Tranexamic Acid for Hemorrhage

Overseen By Kristen A Ban, MD MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Kristen Ban

Disqualifiers: Dialysis, Pregnancy, Thromboembolism, DIC, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

394 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this prospective pragmatic randomized clinical trial is to determine if preoperative administration of tranexamic acid (TXA) reduces bleeding during and after major colorectal surgery. The primary questions are: * Does TXA reduce bleeding during and after surgery (change in hemoglobin from before surgery to lowest value after surgery within 30 days) * Does TXA reduce bleeding complications within 30 days of surgery (blood transfusion, return to the operating room or procedural intervention for bleeding, death due to bleeding) * Does TXA increase the risk of thromboembolic complications within 30 days of surgery (cerebrovascular accident, myocardial infarction, deep venous thrombosis, pulmonary embolism) Researchers will compare preoperative TXA to no TXA to answer the above questions. Participants who receive TXA will receive 1 g TXA IV at the beginning and end of surgery in the operating room.

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

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Tranexamic Acid for hemorrhage?

Tranexamic Acid (TXA) has been shown to significantly reduce mortality in patients who are bleeding following trauma when given quickly, and it is also being tested for improving outcomes in cases of spontaneous brain bleeding. Additionally, TXA is used to control bleeding in various medical situations, such as dental procedures and uterine bleeding. ^{1 2 3 4 5}

Is tranexamic acid (TXA) generally safe for humans?

Tranexamic acid (TXA) is generally considered safe for humans, but there are some risks. It does not increase the risk of blood clots in most cases, but there is a higher risk of blood clots in patients with gastrointestinal bleeding and a risk of seizures with higher doses. ^{6 7 8 9 10}

How is the drug Tranexamic Acid unique in treating hemorrhage?

Tranexamic Acid (TXA) is unique because it works by preventing the breakdown of fibrin, which helps stabilize blood clots and reduce bleeding. Unlike some other treatments, it is used in various situations like trauma, surgery, and heavy menstrual bleeding, and can be administered before reaching the hospital to improve survival in trauma patients. ^{4 11 12 13 14}

Research Team

Kristen A Ban, MD MS

Principal Investigator

The Cleveland Clinic

Eligibility Criteria

This trial is for patients scheduled for major colorectal surgery who are at risk of bleeding. They should not have a history of blood clots, pulmonary hypertension, or be allergic to Tranexamic Acid (TXA). Participants must be willing to potentially receive TXA before their operation.

Inclusion Criteria

I am scheduled for or have had abdominal or pelvic surgery for colorectal issues.

Exclusion Criteria

My kidney function is low, with a creatinine clearance under 30 mL/min.

Known defective color vision (color blind)

I am on long-term dialysis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Treatment

Participants receive 1 g TXA IV at the beginning and end of surgery in the operating room

1 day

1 visit (in-person)

Postoperative Monitoring

Participants are monitored for changes in hemoglobin and bleeding complications within 30 days of surgery

30 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Treatment Details

Interventions

• Tranexamic Acid

Trial Overview The study tests if giving patients Tranexamic Acid (TXA) before colorectal surgery can reduce bleeding during and after the procedure. It also looks at whether TXA lowers the need for blood transfusions or additional surgeries due to bleeding, without increasing the risk of blood clots.

Participant Groups

Group I: Tranexamic Acid Experimental Treatment 1 Intervention

TXA administered as a 1 gram IV bolus in 100ml of normal saline administered over 10 minutes at the start and end of the surgery for a total of 2 grams TXA

Group II: Control (no tranexamic acid) Active Control 1 Intervention

Standard of care

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

Approved in United States as Tranexamic Acid for:

• Heavy menstrual bleeding
• Prevention of excessive bleeding during surgeries

Approved in European Union as Tranexamic Acid for:

• Heavy menstrual bleeding
• Prevention of excessive bleeding during surgeries
• Hereditary angioedema

Approved in Canada as Tranexamic Acid for:

• Heavy menstrual bleeding
• Prevention of excessive bleeding during surgeries

Approved in Japan as Tranexamic Acid for:

• Heavy menstrual bleeding
• Prevention of excessive bleeding during surgeries

Who Is Running the Clinical Trial?

Kristen Ban

Lead Sponsor

Trials

1

Recruited

390+

Findings from Research

Tranexamic acid (TXA) was successfully used to achieve hemostasis in a 72-year-old male patient on rivaroxaban, who experienced persistent bleeding after a biopsy, demonstrating its potential effectiveness in patients on direct oral anticoagulants (DOACs).

The intervention was simple, cost-effective, and required minimal resources, providing a novel approach to manage uncontrollable bleeding in anticoagulated patients when traditional methods were ineffective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical Tranexamic Acid for Hemostasis of an Oral Bleed in a Patient on a Direct Oral Anticoagulant. Boccio, E., Hultz, K., Wong, AH.[2022]

A systematic review of 57 studies involving 5,049 patients found that the antifibrinolytic drug tranexamic acid (TXA) has a low frequency of thrombotic events, with less than 1% incidence of limb ischaemia and myocardial infarction.

