TXA (Tranexamic Acid) vs. Amicar (Aminocaproic Acid) in ..., Exercises of Pharmacy

Download TXA (Tranexamic Acid) vs. Amicar (Aminocaproic Acid) in ... and more Exercises Pharmacy in PDF only on Docsity! TXA (Tranexamic Acid) vs. Amicar (Aminocaproic Acid) in Total Knee and Hip Arthroplasty- Effectiveness, Safety, and Cost Analysis NCT02030821 Document date: 2015-01-15 TXA vs. Amicar in TKA- Effectiveness, safety and cost analysis PI: Michael Bolognesi, MD Version Date 1.15.2015 1 Department of Orthopaedic Surgery TXA (Tranexamic Acid) vs. Amicar (Aminocaproic Acid) in Total Knee and Hip Arthroplasty- Effectiveness, Safety, and Cost Analysis Principal Investigators: Michael Bolognesi, MD Sub-Investigator: Samuel S. Wellman, MD; David Attarian, MD; Stuart Grant, MD Research Summary 2. Purpose Minimization of perioperative discomfort and complications, such as increased blood loss and length of hospital stay is a mutual goal amongst both patients and surgeons alike. To our knowledge, there have been no studies in the US and only one small study in Europe comparing the efficacy of tranexamic acid (TXA) and Ƹ- aminocaproic acid (EACA or ACA, Amicar®) in TKA and total hip arthroplasty (THA). A double blind, randomized and placebo controlled trial in Spain involving 127 patients sorted into three different arms found that there was significant reduction of blood transfusions in the TKA and Amicar arms, and also less of a reduction in hemoglobin levels by post-op day 5.1 There were no statistical significance in the 35 patients administered TXA compared to the 32 patients administered EACA, and authors noted that the limited number of patients may have prevented any findings.1 Given the potency of TXA, it may in fact be more efficacious than Amicar, leading to improved patient outcomes. Despite the clinical advantages to using TXA vs. placebo, it is frequently felt to be financially prohibitive. TXA currently costs between $100-200 per each IV dose. A unit of RBC costs between $500-1000 dollars. A recent study comparing the cost of TKAs using TXA vs. those that did not found that although the pharmacy cost increased by $140, the total hospital cost was decreased by about $900 (looking at OR, blood, and total costs associated with admission).2 Amicar is significantly less expensive than TXA, and given its theoretically similar mechanism of action, is used as the agent of choice in many hospitals in the United States. Currently TXA is being used at Duke University for total joint arthroplasty. There are limited data comparing the clinical efficacy and cost effectiveness of the two anti-fibrinolytics. Given the increased potency of TXA, it may be more efficacious and ultimately more cost effective than Amicar. The primary objective of this study is to determine the effectiveness of TXA vs. Amicar by determining the percentage of patients requiring transfusions and blood loss in total joint arthroplasty. A secondary objective is to determine the overall cost of hospitalization when the two different products are used. We hypothesize that that TXA will decrease the transfusion rate in patients as compared to Amicar. We also hypothesize that the overall cost of hospitalization will be less in patients with TXA, despite the increased pharmacy cost. TXA vs. Amicar in TKA- Effectiveness, safety and cost analysis PI: Michael Bolognesi, MD Version Date 1.15.2015 4 Department of Orthopaedic Surgery color blindness, and hypercoagulable state. Females of childbearing age will also have a serum pregnancy test drawn before inclusion in this study. A positive pregnancy will result in exclusion from the study. We aim to recruit 400 subjects, 200 total hip and 200 total knees. Subjects may withdraw at anytime. Post operatively, surgery data will be collected via the electronic medical record. Consent will be signed and witnessed before surgery takes place in clinic. 7. Consent Process The investigator or his/her authorized designee will inform the subject of all aspects pertaining to the subject’s participation in the study during the consent process. The process of obtaining informed consent will be in accordance with all applicable regulatory requirements (Federal Register Vol. 48, No. 17, 1982, pp 8951-2). 8. Subject’s Capacity to Give Legally Effective Consent Each patient aged 18 years or older will consent for him or herself. If the patient is less than 18 years of age they will not be considered for the study. 9. Study Interventions Subjects will be randomly assigned in a 1:1 ratio to either an Amicar or TXA arm which are both standard of care at Duke. Subject’s study participation will end at hospital discharge. 10. Risk/Benefit Assessment Potential Benefits: Despite being off-label, TXA and Amicar are already both being used across various fields, including orthopaedics, for their benefit in reducing blood loss, the need for transfusion, and a drop in hemoglobin during major surgery and have shown to be safe to use.1,14,15 Patients given TXA or Amicar will likely experience decreased blood loss and decreased risk of transfusion and as a result may experience shorter hospital stay, fewer complications and decreased cost. Both are currently used as standard of care in total hip and knee replacements. Potential risks: Although initially there was a fear that TXA or EACA would increase the risk of death and thromboembolic events, current evidence suggests that this increase is not statistically significant.8 TXA is currently used as the standard of care at Duke University Hospital. However, subjects in the TXA arm may experience the following adverse effects including GI disturbances (nausea, vomiting, diarrhea), allergic dermatitis, giddiness, and hypotension. The FDA also lists the risk of serious rare side effects including thromboembolic events (such as deep vein thrombosis, pulmonary embolism, cerebral thrombosis, acute renal cortical necrosis, and central retinal artery and vein obstruction), convulsion, chromatopsia, and visual impairment. TXA vs. Amicar in