Tranexamic Acid for Osteoarthritis

Recruiting in Germantown (>99 mi)

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Campbell Clinic

Must not be taking: Anticoagulants, Hormonal contraception

Disqualifiers: Revision TKA, DVT, Cancer, Seizures, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 10 days

120 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using anticoagulants (except for 81mg aspirin) or combination hormonal contraception.

Is tranexamic acid generally safe for humans?

Tranexamic acid has been studied for safety in various conditions, including heavy menstrual bleeding and surgeries like knee and hip replacements. These studies generally support its safety in humans, although specific side effects and risks can vary depending on the condition and dosage. ^{1 2 3 4 5}

How does the drug Tranexamic Acid differ from other treatments for osteoarthritis?

Tranexamic Acid is unique for osteoarthritis as it is primarily known for its role in reducing bleeding by helping blood to clot, unlike other treatments that focus on pain relief or inflammation control. This novel approach could offer a different mechanism of action compared to traditional therapies like NSAIDs or hyaluronic acid injections. ^{6 7 8 9 10}

What is the purpose of this trial?

The utilization of intraoperative tranexamic acid (TXA), whether administered intravenously or orally, has become a standard practice in total joint arthroplasty (TJA). Multiple studies have demonstrated the positive impact that TXA application has on clinical outcomes, including decreased blood loss and transfusion rates, decreased early swelling and ecchymosis, improved early recovery, and potentially superior long-term outcomes. Its ability to mitigate risk of blood loss made ambulatory total knee arthroplasty (TKA) safer for patients. The safety of intraoperative TXA use has also been documented. Sabbag et al. showed that TXA does not increase the risk of venous thromboembolism (VTE), even in those patients who are deemed high-risk. Multiple routes of TXA administration have been studied with each route demonstrating effectiveness in reducing blood loss. Findings showed that oral TXA is noninferior to intravenous TXA, though the median time to reach a target concentration is longer via the oral route and bioavailability is lower. With the benefits of intraoperative TXA clearly documented in literature, multiple centers investigated the utilization of extended TXA postoperatively in hopes of enhancing patient safety and reducing length of stay and healthcare cost. However, these studies reported conflicting outcomes and mostly focused on estimated blood loss, instead of patient reported outcomes. The purpose of this study is to assess the effectiveness and safety of a varying extended oral TXA regimen during the postoperative period. Further, the investigators aim to determine the optimal duration of the TXA regimen to maximize its impact. The investigators hypothesize that an extended oral TXA regimen is safe and effective in improving clinical outcomes in TKA patients.

Research Team

Christopher Holland, MD, MS

Principal Investigator

Campbell Clinic

Eligibility Criteria

This trial is for patients with osteoarthritis who have undergone total knee arthroplasty. It's designed to see if taking oral Tranexamic acid (TXA) after surgery can help reduce blood loss and improve recovery. Patients must meet certain health criteria to join, but specific inclusion and exclusion details are not provided here.

Inclusion Criteria

Fluent in oral and written English

I am having a knee replacement at Campbell Clinic, with the implant chosen by my surgeon.

I am willing to participate in the study.

Exclusion Criteria

I have had cancer before, but it was not serious or spreading.

I am currently using combined hormonal birth control.

I have a history of seizures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral TXA or placebo for 10 days postoperatively

10 days

Daily administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Visits at 2 weeks, 6 weeks, 12 weeks, and 1 year postoperative

Treatment Details

Interventions

• Tranexamic acid

Trial Overview The study tests the safety and effectiveness of extended postoperative use of oral TXA in patients after knee replacement surgery. Participants will receive either TXA or a placebo, and researchers aim to find the best duration for taking TXA to enhance patient outcomes.

Participant Groups

Group I: 3-day tranexamic acid (TXA) Experimental Treatment 2 Interventions

Patients will receive three 1950 milligram (mg) doses of Oral TXA (three 650mg capsules per dose) from POD 1 to POD 3 and 7 doses of Placebo from POD 4 to POD 10.

Group II: 10-day TXA Experimental Treatment 1 Intervention

Patients will receive ten 1950mg doses of Oral TXA (three 650mg capsules per dose) from POD 1 to POD 10.

