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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the timing of tranexamic acid, a medication that reduces bleeding, during heart surgery. Researchers aim to determine whether administering the medication before or after using a heart-lung machine affects its blood concentration and the body's ability to prevent bleeding. Suitable candidates for this trial include individuals undergoing specific heart surgeries, such as bypass or valve replacement, using a heart-lung machine, and who have no history of bleeding disorders. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that tranexamic acid is generally safe and reduces bleeding during heart surgery. Studies indicate its effectiveness in reducing blood loss, whether administered before or after using the heart-lung machine. This reduction in bleeding can lead to fewer blood transfusions.

However, some evidence suggests a potential risk of increased heart strain, particularly with higher doses. Caution is necessary, but the benefits in managing bleeding remain significant.

Overall, tranexamic acid is well-tolerated, and research strongly supports its benefits in controlling bleeding. This makes it a promising option, though some risks continue to be studied. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about the timing of tranexamic acid (TxA) for managing postoperative bleeding because it explores when the drug is administered to maximize its benefits. Unlike standard treatments that usually focus on consistent administration throughout surgery, this study investigates giving TxA either before or after cardiopulmonary bypass (CPB). The goal is to fine-tune the timing to reduce bleeding more effectively and potentially improve recovery times. By testing these specific timing strategies, researchers aim to optimize how TxA can be used for better patient outcomes, making it a potentially game-changing approach to surgical care.

What evidence suggests that this trial's treatments could be effective for postoperative bleeding?

This trial will compare the timing of tranexamic acid (TXA) administration to reduce postoperative bleeding. Studies have shown that TXA reduces blood loss and the need for blood transfusions during and after surgery. Research indicates that TXA decreases bleeding and the risk of needing another surgery without increasing the chance of blood clots. It is particularly useful in surgeries like hip and thigh bone surgeries, where it significantly reduces blood loss. Additionally, TXA has proven effective in lowering the risk of bleeding when used before surgery and for a short time afterward. Overall, TXA is considered safe and effective for reducing bleeding in various types of surgery. ^{6 7 8 9 10}

Who Is on the Research Team?

Andre Lamy

Principal Investigator

Hamilton General Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3657919/

Role of tranexamic acid in reducing postoperative blood ... We conclude that tranexamic acid significantly reduces postoperative blood loss and transfusion requirements during major hip and femoral surgeries.

2. journals.lww.com journals.lww.com/prsgo/fulltext/2023/11000/effectiveness_of_tranexamic_acid_in_the.31.aspx

Effectiveness of Tranexamic Acid in the Postoperative... ... TXA proved to be more effective in reducing intra- and postsurgical bleeding and the need for transfusions, when used preoperatively and continued for 48 hours ...

3. thrombosisjournal.biomedcentral.com thrombosisjournal.biomedcentral.com/articles/10.1186/s12959-021-00303-9

Tranexamic acid for the prevention and treatment of bleeding ... The results demonstrated that TXA reduced blood loss, blood transfusion and reintervention, without increasing the risk of thrombotic ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39813061/

Safety and Efficacy of Tranexamic Acid in General Surgery In this study, TXA significantly reduced the risk of perioperative bleeding without increasing cardiovascular risk in patients undergoing general surgery ...

5. jamanetwork.com jamanetwork.com/journals/jamasurgery/article-abstract/2829135?fbclid=IwY2xjawIC47lleHRuA2FlbQIxMQABHS0r_d8lJ9av-Km_kix0GDI7MUhOQTmLhkI5BxyT_u7J72CZAxaEPgpnpA_aem_KPcmrUHhPFzYwtYNRHk1sg

Safety and Efficacy of Tranexamic Acid in General Surgery Conclusions and Relevance In this study, TXA significantly reduced the risk of perioperative bleeding without increasing cardiovascular risk in patients ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12595628/

Effectiveness and safety of low-dose intraoperative ... The routine implementation of low-dose intraoperative TXA in cardiac surgery was associated with a significant reduction in bleeding after ...

7. bmcanesthesiol.biomedcentral.com bmcanesthesiol.biomedcentral.com/articles/10.1186/s12871-025-03365-8

Efficacy and safety of tranexamic acid in cardiac surgery Both intravenous and topical TXA administration reduce postoperative blood loss. High-dose continuous administration further reduces the risk of ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa1606424

Tranexamic Acid in Patients Undergoing Coronary-Artery ... Tranexamic acid reduces the risk of bleeding among patients undergoing cardiac surgery, but it is unclear whether this leads to improved outcomes.

9. sciencedirect.com sciencedirect.com/science/article/pii/S016752732102009X

Blood conservation outcomes and safety of tranexamic ... The use of TXA during CABG increased the risk of PMI despite better blood control after surgery. The high dose of TXA acquired better bleeding management.

10. cts.springeropen.com cts.springeropen.com/articles/10.1186/s43057-025-00175-z

Current views on topical tranexamic acid in cardiac surgery ... It concluded that topical TXA is as effective as IV TXA in reducing postoperative bleeding. Results also indicate that topical TXA can reduce ...