Tranexamic Acid for Postoperative Pain

Overseen By Gina Panek, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Matthew Grosso, MD

Must not be taking: Neuroleptics, Immune-suppressives

Disqualifiers: Cancer, DVT, Neuropathy, Addiction, others

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: 1

Duration: 3 days

80 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop all current medications. However, you cannot participate if you are currently on neuroleptic agents like gabapentin, pregabalin, or duloxetine, or if you have clinically significant drug interactions. If you are on immune-suppressive medications or chemotherapy, you are also excluded. Chronic opioid use within 4 weeks prior to surgery is not allowed.

What data supports the idea that Tranexamic Acid for Postoperative Pain is an effective drug?

The available research shows that Tranexamic Acid (TXA) is effective in reducing blood loss after knee surgery, which can help with pain management. One study found that patients who received TXA had 340 mL less blood loss on average compared to those who did not receive it. This reduction in blood loss also meant fewer blood transfusions were needed. Another study showed that TXA helped reduce the need for morphine, a pain medication, after surgery. These findings suggest that TXA not only helps with blood loss but also with managing pain after surgery. ^{1 2 3 4 5}

What safety data is available for Tranexamic Acid in treating postoperative pain?

The provided research does not contain safety data for Tranexamic Acid or its other names like Cyklokapron, Lysteda, etc. The studies focus on other drugs such as dextromethorphan and ketorolac for postoperative pain management. ^{6 7 8 9 10}

Is the drug Tranexamic acid a promising treatment for postoperative pain?

The provided research articles do not discuss Tranexamic acid as a treatment for postoperative pain, so we cannot determine if it is promising for this purpose based on the given information. ^{7 11 12 13 14}

What is the purpose of this trial?

The primary purpose of this study is to evaluate postoperative pain. Secondary outcomes evaluated in this study will include range of motion (ROM), opioid consumption, and ambulation. Each outcome measure will be evaluated, oral tranexamic acid (TXA) in the experiment arm and placebo in the control arm, after total knee arthroplasty (TKA) at postoperative days 0-3, and weeks 1, 2, 6, and 12.

Eligibility Criteria

This trial is for individuals who have undergone total knee arthroplasty (TKA) and are experiencing postoperative pain. Participants should be able to take oral medication and follow the study's schedule for evaluations. Specific inclusion or exclusion criteria details were not provided.

Inclusion Criteria

I am having a knee replacement surgery, either by hand or with a robot.

My surgery will be performed by a CJRI surgeon listed in the trial criteria.

I have been diagnosed with knee osteoarthritis.

Exclusion Criteria

I am having or have had a revision of my knee replacement.

Non-English speaking and reading patient populations

I had no major complications during surgery that made my condition worse.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral tranexamic acid or placebo following total knee arthroplasty

3 days

In-hospital stay

Follow-up

Participants are monitored for postoperative pain, range of motion, opioid consumption, and ambulation status

12 weeks

Follow-up visits at weeks 1, 2, 6, and 12

Treatment Details

Interventions

• Tranexamic acid

Trial Overview The study is testing whether taking oral Tranexamic acid (TXA) can reduce pain after knee surgery compared to a placebo. It will also look at how TXA affects range of motion, opioid use, and walking ability during recovery up to 12 weeks post-surgery.

Participant Groups

Group I: TXA Active Control 1 Intervention

- 1.95 grams oral TXA (tranexamic acid) (3- 650 mg tablets) administered postop day one, postop day two and postop day three. Compounded by registered pharmacist and labeled with subject name and instructions for use.

Group II: Placebo Placebo Group 1 Intervention

- 3 tablets administered postop day one, postop day two and postop day three. Compounded by registered pharmacist and labeled with subject name and instructions for use.

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?

Matthew Grosso, MD

Lead Sponsor

Trials

1

Recruited

80+

Findings from Research

In a study of 228 patients undergoing total knee arthroplasty, both intra-articular (IA) and intravenous (IV) administration of tranexamic acid (TXA) significantly reduced perioperative blood loss compared to no TXA, with IA-TXA showing a greater reduction.

The IA-TXA group also experienced significantly lower pain scores and required less morphine for pain management in the first 48 hours post-surgery, suggesting it may be a more effective option for pain control after knee surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intra-Articular Tranexamic Acid Mitigates Blood Loss and Morphine Use After Total Knee Arthroplasty. A Randomized Controlled Trial. Laoruengthana, A., Rattanaprichavej, P., Rasamimongkol, S., et al.[2020]

In a study of 179 total knee arthroplasties, the use of tranexamic acid before tourniquet release significantly reduced postoperative blood loss by an average of 340 mL compared to a control group.

