Clinical trial NCT02056444: Efficacy of Intravenous Versus Topical Tranexamic Acid in Primary Total Hip Arthroplasty
Official title: Tranexamic Acid Comparison in Hip Replacement (TeACH-R) Trial: Comparative Efficacy of Intravenous Versus Topical Tranexamic Acid for Reducing Blood Loss in Elective Primary Total Hip Arthroplasty.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Osteoarthritis
Keywords: Blood conservation
Tranexamic acid
Total hip arthroplasty
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: University of Western Ontario, Canada
First posted: 2014-02-06
Enrollment: 149
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Bleeding during and after total hip replacement surgery is a primary concern to the surgical and anaesthetic team. Tranexamic acid is a commonly-used drug that helps blood clotting and decreases surgical bleeding. The investigators commonly administer the drug intravenously prior to the procedure. Some patients are unable to receive the drug in this form, because of risks related to blood clotting. The investigators know, from studies in total knee replacement surgery, that the investigators can deliver tranexamic acid directly to the surgical site (topically), with similar benefits and less of the drug absorbed into the bloodstream, resulting in less risk to the patient. The investigators seek to find if similar benefit in terms of reducing blood loss is seen using topical tranexamic acid in hip replacement surgery. The investigators' hypothesis is that the topical form will be equivalent, but not better than the intravenous form for reducing intra- and postoperative bleeding. The investigators also expect to see decreased levels of tranexamic acid in the bloodstream when it is administered topically.

Detailed description: The study randomizes to 2 separate treatment arms: IV administration of tranexamic acid (TXA) at skin incision and topical administration at time of arthrotomy closure. Sample size calculations indicate that 72 study participants in each group would allow for the study sufficient power to detect a clinically relevant change in post-operative hemoglobin levels, in a non-inferiority study design. A double-blind protocol will be implemented, with consent for study participation obtained at the time of the Pre-Admission Clinic appointment.

Randomization will occur as follows: A sealed envelope, appended to the patient chart at the time of the pre-admission clinic appointment, will be provided to the physician at the time of perioperative blood conservation program review. This physician will open the envelope after ensuring that the patient is a candidate to receive TXA. The order will then be placed for either the topical or intravenous form to be sent with the patient to the operating theatre on the day of surgery. The treating surgeon, anaesthesia team, residents and nurses that are in the operating room on the day of surgery will be away of the study participant's randomization, but have been instructed to avoid discussing the administration group to maintain blinding of the patient as best as possible. During the procedure, either the anaesthetist will administer the IV TXA prior to skin incision, or the surgeon will infiltrate, into the surgical wound, the topical TXA at the time of arthrotomy closure. No team members in the operating theatre will be involved in data collection during the post-operative period, and will be instructed not to disseminate any information regarding the route of administration in the electronic or paper chart. Data will then be collected by an independent reviewer not involved in the randomization process, or the procedure itself. In this fashion, the data collectors as well as the participants will be blinded to the intervention. In the immediate postoperative period, the surgical team will be responsible for making clinical decisions, without any influence of the research team. Best efforts will be made to keep the patient unaware of the results of randomization during their in-hospital stay and at the time of any subsequent follow-up visits.

For the intravenous TXA group, administration will follow the current protocol at London Health Sciences Centre (LHSC), where a standard dose of 20 mg/kg will be given to the patient prior to skin incision. For the topical group, a standard dose of 1.5 grams will be given as per the best current evidence in total knee arthroplasty. The latter will be administered at the end of the procedure; the solution will bathe the operative field for 5 minutes during arthrotomy closure, with the final prosthetic components in situ.

Primary outcome measures include differences in postoperative hemoglobin levels and blood transfusion requirements. The investigators routinely measure hemoglobin levels on post-operative days 1 and 2; subsequent measurements are based on suspicion of continued bleeding. Comparison of these levels will be made with levels obtained in the Pre-Admission Clinic appointment to obtain the delta hemoglobin level (delta-Hgb). The lowest measured value during the patient's stay in hospital will be taken as the determinate value. Secondary outcome measures include the number of units of packed red blood cells (pRBC) transfused, as well as the complication rate, both for transfusion-related and procedure-related complications. Packed RBC transfusion as per Health Canada-recommended Clinical Practice Guidelines, at the discretion of the treating surgical team.

The investigators will also measure plasma levels of tranexamic acid intraoperatively, or in the immediate post-operative period, in order to compare the systemic absorption levels with each route of administration. A 5 mL blood sample will be drawn 1 hour after administration. For the intravenous group, this will occur intraoperatively; for the topical route, this will be drawn in PACU. Precise timing of administration and blood sample collection will be marked on the Chart Abstraction Form. 5 mL of blood will be required for this purpose. The specimen will then be sent to to the core laboratory to be cooled and stored until time of centrifugation. Once centrifuged, serum samples will be frozen at -80 degrees Celsius (-80C). Batches of 20 samples will then be sent to St. Michael's Hospital in Toronto, Ontario, for Tandem Mass Spectrometry. This is the only current available method of analysis for serum TEA levels. All 120 participants in this study will have blood levels of TEA measured in this fashion.