For patients treated with TXA or epsilonaminocaproic acid (EACA) after spontaneous bleeding, the occurrence of deep vein thrombosis or pulmonary embolism was 1.9% and 3.0%, respectively, indicating that these drugs are generally safe, especially outside of subarachnoid haemorrhage cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The frequency of thrombotic events among adults given antifibrinolytic drugs for spontaneous bleeding: systematic review and meta-analysis of observational studies and randomized trials. Ross, J., Al-Shahi Salman, R.[2022]

Tranexamic acid (TXA) significantly reduces perioperative blood loss in total shoulder arthroplasty (TSA), with a notable decrease in hemoglobin change, drain output, and total blood loss, particularly after reverse TSA, based on a meta-analysis of 6 studies involving 680 patients.

While TXA shows a trend towards reducing transfusion rates after reverse TSA, it did not significantly affect transfusion rates after anatomic TSA, indicating a need for further research to clarify its efficacy in different TSA types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid administration for anatomic and reverse total shoulder arthroplasty: a systematic review and meta-analysis. Box, HN., Tisano, BS., Khazzam, M.[2022]

Tranexamic acid (TXA) significantly reduces the rate of hematoma expansion in patients with traumatic brain injury (TBI), which can lead to lower mortality rates and improved neurologic outcomes, based on a systematic review of 5 randomized controlled trials involving 917 patients.

The effectiveness of TXA is enhanced when treatment is administered early, and it does not increase the risk of thrombosis events, indicating it is a safe option for managing hemorrhage in TBI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Tranexamic Acid in Patients with Traumatic Brain Injury: A Systematic Review and Meta-Analysis. Weng, S., Wang, W., Wei, Q., et al.[2019]

Tranexamic acid (TXA) significantly reduces total blood loss in patients undergoing hip arthroplasty, with a weighted mean difference favoring TXA compared to controls (P<0.001).

While there is a trend towards fewer patients requiring blood transfusions in the TXA group, this result was not statistically significant, indicating that TXA is effective for reducing bleeding but may not drastically lower transfusion needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficiency of tranexamic acid in perioperative blood loss in hip arthroplasty: a systematic literature review and meta-analysis. Pinzón-Florez, CE., Vélez Cañas, KM., Díaz Quijano, DM.[2018]

A systematic review and meta-analysis of four studies involving 2,347 trauma patients showed that prehospital administration of tranexamic acid (TXA) significantly reduces early mortality (within 24 hours) compared to no TXA, with an odds ratio of 0.60.

The use of TXA did not increase the risk of venous thromboembolism, indicating it is a safe intervention for managing bleeding in trauma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of prehospital TXA on mortality among bleeding trauma patients: A systematic review and meta-analysis. Almuwallad, A., Cole, E., Ross, J., et al.[2023]

References

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

Effect of age on the efficacy of tranexamic acid: An analysis of heterogeneity of treatment effect within the CRASH-2 dataset. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Statistical analysis plan for the 'Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage' (TICH-2) trial. [2023]

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

Evaluation of tranexamic acid in trauma patients: A retrospective quantitative analysis. [2019]

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

Topical Tranexamic Acid for Hemostasis of an Oral Bleed in a Patient on a Direct Oral Anticoagulant. [2022]

5. United Arab Emirates pubmed.ncbi.nlm.nih.gov

The frequency of thrombotic events among adults given antifibrinolytic drugs for spontaneous bleeding: systematic review and meta-analysis of observational studies and randomized trials. [2022]

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

Effect of tranexamic acid on thrombotic events and seizures in bleeding patients: a systematic review and meta-analysis. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Tranexamic acid administration for anatomic and reverse total shoulder arthroplasty: a systematic review and meta-analysis. [2022]

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

Effect of Tranexamic Acid in Patients with Traumatic Brain Injury: A Systematic Review and Meta-Analysis. [2019]

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

Mortality and Thrombosis in Injured Adults Receiving Tranexamic Acid in the Post-CRASH-2 Era. [2022]

10. England pubmed.ncbi.nlm.nih.gov

When to use tranexamic acid for the treatment of major bleeding? [2023]

11. England pubmed.ncbi.nlm.nih.gov

Trauma-targeted delivery of tranexamic acid improves hemostasis and survival in rat liver hemorrhage model. [2023]

12. Spain pubmed.ncbi.nlm.nih.gov

Efficiency of tranexamic acid in perioperative blood loss in hip arthroplasty: a systematic literature review and meta-analysis. [2018]

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

The Efficacy and Safety of Tranexamic Acid Treatment in Orthopaedic Trauma Surgery. [2023]

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

The impact of prehospital TXA on mortality among bleeding trauma patients: A systematic review and meta-analysis. [2023]