Patients treated with tranexamic acid also experienced a reduction in blood transfusions, going from a median of 2 units in the control group to 0 units, with no significant increase in complications except for a higher number of postoperative hematomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does tranexamic acid reduce blood loss in knee arthroplasty? Benoni, G., Carlsson, A., Petersson, C., et al.[2022]

A meta-analysis of 28 randomized controlled trials involving 4,200 participants found that combined administration of tranexamic acid (TXA) significantly reduces total blood loss and postoperative hemoglobin drop compared to using TXA through a single route (oral, intravenous, or topical).

Oral administration of TXA showed similar efficacy to intravenous or topical routes, indicating that it can be an effective alternative for reducing blood loss in total knee arthroplasty.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What is the ideal route of administration of tranexamic acid in total knee arthroplasty? A meta-analysis based on randomized controlled trials. Lu, F., Sun, X., Wang, W., et al.[2021]

In a study of 63 patients undergoing total knee arthroplasty, both intra-articular (IA) and periarticular (PA) tranexamic acid (TXA) were found to be equally effective in reducing blood loss and improving immediate postoperative pain relief.

There were no significant differences in postoperative outcomes, such as hemoglobin drop, pain scores, or functional recovery, between the IA and PA TXA groups, suggesting that either method can be safely used in this surgical context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local infiltration of analgesia and tranexamic acid is safe and efficacious in reducing blood loss and comparable to intra-articular tranexamic acid in total knee replacements. Sivasubramanian, H., Tan, CMP., Wang, L.[2021]

In a study of 177 total knee arthroplasty patients, pharmacist intervention in managing tranexamic acid (TXA) treatment significantly reduced total blood loss from 1133.31 mL in the control group to 604.34 mL in the intervention group (P < 0.001).

The intervention also decreased the rate of allogeneic blood transfusions from 40.91% in the control group to 21.35% in the intervention group (P = 0.01), demonstrating both clinical efficacy and cost savings without compromising safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of pharmacist intervention on blood conservation therapy in total knee arthroplasty: A retrospective, observational study. Zhou, L., Ma, J., Bao, J.[2019]

In a study of 92 patients, the combination of transdermal fentanyl and intramuscular ketorolac significantly reduced postoperative pain compared to ketorolac alone, with lower pain scores and reduced need for additional ketorolac.

While the combination treatment was more effective, it did have a higher incidence of pruritus (itching) in patients receiving fentanyl, but overall safety profiles were comparable with no significant differences in serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transdermal fentanyl system plus im ketorolac for the treatment of postoperative pain. Reinhart, DJ., Goldberg, ME., Roth, JV., et al.[2013]

This study is evaluating the efficacy of multi-dose dextromethorphan for managing postoperative pain in 160 participants undergoing total knee arthroplasty, focusing on reducing opioid consumption within the first 24 hours after surgery.

Dextromethorphan is highlighted for its strong safety profile and unique pharmacological properties, making it a promising alternative in opioid-sparing pain management strategies following surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blinded, placebo-controlled, randomized study to evaluate the efficacy of perioperative dextromethorphan compared to placebo for the treatment of postoperative pain: a study protocol. Jones, IA., Piple, AS., Yan, PY., et al.[2023]

In a study of 127 patients undergoing major surgery, intranasal ketorolac at a dose of 31.5 mg significantly reduced the need for supplemental morphine compared to placebo and the lower 10 mg dose, indicating its efficacy in managing postoperative pain.

The 31.5 mg dose of ketorolac also resulted in lower rates of pyrexia and tachycardia compared to placebo, suggesting a better safety profile while effectively controlling pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and analgesic efficacy of intranasal ketorolac in patients with postoperative pain. Moodie, JE., Brown, CR., Bisley, EJ., et al.[2013]

A case study of a 31-year-old man revealed that excessive use of ketorolac tromethamine (Acula) after PRK led to corneal ulceration and perforation, necessitating surgical intervention.

The findings highlight the importance of proper patient education regarding the use of topical NSAIDs post-surgery to prevent complications like corneal damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corneal ulceration and perforation with ketorolac tromethamine (Acular) use after PRK. Mian, SI., Gupta, A., Pineda, R.[2019]

Ketorolac tromethamine significantly prolongs bleeding time and inhibits platelet function, but the changes are modest and generally remain within normal limits for healthy individuals, suggesting limited clinical significance.

