Tranexamic Acid Timing for Postoperative Bleeding

(DEPOSITION-2 Trial)

Overseen By Patricia Power

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hamilton Health Sciences Corporation

Disqualifiers: Allergy to tranexamic acid, Bleeding disorder, Thrombocytopenia, Pregnancy, others

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

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 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: During surgery

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

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 reducing postoperative bleeding?

Research shows that Tranexamic Acid (TXA) is effective in reducing blood loss and the need for blood transfusions in various surgeries, including shoulder and trauma surgeries. This suggests it may also help with postoperative bleeding by minimizing blood loss. ^{1 2 3 4 5}

Is tranexamic acid safe for humans?

Tranexamic acid (TXA) is generally considered safe for humans, as it has been shown to reduce bleeding and mortality in trauma patients and is used safely in various surgeries. However, its effects on blood clots and seizures are less clear, and further studies are needed to fully understand its safety in different conditions. ^{1 6 7 8 9}

How is the drug tranexamic acid unique for treating postoperative bleeding?

Tranexamic acid (TXA) is unique because it helps reduce blood loss by stabilizing blood clots, and its timing of administration can be adjusted to optimize effectiveness, such as using it at different stages of surgery or extending its use postoperatively. ^{1 3 10 11 12}

What is the purpose of this trial?

The goal of this clinical trial is to establish the feasibility of conducting a large trial to determine the optimal timing of intravenous tranexamic acid administration in cardiac surgery. The main questions it aims to answer are: * Is it feasible to conduct a larger definitive trial? * Can we measure the systemic tranexamic acid concentration and fibrinolytic potential in the blood samples? Researchers will compare intravenous tranexamic acid administered before cardiopulmonary bypass versus after cardiopulmonary bypass to see if the systemic tranexamic acid concentration and fibrinolytic potential are similar or better. Participants will: * Provide written informed consent * Receive tranexamic acid during surgery * Provide blood samples at 5 time points: before surgery, on arrival in intensive care unit, 3 hours after arrival, 6 hours after arrival, and on the next morning.

Research Team

Andre Lamy

Principal Investigator

Hamilton General Hospital

Eligibility Criteria

This trial is for individuals undergoing cardiac surgery who are willing to provide informed consent, receive tranexamic acid during their operation, and give blood samples at specified times before and after the surgery. Specific eligibility criteria have not been detailed.

Inclusion Criteria

I am having heart surgery that requires a heart-lung machine.

Provide written informed consent

Exclusion Criteria

Pre-operative hemoglobin >170 g/L

Expected circulatory arrest

I refuse blood transfusions due to personal beliefs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous tranexamic acid during cardiac surgery, with administration either before or after cardiopulmonary bypass

During surgery

1 visit (in-person)

Post-operative Monitoring

Blood samples are collected at 5 time points to measure systemic tranexamic acid concentration and fibrinolytic potential

Up to 10 days

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including the occurrence of seizures and need for transfusions

Up to 10 days or until hospital discharge

Treatment Details

Interventions

• Tranexamic Acid

Trial Overview The study tests whether giving intravenous tranexamic acid before or after cardiopulmonary bypass affects blood loss and seizure rates post-surgery. It's a pilot study to see if a larger trial would be feasible and will measure drug levels in the blood.

Participant Groups

Group I: After CPB Tranexamic Acid/Placebo Active Control 2 Interventions

In the intervention group, patients will receive intravenous administration (10-100 mL of saline placebo) at the induction of anesthesia as a bolus and/or continuous infusion. In addition, patients will receive intravenous administration (5 g of TxA) after heparin reversal (i.e., after CPB).

Group II: Before CPB Tranexamic Acid/Placebo Active Control 2 Interventions

In the control group, patients will receive an intravenous administration (1-10 g of TxA) at the induction of anesthesia as a bolus and/or continuous infusion (i.e., before CPB). In addition, patients will receive an intravenous administration (50 mL of saline placebo) after heparin reversal.

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?

Hamilton Health Sciences Corporation

Lead Sponsor

Trials

380

Recruited

345,000+

Findings from Research

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]

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]

In a study of 9,276 shoulder arthroplasties, the use of preoperative tranexamic acid (TXA) did not significantly reduce the risk of revision due to deep infection within 5 years, showing a 5-year infection revision probability of 0.8% for TXA users and 0.7% for non-users.

The analysis indicated no difference in infection risk for patients with or without diabetes, suggesting that TXA may not provide the expected protective effect against postoperative infections in shoulder arthroplasty.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid is not associated with decreased infection risk after primary shoulder arthroplasty: a cohort study of 9276 patients. Gorbaty, J., Chan, PH., McElvany, MD., et al.[2023]

Tranexamic acid (TxA) significantly reduces the volume of hematomas after total knee arthroplasty (TKA), with a decrease from 526 mL in the control group to 337 mL in the TxA group, indicating its efficacy in minimizing blood loss.

Despite the reduction in hematoma volume, TxA did not lead to a significant decrease in morphine consumption for pain management or improve rehabilitation outcomes within the first six months post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Tranexamic acid reduces haematomas but not pain after total knee arthroplasty]. Chevet, I., Remérand, F., Couvret, C., et al.[2013]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Update on Applications and Limitations of Perioperative Tranexamic Acid. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Prehospital tranexamic acid shortens the interval to administration by half in Major Trauma Networks: a service evaluation. [2020]

4. 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]

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

Tranexamic acid is not associated with decreased infection risk after primary shoulder arthroplasty: a cohort study of 9276 patients. [2023]

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

Effects of tranexamic acid on short-term and long-term outcomes of on-pump coronary artery bypass grafting: Randomized trial and 7-year follow-up. [2019]

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

Role of Tranexamic Acid in the Clinical Setting. [2020]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Is Combined Administration of Tranexamic Acid Better than Both Intravenous and Topical Regimes for Total Loss, Hidden Loss and Post-operative Swelling? A Randomized Control Trial. [2022]

9. 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]

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

Effect of Tranexamic Acid on Postoperative Bleeding in Sleeve Gastrectomy: a Randomized Trial. [2023]

11. France pubmed.ncbi.nlm.nih.gov

[Tranexamic acid reduces haematomas but not pain after total knee arthroplasty]. [2013]

12. England pubmed.ncbi.nlm.nih.gov

Assessment of the effect of addition of 24 hours of oral tranexamic acid post-operatively to a single intraoperative intravenous dose of tranexamic acid on calculated blood loss following primary hip and knee arthroplasty (TRAC-24): a study protocol for a randomised controlled trial. [2019]