Plasma Concentrations of Intraosseous Versus Intravenous Tranexamic Acid in Joint Arthroplasty

Официальное название

A Prospective Randomized Controlled Trial Comparing Plasma Concentrations of Intraosseous and Intravenous Tranexamic Acid in Patients Undergoing Joint Arthroplasty

Обзор

This prospective randomized controlled trial aims to compare the pharmacokinetic profiles of intraosseous and intravenous tranexamic acid administration in patients undergoing primary total joint arthroplasty. Eligible patients undergoing total hip or total knee arthroplasty will be randomly assigned to receive tranexamic acid either through intraosseous injection or intravenous injection at a dose of 15 mg/kg. Blood samples will be collected at predefined time points to evaluate plasma concentrations and pharmacokinetic characteristics of tranexamic acid. Secondary outcomes include coagulation function, intraoperative blood loss, transfusion rate, and hemoglobin changes. The study aims to provide evidence regarding the pharmacokinetic characteristics and clinical feasibility of intraosseous tranexamic acid administration in joint arthroplasty.

Подробное описание

This study is a prospective randomized controlled trial designed to compare the plasma concentration profiles and pharmacokinetic characteristics of intraosseous and intravenous tranexamic acid administration in patients undergoing primary total joint arthroplasty. Stratified randomization will be used in this study. Participants will first be stratified according to the type of procedure, either total hip arthroplasty (THA) or total knee arthroplasty (TKA). Within each stratum, patients will be randomly assigned in a 1:1 ratio to either the intraosseous administration group or the intravenous administration group using a random number table or a computer generated randomization sequence. This approach ensures a balanced distribution of surgical procedures between the two treatment groups.

A total of 80 patients scheduled for primary total hip arthroplasty or total knee arthroplasty will be enrolled. Sample size calculation was based on an equivalence design with a significance level of 0.05 and a statistical power of 80%. Allowing for an anticipated dropout rate of approximately 10%, 40 patients will be recruited within each surgical stratum (THA and TKA). Within each stratum, participants will be randomly assigned in a 1:1 ratio to either the intraosseous administration group or the intravenous administration group using a computer generated randomization sequence, resulting in 20 patients per treatment group in each stratum.

Eligible participants include patients aged 18 to 80 years with osteoarthritis undergoing primary total hip or total knee arthroplasty and classified as ASA physical status I-III. Key exclusion criteria include coagulation disorders, prior pulmonary embolism, tranexamic acid allergy, severe hepatic or renal dysfunction, anticoagulant use, pregnancy, and body mass index greater than 40 kg/m².

Both groups will receive tranexamic acid at a standardized dose of 15 mg/kg. In the intraosseous group, patients undergoing total knee arthroplasty will receive intraosseous injection into the proximal tibial cancellous bone before tourniquet release, while patients undergoing total hip arthroplasty will receive intraosseous injection into the proximal femoral cancellous bone before skin incision. In the intravenous group, tranexamic acid will be administered intravenously.

Arterial blood samples will be collected at 1 minute, 5 minutes, 10 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 6 hours, and 18 hours after administration for plasma concentration analysis and pharmacokinetic curve construction. Secondary outcomes include coagulation parameters, intraoperative blood loss, transfusion rate, and hemoglobin changes. The study aims to clarify the perioperative pharmacokinetic characteristics and potential clinical value of intraosseous tranexamic acid administration in joint arthroplasty.

Вмешательства

• Препарат Tranexamic Acid
  Tranexamic acid was administered at a dose of 15 mg/kg during joint arthroplasty. Depending on study group assignment, the drug was administered either through peripheral intravenous injection or intraosseous injection into the proximal tibial or proximal femoral cancellous bone using a dedicated intraosseous needle.