Group III: Placebo Placebo Group 1 Intervention

Patients will receive 10 doses of microcrystalline cellulose (3 capsules per dose) from postoperative day (POD) 1 to POD 10.

Tranexamic acid is already approved in United States, European Union, Japan for the following indications:

Approved in United States as Lysteda for:

• Heavy Menstrual Bleeding
• Menstrual Disorders
• Bleeding Disorder
• Factor IX Deficiency
• Hemophilia A
• Melasma

Approved in European Union as Cyklokapron for:

• Heavy Menstrual Bleeding
• Menstrual Disorders
• Bleeding Disorder
• Factor IX Deficiency
• Hemophilia A
• Melasma
• Postpartum hemorrhage

Approved in Japan as Nicolda for:

• Heavy Menstrual Bleeding
• Menstrual Disorders
• Bleeding Disorder
• Factor IX Deficiency
• Hemophilia A
• Melasma
• Postpartum hemorrhage

Who Is Running the Clinical Trial?

Campbell Clinic

Lead Sponsor

Trials

15

Recruited

2,100+

Findings from Research

A high initial dose of 60 mg/kg intravenous tranexamic acid (IV-TXA) significantly reduced peri-operative blood loss and transfusion rates in 132 patients undergoing total knee arthroplasty compared to a lower dose of 20 mg/kg.

Patients receiving the higher dose also experienced lower levels of inflammatory markers and pain in the days following surgery, while maintaining similar coagulation parameters and complication rates as those on the lower dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The antifibrinolytic and anti-inflammatory effects of a high initial-dose tranexamic acid in total knee arthroplasty: a randomized controlled trial. Lei, YT., Xie, JW., Huang, Q., et al.[2021]

In a study of 60 patients undergoing bilateral total knee arthroplasty, intravenous tranexamic acid (TXA) significantly reduced total blood loss and the need for blood transfusions compared to the control group, indicating its efficacy in managing perioperative blood loss.

The use of TXA did not increase the risk of deep vein thrombosis or other thromboembolic events, suggesting it is a safe option for patients undergoing knee surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A PROSPECTIVE RANDOMIZED SELF-CONTROLLED STUDY ON EFFECT OF TRANEXAMIC ACID IN REDUCING BLOOD LOSS IN TOTAL KNEE ARTHROPLASTY]. Huang, Z., Zhang, W., Li, W., et al.[2018]

References

1. Germany pubmed.ncbi.nlm.nih.gov

The antifibrinolytic and anti-inflammatory effects of a high initial-dose tranexamic acid in total knee arthroplasty: a randomized controlled trial. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Safety of tranexamic acid in women with heavy menstrual bleeding: an open-label extension study. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

The optimal regimen, efficacy and safety of tranexamic acid and aminocaproic acid to reduce bleeding for patients after total hip arthroplasty: A systematic review and Bayesian network meta-analysis. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Comparison of Oral and Intravenous Tranexamic Acid for Prevention of Perioperative Blood Loss in Total Knee and Total Hip Arthroplasty. [2019]

5. China pubmed.ncbi.nlm.nih.gov

[A PROSPECTIVE RANDOMIZED SELF-CONTROLLED STUDY ON EFFECT OF TRANEXAMIC ACID IN REDUCING BLOOD LOSS IN TOTAL KNEE ARTHROPLASTY]. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Novel hyaluronic acid-methotrexate conjugates for osteoarthritis treatment. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Diclofenac-Hyaluronate Conjugate (Diclofenac Etalhyaluronate) for Knee Osteoarthritis: A Randomized Phase III Trial in Japan. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

The role of intra-articular hyaluronan (Sinovial) in the treatment of osteoarthritis. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Novel hyaluronic acid-methotrexate conjugate suppresses joint inflammation in the rat knee: efficacy and safety evaluation in two rat arthritis models. [2018]

10. Italy pubmed.ncbi.nlm.nih.gov

A systematic review on the optimum management of the use of methotrexate in rheumatoid arthritis patients in the perioperative period to minimize perioperative morbidity and maintain disease control. [2018]