Tranexamic Acid + Desmopressin for Reducing Surgical Bleeding

(BRACKETS Trial)

Overseen By Ingrid Copland

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hamilton Health Sciences Corporation

Must not be taking: Prophylactic TXA, Desmopressin

Disqualifiers: Cardiac surgery, Seizure disorder, Stroke, 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

Compensation: Varies

Number of Visits: 1

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two medications, tranexamic acid and desmopressin, to determine their effectiveness in reducing bleeding during surgery. Participants will be randomly assigned to receive either one or both of these medications, or a placebo (a substance with no active medicine), before surgery. The goal is to identify which treatment, if any, most effectively controls bleeding. Suitable candidates for this trial include individuals with kidney problems requiring dialysis or low kidney function, scheduled for non-heart surgery that requires at least one night in the hospital. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

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

The trial information does not specify if 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 both desmopressin and tranexamic acid are safe for controlling bleeding in various surgeries. Studies have found that desmopressin lowers bleeding and reduces the need for blood transfusions during heart surgeries. It has been used without causing infections, making it a reliable choice for managing blood loss.

Tranexamic acid is also safe and effective in reducing bleeding during surgeries, including general surgeries and C-sections, and does not appear to increase the risk of heart problems.

When used together, tranexamic acid and desmopressin effectively reduce bleeding in spinal surgeries. This combination is considered safe, and each medication is usually well-tolerated on its own.

Both treatments have been studied for their safety and effectiveness, providing reassurance for those considering participation in clinical trials involving these drugs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of tranexamic acid and desmopressin for reducing surgical bleeding because it offers a potentially more effective way to control bleeding during surgery. Unlike standard treatments that might focus on just one pathway to reduce bleeding, this combination targets multiple mechanisms. Tranexamic acid helps by stabilizing clots, while desmopressin increases levels of clotting factors in the blood. This dual approach could lead to better outcomes for patients who undergo surgery, providing enhanced bleeding control compared to existing options.

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

Research has shown that tranexamic acid (TXA) reduces blood loss during surgery and decreases the need for blood transfusions without increasing the risk of blood clots. Desmopressin also reduces blood loss and the need for transfusions, particularly in heart surgeries. In this trial, participants may receive TXA, desmopressin, or a combination of both. Using TXA and desmopressin together enhances their effectiveness in controlling bleeding and reducing the need for transfusions during surgery. ^{2 3 6 7 8}

Who Is on the Research Team?

Pavel Roshanov, MC,MSc,FRCPC

Principal Investigator

Western University

Are You a Good Fit for This Trial?

The BRACKETS pilot trial is for patients with severe kidney problems who are planning noncardiac surgery. They must have very low kidney function or be on dialysis, and they're expected to stay in the hospital overnight after surgery. Participants need to give informed consent.

Inclusion Criteria

I am scheduled for a surgery that is not related to the heart.

Informed consent is obtained to participate in the BRACKETS-Pilot Trial

Included in the TXA factorial

Exclusion Criteria

I am scheduled for heart surgery.

Previously enrolled in the BRACKETS-Pilot Trial

Hypersensitivity or known allergy to TXA

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Administration

Participants receive preoperative prophylactic intravenous tranexamic acid or desmopressin, or placebo, within 20 minutes preceding anticipated skin incision

Day of surgery

1 visit (in-person)

Postoperative Monitoring

Participants are monitored for safety and effectiveness, including assessment of various outcomes such as bleeding, stroke, and other complications

30 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

What Are the Treatments Tested in This Trial?

Interventions

• Desmopressin
• Tranexamic Acid

Trial Overview This study tests if giving tranexamic acid (TXA) or desmopressin before surgery can reduce bleeding in patients with acute or chronic kidney issues. It's a randomized trial where some get TXA, others get desmopressin, and there's also a placebo group.

How Is the Trial Designed?

Group I: Prophylactic intravenous tranexamic acid and prophylactic intravenous desmopressin. Experimental Treatment 2 Interventions

Within 20 minutes preceding anticipated skin incision, patients will receive preoperative prophylactic intravenous tranexamic acid at a dose of 1000 mg infused over 10 minutes for patients with estimated glomerular filtration rate (eGFR) \<25 ml/min/1.73m2 who do not receive dialysis before surgery and 500 mg infused over 10 minutes for patients who receive dialysis. Within 20 minutes preceding anticipated skin incision, patients allocated to the desmopressin intervention group will receive intravenous desmopressin at a dose of 20 mcg over 30 minutes.