Eligibility criteria: Inclusion Criteria:

* Primary elective total hip arthroplasty
* Cementless total hip implant system
* Candidate for administration of TEA (as per the LHSC Perioperative Blood Conservation Program Medical Directive titled Preoperative Written Order for Tranexamic Acid in Orthopaedic Surgery)
* Fitness for surgery confirmed after Pre-Admission Clinic appointment
* Consent for transfusion of blood or blood-related products obtained at time of Pre-Admission Clinic appointment.
* Ability to read and understand the English language

Exclusion Criteria:

* Not deemed medically fit for major orthopaedic surgery
* Revision total hip arthroplasty
* Non-elective indication for total hip arthroplasty
* History of thrombotic vascular event (VTE) in the previous 12 months, or requiring lifelong anticoagulation related to previous VTE. VTE is defined as cerebrovascular event (stroke, transient ischemic attack), deep vein thrombosis, and pulmonary embolism
* Consent for transfusion of blood or blood-related products not obtained
* History of developmental hip dysplasia in the operative hip
* History of Legg-Calve-Perthes disease in the operative hip
* Documented allergy to TEA, or to any of its constituent agents
* Unable to participate in scheduled follow-up appointments.

Primary outcomes:
measure: Delta-hemoglobin (ΔHgb)
timeFrame: POD0 to day of discharge (estimated time in hospital 2 to 5 days postop after primary THA)
measure: Calculated blood loss
timeFrame: POD0 to day of discharge (estimated time in hospital 2 to 5 days postop after primary THA)
Secondary outcomes:
measure: Venous thromboembolic event (symptomatic deep vein thrombosis or pulmonary embolism)
timeFrame: POD0 to day of discharge (estimated time in hospital 2 to 5 days postop after primary THA); 2 week follow-up; 6 week follow-up; 3 month follow-up.
measure: Acute coronary syndrome
timeFrame: POD0 to day of discharge (estimated time in hospital 2 to 5 days postop after primary THA); 2 week follow-up; 6 week follow-up; 3 month follow-up.
measure: Cerebrovascular accident (stroke)
timeFrame: POD0 to day of discharge (estimated time in hospital 2 to 5 days postop after primary THA); 2 week follow-up; 6 week follow-up; 3 month follow-up.
measure: Acute kidney injury (AKI)
timeFrame: POD0 to day of discharge (estimated time in hospital 2 to 5 days postop after primary THA); 2 week follow-up; 6 week follow-up; 3 month follow-up.
measure: Pneumonia
timeFrame: POD0 to day of discharge (estimated time in hospital 2 to 5 days postop after primary THA); 2 week follow-up; 6 week follow-up; 3 month follow-up.
measure: Other systemic illness/infection
timeFrame: POD0 to day of discharge (estimated time in hospital 2 to 5 days postop after primary THA); 2 week follow-up; 6 week follow-up; 3 month follow-up.
measure: Number of units of packed red blood cell transfused
timeFrame: POD0 to day of discharge (estimated time in hospital 2 to 5 days postop after primary THA)
measure: Hematoma
timeFrame: POD0 to day of discharge (estimated time in hospital 2 to 5 days postop after primary THA); 2 week follow-up; 6 week follow-up; 3 month follow-up.
measure: Length of stay in hospital (days)
timeFrame: POD0 to day of discharge (estimated time in hospital 2 to 5 days postop after primary THA)
measure: Systemic serum tranexamic acid (TXA) levels
timeFrame: One hour after administration of TXA
Other outcomes:
Locations:
city: London
country: Canada
facility: London Health Sciences Centre, University Hospital
state: Ontario
Study officials:
affiliation: The Joint Replacement Institute at London Health Sciences Centre, University Hospital
name: Douglas DR Naudie, MD, FRCSC
role: PRINCIPAL_INVESTIGATOR
affiliation: The Joint Replacement Institute at London Health Sciences Centre, University Hospital
name: James L Howard, MD, MSc, FRCSC
role: PRINCIPAL_INVESTIGATOR
affiliation: Western University and London Health Sciences Centre
name: Richard P Nadeau, BMSc, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ralley FE, Berta D, Binns V, Howard J, Naudie DD. One intraoperative dose of tranexamic Acid for patients having primary hip or knee arthroplasty. Clin Orthop Relat Res. 2010 Jul;468(7):1905-11. doi: 10.1007/s11999-009-1217-8. Epub 2010 Jan 9.
citation: Alshryda S, Mason J, Sarda P, Nargol A, Cooke N, Ahmad H, Tang S, Logishetty R, Vaghela M, McPartlin L, Hungin AP. Topical (intra-articular) tranexamic acid reduces blood loss and transfusion rates following total hip replacement: a randomized controlled trial (TRANX-H). J Bone Joint Surg Am. 2013 Nov 6;95(21):1969-74. doi: 10.2106/JBJS.L.00908.
citation: Imai N, Dohmae Y, Suda K, Miyasaka D, Ito T, Endo N. Tranexamic acid for reduction of blood loss during total hip arthroplasty. J Arthroplasty. 2012 Dec;27(10):1838-43. doi: 10.1016/j.arth.2012.04.024. Epub 2012 Jun 14.
citation: Konig G, Hamlin BR, Waters JH. Topical tranexamic acid reduces blood loss and transfusion rates in total hip and total knee arthroplasty. J Arthroplasty. 2013 Oct;28(9):1473-6. doi: 10.1016/j.arth.2013.06.011. Epub 2013 Jul 23.