Clinical trial NCT03897621: The Effect of Tranexamic Acid on Blood Coagulation in Total Hip Arthroplasty Surgery
Official title: The Effect of Tranexamic Acid on Blood Coagulation in Total Hip Arthroplasty Surgery Based on Rotational Thromboelastometry (ROTEM®).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coagulation; Intravascular
Rotational Thromboelastometry
Fibrinolysis; Hemorrhage
Tranexamic Acid
Total Hip Arthroplasty
Keywords: tranexamic acid
Rotational thromboelastometry
Fibrinolysis
viscoelastic essay
Lead sponsor: Thomas Jefferson University
Sponsor class: OTHER
First posted: 2019-04-01
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: double-blinded randomized controlled trial
Primary purpose: TREATMENT

Brief summary: Total hip arthroplasty (THA) is associated with blood loss ranging from 300 to 2000 mL. Tranexamic acid (TXA) is frequently administered prophylactically during this procedure to reduce blood loss by inhibiting fibrinolysis or by stopping naturally occurring clot resolution. TXA is employed currently based on a surgeon's preference. The objective of this study is to quantitate the degree of fibrinolysis using rotational thromboelastometry (ROTEM) and investigate the role of TXA prophylaxis on blood loss in patients undergoing THA in a double-blind fashion. Our hypothesis is that fibrinolysis is minimal at most and TXA prophylaxis is not necessary during THA. All patients, whether they receive TXA or normal saline, will not be at risk, as at this time no data exists to determine which approach is safer or more effective. This is the first study to compare TXA vs. placebo in a double-blinded, randomized controlled trial.

Detailed description: Total hip arthroplasty (THA) is associated with moderate blood loss ranging from 300 to 2000 mL. Tranexamic acid (TXA) is frequently administered prophylactically during this procedure to reduce blood loss by inhibiting fibrinolysis. Most clinical studies reported potential benefit of the treatment demonstrated by less estimated blood loss (EBL), reduced hemoglobin/hematocrit (HH) change, and reduced transfused packed red blood cells (PRBC). However, bleeding complication may be affected more significantly by the degree of surgical trauma and comorbidity of patients than coagulation abnormality. Further, the frequency and severity of fibrinolysis during these procedures have not been well studied. Additionally, TXA administration may increase the tendency of postoperative venous thrombosis by inhibiting fibrinolysis in already prothrombotic patients. The objective of this study is to quantitate the degree of fibrinolysis using rotational thromboelastometry (ROTEM) and investigate the role of TXA prophylaxis on clinical outcome in patients undergoing THA in a double-blind fashion. Our hypothesis is that fibrinolysis is minimal at most and TXA prophylaxis is not necessary during primary THA.

Eligibility criteria: Inclusion Criteria:

* The study population will include total of 200 adults (age range of 18 - 85 years) who are in the American Society of Anesthesiologists (ASA) Physical Status (PS) 1-3. Inclusion criteria are patients undergoing unilateral, primary, total hip arthroplasty.

Exclusion Criteria:

* Exclusion criteria include patient's refusal, patients with history of significant coagulopathy or on anticoagulation therapy. Female patients who are pregnant or nursing will be excluded. In addition, patients with anemia (Hb \< 8 g/dL) or who received blood transfusion within one week before surgery will be excluded. Patient receiving subcutaneous heparin on the same day prior to surgery will be also excluded.