When combined with low-dose heparin, ketorolac does not interact negatively, but caution is advised in patients with bleeding disorders due to its antiplatelet effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of ketorolac tromethamine on hemostasis. Greer, IA.[2013]

Tranexamic acid (TAMCA) binds to the GABA binding site of GABA(A) receptors in the central nervous system, leading to hyperexcitability and convulsions, which suggests a mechanism of action that disrupts normal inhibitory signaling.

In experiments with rat spinal cord, TAMCA caused dose-dependent hyperexcitability that could be completely reversed by the GABA(A) receptor agonist muscimol, indicating that TAMCA blocks GABA's inhibitory effects, contributing to its excitatory effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid, a widely used antifibrinolytic agent, causes convulsions by a gamma-aminobutyric acid(A) receptor antagonistic effect. Furtmüller, R., Schlag, MG., Berger, M., et al.[2019]

In a study of 153 patients undergoing total knee arthroplasty, the periarticular (PA) injection method resulted in the lowest morphine consumption and significantly less pain at rest and during activity compared to intra-articular (IA) and combined IA+PA methods.

Patients receiving the PA method also demonstrated greater active and passive knee flexion, indicating better functional recovery in the early postoperative period compared to the other analgesic techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the Effect of Intra-Articular, Periarticular, and Combined Injection of Analgesic on Pain Following Total Knee Arthroplasty: A Double-Blinded Randomized Clinical Trial. Mortazavi, SMJ., Vosoughi, F., Yekaninejad, M., et al.[2022]

In a study of 51 patients undergoing total knee arthroplasty (TKA), the dual-acting local anesthetic HTX-011, combined with a multimodal analgesic (MMA) regimen, significantly reduced postoperative pain and opioid consumption compared to previous treatments.

The majority of patients reported mild pain levels, with 39% being discharged without an opioid prescription, indicating that HTX-011 with MMA is both effective and well-tolerated, with no additional safety risks observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HTX-011 in Combination with Multimodal Analgesic Regimen Minimized Severe Pain and Opioid Use after Total Knee Arthroplasty in an Open-Label Study. Lee, GC., Berkowitz, R., Hacker, S., et al.[2023]

In a study of 57 patients undergoing total knee arthroplasty, both intrathecal morphine and periarticular multimodal drug injection provided similar levels of postoperative pain control, indicating that neither method is superior in managing pain after surgery.

However, patients receiving intrathecal morphine experienced significantly more side effects, such as nausea and itching, compared to those who received the multimodal injection, suggesting that the latter may be a safer option with fewer adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is pain after TKA better with periarticular injection or intrathecal morphine? Tammachote, N., Kanitnate, S., Manuwong, S., et al.[2021]

References

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

Intra-Articular Tranexamic Acid Mitigates Blood Loss and Morphine Use After Total Knee Arthroplasty. A Randomized Controlled Trial. [2020]

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

Does tranexamic acid reduce blood loss in knee arthroplasty? [2022]

3. China pubmed.ncbi.nlm.nih.gov

What is the ideal route of administration of tranexamic acid in total knee arthroplasty? A meta-analysis based on randomized controlled trials. [2021]

4. India pubmed.ncbi.nlm.nih.gov

Local infiltration of analgesia and tranexamic acid is safe and efficacious in reducing blood loss and comparable to intra-articular tranexamic acid in total knee replacements. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Effect of pharmacist intervention on blood conservation therapy in total knee arthroplasty: A retrospective, observational study. [2019]

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

Transdermal fentanyl system plus im ketorolac for the treatment of postoperative pain. [2013]

7. England pubmed.ncbi.nlm.nih.gov

A double-blinded, placebo-controlled, randomized study to evaluate the efficacy of perioperative dextromethorphan compared to placebo for the treatment of postoperative pain: a study protocol. [2023]

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

The safety and analgesic efficacy of intranasal ketorolac in patients with postoperative pain. [2013]

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

Corneal ulceration and perforation with ketorolac tromethamine (Acular) use after PRK. [2019]

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

Effects of ketorolac tromethamine on hemostasis. [2013]

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

Tranexamic acid, a widely used antifibrinolytic agent, causes convulsions by a gamma-aminobutyric acid(A) receptor antagonistic effect. [2019]

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

Comparison of the Effect of Intra-Articular, Periarticular, and Combined Injection of Analgesic on Pain Following Total Knee Arthroplasty: A Double-Blinded Randomized Clinical Trial. [2022]

13. Germany pubmed.ncbi.nlm.nih.gov

HTX-011 in Combination with Multimodal Analgesic Regimen Minimized Severe Pain and Opioid Use after Total Knee Arthroplasty in an Open-Label Study. [2023]

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

Is pain after TKA better with periarticular injection or intrathecal morphine? [2021]