Assessment of the effect of addition of 24 hours of oral tranexamic acid post-operatively to a single intraoperative intravenous dose of tranexamic acid on calculated blood loss following primary hip and knee arthroplasty (TRAC-24): a study protocol for a randomised controlled trial

Abstract

BackgroundWhile it is has been proven that tranexamic acid (TXA) reduces blood loss in primary total hip and knee arthroplasty (THA and TKA), there is little published evidence on the use of TXA beyond 3 h post-operatively. Most blood loss occurs after wound closure and the primary aim of this study is to determine if the use of oral TXA post-operatively for up to 24 h will reduce calculated blood loss at 48 h beyond an intra-operative intravenous bolus alone following primary THA and TKA. To date, most TXA studies have excluded patients with a history of thromboembolic disease.Methods/designThis is a phase IV, single-centred, open-label, parallel-group, randomised controlled trial. Participants are randomised to one of three groups: group 1, an intravenous (IV) bolus of TXA peri-operatively plus oral TXA post-operatively for 24 h; group 2, an IV bolus of TXA peri-operatively or group 3, standard care (no TXA). Eligible participants, including those with a history of thromboembolic disease, are allocated to these groups with a 2:2:1 allocation ratio. The primary outcome is the indirectly calculated blood loss 48 h after surgery. Researchers and patients are not blinded to the treatment; however, staff processing blood samples are. Originally 1166 participants were required to complete this study, 583 THA and 583 TKA. However, following an interim analysis after 100 THA and 100 TKA participants had been recruited to the study, the data monitoring ethics committee recommended stopping group 3 (standard care).DiscussionTRAC-24 will help to determine whether an extended TXA dosing regimen can further reduce blood loss following primary THA and TKA. By including patients with a history of thromboembolic disease, this study will add to our understanding of the safety profile of TXA in this clinical situation.Trial registrationISRCTN registry, ISRCTN58790500. Registered on 3 June 2016, EudraCT: 2015–002661-36.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-2784-3) contains supplementary material, which is available to authorized users.

First Comparative Study of the Effectiveness of the Use of Tranexamic Acid against ε-Aminocapróic Acid via the Oral Route for the Reduction of Postoperative Bleeding in TKA: A Clinical Trial

“…Exclusion criteria included a history of a thrombotic or embolic event (deep vein thrombosis or pulmonary embolism) 1 year prior to surgery; patients with anemia (<120 g/L for females, <130 g/L for males); a clinical history of coagulopathy; previous surgeries of the knee (except for diagnostic or therapeutic arthroscopies) or fractures of the distal femur or proximal tibia; peripheral vascular disease; current bleeding at any site; immunocompromised from a known medical condition or medical therapy; patients who have received aspirin; platelet antiaggregant or coumadin in the week prior to surgery or nonsteroidal anti-inflammatory drugs 5 days prior to surgery; history of myocardial infarction; arteriopathy or unstable angina in the 12 months prior to surgery; treatment with a coronary stent 1 year prior to surgery; preoperative autologous blood donation; those patients whose preoperative assessment corresponded to ASA IV or the procedure was contraindicated in their preoperative assessment by the Departments of Cardiology; Anesthesiology or Internal Medicine; retinopathy (severe vision field limitation and/or color distortion); participation in another clinical trial during the prior year; revision knee replacement; tumor knee replacement; total bilateral knee replacement; cognitive deficit; patients who met the inclusion criteria but did not wish to participate in the study; patients with a diagnosis of terminal chronic kidney disease or with creatinine serum greater than 1.47 mg/dL in preoperative laboratories; patients who were unable to receive oral intake of the drug; pregnant or lactating patients or who were taking oral contraceptives; lateral corner release; lateral retinacular release; combined extensive deep and superficial medial collateral ligament releases; history of seizures; and hypersensitivity to the active substance or to any of the excipients of the study. 24 We also excluded patients if they declined to receive blood products for any reason. 25 No changes were made in the methodology or in the inclusion criteria of the patients after the beginning of the study.…”

“…As the primary outcome measure, total blood loss is independent of clinician or investigator bias, effectively becoming a blinded outcome measure. 24 The primary outcomes were total blood loss (TBL), hidden blood loss (HBL), and external blood loss (EBL). The secondary outcomes were transfusion rate, hemoglobin (Hb) and hematocrit (Hct) drop, the drain output, the pain referenced by the patient using the VAS along with complications and adverse effects.…”

Effectiveness and safety of tranexamic acid in total joint arthroplasty

“…The use of TXA in TJA has not yet been supported by the National Institute for Health and Care Excellence or British Orthopaedic Association guidelines (Hill et al 2018). This is due to the lack of comprehensive review and analysis of existing literature.…”

“…With the numbers of performed surgeries increasing every year worldwide (Schwartz & Lange 2017), TJA accounts for approximately 9.8% of the transfused red blood cells, making it the leading cause of transfusion in surgical patients (Shortt et al 2009). It has been estimated that on average, 500ml to 1600ml of blood is anticipated to be lost in these operations due to soft tissue dissection, reaming and osteotomy of the long bones (Nadeau et al 2015, Hill et al 2018). In addition, tissue plasminogen activator is highly elevated in the first day of surgery, which promotes increased fibrinolytic activity and therefore contributes to postoperative anaemia (Stoicea et al 2018).…”

“…Majority of patients undergoing TJA suffer from comorbidities, and the resulting blood loss potentiates the risk of developing severe cardiopulmonary complications (Hill et al 2018). As a result of increased blood loss during TJA, a large proportion of patients (approximately 10–32%) need blood transfusion (Stoicea et al 2018).…”