Primary outcomes:
measure: Fibrinolysis
timeFrame: after induction of anesthesia (baseline),
measure: Fibrinolysis
timeFrame: 45 min after drug administration,
measure: Fibrinolysis
timeFrame: one hour after the end of surgery
Secondary outcomes:
measure: Blood loss
timeFrame: during surgery (intraoperative)
measure: blood transfusion
timeFrame: Intraoperative and up to 72-hour after surgery
measure: pre- and postoperative hemoglobin level
timeFrame: up to 72-hour after surgery
measure: Wound infection
timeFrame: up to 72-hour after surgery
measure: Hematoma
timeFrame: up to72-hour after surgery
measure: Thrombotic events (PE, DVT).
timeFrame: up to 72-hour after surgery
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
Study officials:
affiliation: Thomas Jefferson University
name: Uzung Yoon
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wu Y, Yang T, Zeng Y, Si H, Cao F, Shen B. Tranexamic acid reduces blood loss and transfusion requirements in primary simultaneous bilateral total knee arthroplasty: a meta-analysis of randomized controlled trials. Blood Coagul Fibrinolysis. 2017 Oct;28(7):501-508. doi: 10.1097/MBC.0000000000000637.
citation: Prieto HA, Vincent HK, Deen JT, Iams DA, Parvataneni HK. Tranexamic Acid Effectively Reduces Blood Loss and Transfusion Rates during Simultaneous Bilateral Total Knee Arthroplasty. J Knee Surg. 2018 Mar;31(3):270-276. doi: 10.1055/s-0037-1603333. Epub 2017 May 15.
citation: Na HS, Shin HJ, Lee YJ, Kim JH, Koo KH, Do SH. The effect of tranexamic acid on blood coagulation in total hip replacement arthroplasty: rotational thromboelastographic (ROTEM(R)) analysis. Anaesthesia. 2016 Jan;71(1):67-75. doi: 10.1111/anae.13270. Epub 2015 Nov 12.
citation: Watts CD, Houdek MT, Sems SA, Cross WW, Pagnano MW. Tranexamic Acid Safely Reduced Blood Loss in Hemi- and Total Hip Arthroplasty for Acute Femoral Neck Fracture: A Randomized Clinical Trial. J Orthop Trauma. 2017 Jul;31(7):345-351. doi: 10.1097/BOT.0000000000000837.
citation: Zufferey PJ, Lanoiselee J, Chapelle C, Borisov DB, Bien JY, Lambert P, Philippot R, Molliex S, Delavenne X; investigators of the PeriOpeRative Tranexamic acid in hip arthrOplasty (PORTO) Study. Intravenous Tranexamic Acid Bolus plus Infusion Is Not More Effective than a Single Bolus in Primary Hip Arthroplasty: A Randomized Controlled Trial. Anesthesiology. 2017 Sep;127(3):413-422. doi: 10.1097/ALN.0000000000001787.
citation: Toledo P, McCarthy RJ, Hewlett BJ, Fitzgerald PC, Wong CA. The accuracy of blood loss estimation after simulated vaginal delivery. Anesth Analg. 2007 Dec;105(6):1736-40, table of contents. doi: 10.1213/01.ane.0000286233.48111.d8.
citation: Brecher ME, Monk T, Goodnough LT. A standardized method for calculating blood loss. Transfusion. 1997 Oct;37(10):1070-4. doi: 10.1046/j.1537-2995.1997.371098016448.x.
citation: Theusinger OM, Wanner GA, Emmert MY, Billeter A, Eismon J, Seifert B, Simmen HP, Spahn DR, Baulig W. Hyperfibrinolysis diagnosed by rotational thromboelastometry (ROTEM) is associated with higher mortality in patients with severe trauma. Anesth Analg. 2011 Nov;113(5):1003-12. doi: 10.1213/ANE.0b013e31822e183f. Epub 2011 Sep 14.
citation: Ram GG, Suresh P, Vijayaraghavan PV. Surgeons often underestimate the amount of blood loss in replacement surgeries. Chin J Traumatol. 2014;17(4):225-8.
citation: Levrat A, Gros A, Rugeri L, Inaba K, Floccard B, Negrier C, David JS. Evaluation of rotation thrombelastography for the diagnosis of hyperfibrinolysis in trauma patients. Br J Anaesth. 2008 Jun;100(6):792-7. doi: 10.1093/bja/aen083. Epub 2008 Apr 24.