TKA- Effectiveness, safety and cost analysis PI: Michael Bolognesi, MD Version Date 1.15.2015 5 Department of Orthopaedic Surgery Adverse effects associated with Amicar include edema, headache, malaise, hypersensitivity (anaphylaxis), cardiovascular effects (bradycardia, hypotension, peripheral ischemia, thrombosis), GI disturbances (abdominal pain, diarrhea, nausea, vomiting), hematologic effects (agranulocytosis, coagulation disorder, leukopenia, thrombocytopenia), musculoskeletal effects (CPK increase, muscle weakness, myalgia, myopathy, myositis, rhabdomylolysis), neurologic complications (confusion, convulsions, delirium, dizziness, hallucinations, intracranial hypertension, stroke, and syncope), respiratory effects (dyspnea, nasal congestion, pulmonary embolism), rash, pruritis, tinnitus, decreased vision, watery eyes, and urogenital effects (increased BUN and renal failure). Amicar is less potent than TXA so it may lead to increased blood loss and therefore increased risk of transfusion according to one study.1 Many of the above side effects for both TXA and Amicar have been reported in patients with hemophilia. 11. Costs to the Subject: Subject or their insurance provider will be responsible for all costs related to your medical care, including the drugs used in this study. No direct monetary compensation will be offered for inclusion in the proposed study. 12. Data Analysis & Statistical Considerations Subject characteristics and study results including those outlined above (considered complications or adverse events) will be recorded. 1 The primary endpoint for this study is the percentage of patients requiring transfusions. The secondary endpoint include total blood loss (recorded as estimated blood loss intraoperatively as determined by anesthesia staff, and postoperatively recorded by nurses from the output in drains), change in hemoglobin (preoperative vs. postoperative hemoglobin that is routinely measured before discharge), and the total cost of hospitalization as billed by Duke University (including pharmacy cost, price each night in hospitalization, all other charges incurred during admission). Binary variable results will be compared using chi-square and Fisher’s exact tests (where appropriate). We plan a comparison of continuous variable results using Wilcoxon rank sum and t-tests (where appropriate). We will consider multivariable logistic regression in determination of TXA and Amicar and their correlation with the above listed complications and adverse events. Anesthetic techniques will be recorded for analysis and covariate analysis will be performed at the end of the study. In order to perform a cost analysis, total cost of hospitalization including pharmacy cost, potential transfusion costs, and cost of stay. Based on the one small European study, sample size for finding the difference between two proportions was calculated using a proportion of 0.125 patients given Amicar were transfused (n=32 vs. 0.028 (n=35) given TXA. Using an alpha value of .05 and power of .90 it was determined that there TXA vs. Amicar in TKA- Effectiveness, safety and cost analysis PI: Michael Bolognesi, MD Version Date 1.15.2015 6 Department of Orthopaedic Surgery would need to be 154 patients in each sample size to find a significant difference in independent samples. Our goal of enrolling 400 patients total (200 in each arm) will therefore be appropriate for this study 13. Data & Safety Monitoring The primary investigator will collect data from the subject’s electronic medical record and will extract necessary study data and then transfer this data into a limited access electronic Excel spreadsheet housed on the Duke Orthopaedic share drive. We will have an independent safety reviewer in lieu of a formal DSMB committee to ensure the safety of subjects. Dr. Steve Olson, head of the orthopaedic clinical research unit will be asked to serve in this role. He will review available safety data, including thrombotic complications after 100, 200, and 300 patients are enrolled. During collection, data will be indexed by the subject’s medical record number. After data collection, a case number will be assigned to the data, and the medical record number, name and any dates associated with clinical care (the only identifying data collected) will be stripped from the database. The code linking medical record number to case number will be kept in an Excel spreadsheet with access limited to the primary investigator and his research team. Electronic research records will be stored on a DHTS server in the following limited access folder O:\CLINICAL RESEARCH DATA\JOINT\50108 - Bolo TXA vs. Amicar. Paper research documents will be stored in the PI’s locked research office in a locked cabinet with keys in possession of the CRC. Paper documents will be housed in the PI’s locked research office in a locked cabinet with access limited to his research team and keys in possession of the CRC. When the study is complete, the code linking medical record numbers to case numbers will be destroyed. During data collection and review, protected health information will be available only to the primary investigator and will not be reused or disclosed to any other person or entity, except as required by law, for authorized oversight of the research study. 14. Privacy, Data Storage & Confidentiality All data collection will be performed on a secure PIN station protected by DHT firewalls. Only researchers participating in the study will have access to the data. With the exception of medical records numbers, data collection will not contain patient identifiers as specified in the HIPPA regulations (45CFR164.514(b)(2)(i)). All data will be stored as outlined in the research data security plan (RDSP) included with this submission. Subject identity will be made anonymous after completion of the data accrual and prior to statistical analysis to assure confidentiality. Original signed consent forms and collected data will be kept in subject folders in a locked secure location. References