Oral vs. Intravenous TXA Study Proposal: TJA
Condition: Blood Loss After Primary Total Joint Arthroplasty; Need for Blood Transfusion After Total Joint Arthroplasty
MeSH terms: Hemorrhage
Study type: Interventional

Summary: 
      Purpose: Examine oral and intravenous Tranexamic Acid (TXA) to determine whether or not the
      different routes of drug administration are equivalent in terms of post-operative reduction
      in hemoglobin, number of transfusions, and post-operative blood loss following TJA surgery.

      Hypothesis: Oral and intravenous TXA are equivalent routes of drug administration.
    

Detailed description: 
      Purpose: Examine oral and intravenous Tranexamic Acid (TXA) to determine whether or not the
      different routes of drug administration are equivalent in terms of post-operative reduction
      in hemoglobin, number of transfusions, and post-operative blood loss following TJA surgery.

      Hypothesis: Oral and intravenous TXA are equivalent routes of drug administration.

      Background/Scientific review:

      Total hip or knee arthroplasty is associated with the risk of moderate to significant blood
      loss. Techniques such as the use of antifibrinolytics or desmopressin, or normovolaemic
      haemodilution have been used to reduce the need for allogeneic blood transfusion. Tranexamic
      acid (TXA) has been used to reduce blood loss and transfusion requirement for total hip and
      knee arthroplasty, with good results. Approximately one-third of patients undergoing total
      joint replacement surgery require one to three units of blood postoperatively. Tranexamic
      acid is a synthetic antifibrinolytic agent that has been successfully used intravenously to
      control bleeding after total joint replacement. The use of TXA has been shown to
      significantly reduce the need for blood products during total joint replacement1-4.

      There are only a few studies directly comparing outcomes following the use of intravenous
      tranexamic acid (IVTA) and oral tranexamic acid (OTA) in arthroplasty surgery. In the
      randomized study by Zohar et al5. OTA (n = 20) was associated with significant allogeneic
      blood sparing com- pared with controls (n = 20), but not when compared with short- and
      long-term IVTA regimens. A recent randomized trial comparing OTA (n = 26) with placebo (n =
      20) reported significant reductions in blood drained at 24 hours, and in the fall of both Hb
      and Hct in the OTA group, without any significant difference in the requirement of
      transfusion6.

      Study Design: Prospective, randomized, single-blinded study

      Treatment Groups:

        1. Intravenous TXA Group - 1 gram IV bolus 10 minutes prior to incision

        2. Oral TXA Group - 3 tablets (1950 mg) oral 2 hours prior to incision

      Demographics/Patient Specifics: Age, Sex, ASA score, Weight, Height, Estimated
      intra-operative blood loss, Intra-operative fluids (crystalloid, colloid), Operative time,
      Hospitalization days, BMI, Pre-operative PT/INR, Pre-operative PTT, Pre-operative platelet
      count

      Outcome Measurements:

        1. Post-operative reduction in Hgb - Measure pre-operative Hgb levels and post-operative
           days 0, 1, 2, and 3 Hgb levels. Among the studies presented, they used different time
           points to determine the reduction in Hgb. They either used the post-operative 12-hour
           Hgb, post-operative day 4 Hgb, or the lowest Hgb during the hospitalization. Because we
           rarely have patients stay until post-operative day 4, we will have to make our measure
           off a different time period. We have patients get discharged as early as post-operative
           day 1, so we'll probably have to use the post-operative day 1 Hgb level. We feel a Hgb
           level difference of >1 g/dL is clinically significant.

        2. Post-operative reduction in Hematocrit - Measure pre-operative and post-operative days
           0, 1, 2, and 3 Hematocrit levels

        3. Number of units transfused

        4. Number of patients transfused

        5. Cost comparison - Cost differences resulted from differences in the blood transfusion
           rate, length of hospital stay, and management of complications as well as from the cost
           of the TXA itself

        6. Complications

             1. DVT or PE

             2. Return to the OR within 30 days

             3. Re-admission within 30 days

             4. Superficial infection

             5. Deep infection

             6. Periprosthetic fracture

             7. Cerebrovascular accident or Transient ischemic attack

             8. Dislocation

      Risks/Benefits

      The use of Tranexamic Acid is a standard of care used everyday in both primary and revision
      surgeries, this includes both oral and intravenous forms of Tranexamic Acid. TXA side effects
      include of nausea, vomiting and/or diarrhea. Gastrointestinal upset could occur with Oral
      tranexamic acid.

      The only risk involved is the potential for breach of confidentiality and/or privacy. Below
      is a description of the procedure for maintaining confidentiality. There is no direct benefit
      to the participants in this study.

      Procedures for Maintaining Confidentiality

      A breach of confidentiality and/or privacy is a risk of this study. To prevent this, all
      collected data will be stored electronically in password-protected files to protect patient
      identity and information. All information will be collected and reviewed by the research team
      only. Data will be maintained on a password-protected computer that will be accessible only
      to the study team. No patient identifiers will be maintained in the database.
    

Intervention name(s): Oral Tranexamic Acid; Intravenous Tranexamic Acid
Intervention type(s): Drug; Drug
Intervention description(s): patients will receive 1950mg of oral prior to surgery to help reduce blood loss during total joint replacement; Patients will receive 1950mg of intravenous Tranexamic Acid prior to total joint arthroplasty and blood loss or need for transfusion within 24 hours post operative
Other intervention name(s): TXA; TXA
Intervention MeSH terms: Tranexamic Acid
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention