed Description
-----------------
The study is randomized, placebo controlled. The study population includes patients older than 18 years of age undergoing elective total primary knee replacement under spinal anesthesia. All patients enrolled in the study will undergo TKA performed by the same orthopedic surgeon. Since controversies exist regarding the effect of different types of anesthesia (general anesthesia versus spinal or epidural anesthesia) on intraoperative blood loss, in order to eliminate an important confounding variable we decided to exclusively enroll for our study patients that qualify for and agree with spinal anesthesia to be used as the main anesthetic technique for their TKA. All clinical trial procedures will be performed by personnel blinded to study treatment assignment. Unblinding is only allowed for safety concerns in an emergency situation.The only other exception is represented by the surgeon, who can't be blinded in regards to using Aquamantys system and the bipolar sealer. Once a subject becomes eligible for the trial, the investigator or the designee will access the randomization system. Enrolled subjects will be assigned to one of the 4 groups by block randomization of alternating 4 and 8 and 12 patients per block. The Pharmacy Department will provide the iv placebo or the iv TXA according to the randomization process. This clinical trial will be conducted in accordance to this protocol, Good Clinical Practice and applicable regulatory requirements

Official Title
-----------------
A Randomized, Controlled Clinical Trial Comparing the Use of Intravenous Tranexamic Acid With Aquamantys Bipolar Sealer for Blood Loss Reduction in Primary Total Knee Arthroplasty

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

Intervention / Treatment
-----------------
* Drug: Tranexamic Acid
* Device: Aquamantys System
* Other: Control


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult patients over age of 18 undergoing elective total primary knee arthroplasty under spinal anesthesia. Exclusion Criteria: Previous adverse reaction to tranexamic acid Congenital or acquired coagulation disorders Preoperative platelet count of less than 100,000/microliter or INR> 1.4 History of deep venous thrombosis, pulmonary embolism or cerebrovascular accident Patients with acquired defective color vision Renal insufficiency (Glomerular filtration rate <20 ml/min) Severe liver disease Coronary stents Pregnant patients Main anesthetic other than spinal anesthesia

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

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

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tranexamic Acid<br>TXA will be provided ready-to-use as IV infusion with instructions written by the pharmacy department. The TXA dose will be 20mg/kg to be administered as a bolus over 20 minutes | Drug: Tranexamic Acid<br>* see arm/group descriptions<br>* Other names: Cyklokapron;|
| Active Comparator: Aquamantys System<br>The Aquamantys system will be used as indicated by orthopedic surgeon intraoperative. Local temperatures under 100°C are sufficient to shrink collagen fibers in the walls of blood vessels, effectively sealing the blood vessels. Simultaneous RF power and saline delivery. Power settings from 20-200 watts | Device: Aquamantys System<br>* see arm/group descriptions<br>|
| Active Comparator: TXA plus Aquamantys<br>TXA will be provided ready-to-use as IV infusion with instructions written by the pharmacy department. The TXA dose will be 20mg/kg to be administered as a bolus over 20 minutes. The Aquamantys system will be used as indicated by orthopedic surgeon intraoperative. Local temperatures under 100°C are sufficient to shrink collagen fibers in the walls of blood vessels, effectively sealing the blood vessels. Simultaneous RF power and saline delivery. Power settings from 20-200 watts. | Drug: Tranexamic Acid<br>* see arm/group descriptions<br>* Other names: Cyklokapron;Device: Aquamantys System<br>* see arm/group descriptions<br>|
| Placebo Comparator: Control<br>Saline will be provided ready-to-use as IV infusion with instructions written by the pharmacy department. The saline dose will be administered as a bolus over 20 minutes | Other: Control<br>* Standard Electro-cautery and Saline<br>* Other names: Placebo;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change in Hemoglobin (Hb) From the Day of Surgery | Control group- iv placebo normal saline plus regular electrocautery. iv TXA plus regular electrocautery. iv placebo plus Aquamantys system and regular electrocautery. iv TXA and Aquamantys system and regular electrocautery | day of surgery preoperative time to postoperative day 3 or postoperative day 2 if day 3 data are not recorded for the 4 groups | 
| The Change in Hematocrit (Ht) From the Day of Surgery | Control group- iv placebo normal saline plus regular electrocautery. iv TXA plus regular electrocautery. iv placebo plus Aquamantys system and regular electrocautery. iv TXA and Aquamantys system and regular electrocautery | day of surgery preoperative time to postoperative day 3 or postoperative day 2 if day 3 data are not recorded for the 4 groups | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post Operative Blood Loss | The estimated blood loss was determined with the Gross formula [23]. According to a review article published in 2013, Gross's formula though developed in 1983 is still widely used as reported. The formula which is relatively easy to use is described below: Patient blood volume (PBV) = K (1) x height (m) 3 + K (2) x weight (kg) + K (3) Where K (1) = 0.3669 (male), 0.3561(female); K (2) = 0.03219 (male), 0.03308 (female); And K (3) = 0.6041(male), 0.1833 (female) Estimated blood loss = PBV [Hematocritinitial - Hematocritfinal ] / Hematocritmean Where mean hematocrit is the sum of initial and final hematocrit divided by two. | day of surgery preoperative time to postoperative day 3 or postoperative day 2 if day 3 data are not recorded for the 4 groups | 
| Cost Analysis | Charges per case. | day of surgery preoperative time to postoperative day 3 or postoperative day 2 if day 3 data are not recorded for the 4 groups | 
| Adverse Events | Complications: deep venous thrombosis(DVT) or arterial thrombosis, pulmonary embolism(PE), myocardial infarction (MI), cerebrovascular accident (CVA) | day of surgery preoperative time to postoperative day 3 or postoperative day 2 if day 3 data are not recorded for the 4 groups | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Tranexamic Acid, Blood Loss, Aquamantys System, TKA