Первичные конечные точки

• Plasma Concentration of Tranexamic Acid (μg/mL) [Срок оценки: 1 minute, 5 minutes, 10 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 6 hours, and 18 hours after tranexamic acid administration]

Вторичные конечные точки (3)

• D-dimer (mg/L) [Срок оценки: Preoperatively and within 18 hours postoperatively]
• Fibrinogen(g/L) [Срок оценки: Preoperatively and within 18 hours postoperatively]
• Hemoglobin [Срок оценки: Baseline and 18 hours after surgery]

Критерии участия

Критерии включения

• Age between 18 and 80 years
• Patients scheduled for primary total hip arthroplasty or total knee arthroplasty
• Diagnosis of osteoarthritis
• American Society of Anesthesiologists (ASA) physical status I-III
• Preoperative hemoglobin ≥ 9 g/dL
• Ability to provide written informed consent
• Willingness to comply with postoperative follow up and study procedures

Критерии исключения

• History of coagulation disorders or bleeding disorders
• History of pulmonary embolism
• Known allergy to tranexamic acid
• Pregnancy or breastfeeding
• Severe hepatic or renal dysfunction
• Preoperative anticoagulant therapy
• Body mass index > 40 kg/m²
• Body weight < 45 kg

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• No. 150 Ximen Road — Linhai

Публикации

• Tantavisut S, Artykbay S, Tangwiwat P, Susantitaphong P. Topical tranexamic acid in hip and knee surgery: a meta-analysis of randomized-controlled trials. EFORT Open Rev. 2025 Jul 1;10(7):454-465. doi: 10.1530/EOR-2024-0152. PMID 40591647
• Yoon U, Beausang D, Elia E, Torjman M, Mojica J, Purtill J, Nazarian D, Courtney PM, Kang Y. The effect of tranexamic acid on blood coagulation in primary total hip arthroplasty using rotational thromboelastometry: a randomized controlled trial. EClinicalMedicine. 2025 Jul 21;86:103374. doi: 10.1016/j.eclinm.2025.103374. eCollection 2025 Aug. PMID 40735345
• DeFrancesco CJ, Reichel JF, Gbaje E, Popovic M, Freeman C, Wong M, DeMeo D, Liu J, Gonzalez Della Valle A, Ranawat A, Cross M, Sculco PK, Haskins S, Kim D, Maalouf D, Kirksey M, Jules-Elysee K, Soffin EM, Kumar K, Beathe J, Figgie M, Inglis A Jr, Garvin S, Alexiades M, DelPizzo K, Russell LA, Sideris A, Saleh J, Zhong H, Memtsoudis SG. Effectiveness of oral versus intravenous tranexamic acid in pr PMID 36526484
• Mukasa F, Baba T, Hayashi K, Watari T, Ishijima M. Effects of preoperative systemic administration of tranexamic acid alone on postoperative inflammation and pain in total hip arthroplasty: a retrospective cohort study. Arthroplasty. 2025 Jul 4;7(1):35. doi: 10.1186/s42836-025-00320-3. PMID 40611356
• Jovanovic G, Lukic-Sarkanovic M, Lazetic F, Tubic T, Lendak D, Uvelin A. The Effect of Intravenous Tranexamic Acid on Perioperative Blood Loss, Transfusion Requirements, Verticalization, and Ambulation in Total Knee Arthroplasty: A Randomized Double-Blind Study. Medicina (Kaunas). 2024 Jul 21;60(7):1183. doi: 10.3390/medicina60071183. PMID 39064612
• Wilde JM, Copp SN, Ezzet KA, Rosen AS, Walker RH, McCauley JC, Evans AS, Bugbee WD. No Difference in Blood Loss and Risk of Transfusion Between Patients Treated with One or Two Doses of Intravenous Tranexamic Acid After Simultaneous Bilateral TKA. Clin Orthop Relat Res. 2022 Apr 1;480(4):702-711. doi: 10.1097/CORR.0000000000002037. PMID 35302971
• Bakke HK, Fuskevag OM, Nielsen EW, Dietrichs ES. Intramuscular uptake of tranexamic acid during haemorrhagic shock in a swine model. Scand J Trauma Resusc Emerg Med. 2021 Dec 18;29(1):171. doi: 10.1186/s13049-021-00983-2. PMID 34922577
• Bury G, Fitzpatrick C, Heron B, Cullen W, Scully E, Kachurets K, Zacharchenko L. Ukraine Trauma Project: the feasibility of introducing advanced trauma-care skills to frontline emergency medical services responders. BMJ Open. 2023 Nov 9;13(11):e077895. doi: 10.1136/bmjopen-2023-077895. PMID 37945303

Идентификаторы

NCT: NCT07614087 · K20251218

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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