Group II: Prophylactic intravenous tranexamic acid and placebo. Experimental Treatment 2 Interventions

Within 20 minutes preceding anticipated skin incision, patients will receive preoperative prophylactic intravenous tranexamic acid at a dose of 1000 mg infused over 10 minutes for patients with eGFR \<25 ml/min/1.73m2 who do not receive dialysis before surgery and 500 mg infused over 10 minutes for patients who receive dialysis. Within 20 minutes preceding anticipated skin incision, patients allocated to the desmopressin control group will receive an intravenous infusion of 0.9% saline solution, administered over a duration of 30 minutes.

Group III: Prophylactic intravenous desmopressin and placebo. Experimental Treatment 2 Interventions

Within 20 minutes preceding anticipated skin incision, patients will receive intravenous desmopressin at a dose of 20 mcg over 30 minutes. Patients will not receive prophylactic tranexamic acid. Within 20 minutes preceding anticipated skin incision, patients allocated to the tranexamic acid control group will receive an intravenous infusion of 0.9% saline solution. This saline solution will be administered over a duration of 10 minutes in a volume equivalent to that received by patients in the tranexamic acid intervention group.

Group IV: Placebo and placebo. Placebo Group 1 Intervention

Within 20 minutes preceding anticipated skin incision, patients allocated to the tranexamic acid control group will receive an intravenous infusion of 0.9% saline solution. This saline solution will be administered over a duration of 10 minutes in a volume equivalent to that received by patients in the tranexamic acid intervention group. Within 20 minutes preceding anticipated skin incision, patients allocated to the desmopressin control group will receive an intravenous infusion of 0.9% saline solution, administered over a duration of 30 minutes.

Who Is Running the Clinical Trial?

Hamilton Health Sciences Corporation

Lead Sponsor

Trials

380

Recruited

345,000+

Population Health Research Institute

Collaborator

Trials

165

Recruited

717,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10804695/

Desmopressin to reduce periprocedural bleeding and ... Compared with either placebo or usual care, desmopressin resulted in a small reduction in total volume of blood loss (SMD − 0.40, 95% CI − 0.56 ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1443950625000277

Efficacy and Safety of Desmopressin in Terms of Bleeding ... Results of the present meta-analysis demonstrated that desmopressin reduced blood loss and the amount of red blood cell transfusions after cardiac surgery.

3. nejm.org nejm.org/doi/full/10.1056/NEJM199004123221515

Desmopressin and Surgical Hemostasis Treatment with desmopressin acetate to reduce blood loss after cardiac surgery: a double-blind randomized trial. N Engl J Med 1986; 314:1402 ...

4. www1.wfh.org www1.wfh.org/publication/files/pdf-1131.pdf

DESMOPRESSIN (DDAVP) IN THE TREATMENT OF ... - WFH Evaluation of the effectiveness of DDAVP in surgery and bleeding episodes in hemophilia and von. Willebrand's disease. A study of 43 patients. Clin Lab.

5. ashpublications.org ashpublications.org/blood/article/145/16/1814/535276/DDAVP-response-and-its-determinants-in-bleeding

DDAVP response and its determinants in bleeding disorders The main outcome was proportion of patients with complete (factor level >50 U/dL) or partial (30-50 U/dL) response to DDAVP. Determinants of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10461384/

Effect of Desmopressin on Bleeding After Heart Surgeries 4. Conclusions. Various studies show that desmopressin in adults undergoing heart surgery significantly reduces bleeding and the need for transfusion of blood ...

7. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/lio2.841

Effect of desmopressin on bleeding during endoscopic ... The present study showed that the use of desmopressin at a dose of 40 μg 1 h before surgery can reduce bleeding and improve the quality of the surgical field.

8. jcvaonline.com jcvaonline.com/article/S1053-0770(17)30207-0/fulltext

The use of desmopressin (DDAVP) as haemostatic agent ... Desmopressin has been used as an inexpensive blood saving agent in CABG surgery without the risk of transmitting blood-borne infections.