LTOWB + TXA for Hemorrhagic Shock

(MATIC-2 Trial)

Recruiting at 22 trial locations

Overseen By Jane Luce

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Philip Spinella

Must not be taking: Tranexamic acid

Disqualifiers: Traumatic brain injury, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 hours

1000 Participants Needed

Trial Summary

What is the purpose of this trial?

The MATIC-2 is a multicenter clinical trial enrolling children who are less than 18 years of age with hemorrhagic shock potentially needing significant blood transfusion. The primary objective of the clinical trial is to determine the effectiveness of Low Titer Group O Whole Blood (LTOWB) compared to component therapy (CT), and Tranexamic Acid (TXA) compared to placebo in decreasing 24-hour all-cause mortality in children with traumatic life threatening hemorrhage.

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 LTOWB + TXA for Hemorrhagic Shock?

Research shows that tranexamic acid (TXA) can reduce blood loss and improve survival in trauma patients, which suggests it might help in treating hemorrhagic shock by reducing bleeding. ^{1 2 3 4 5}

How is the LTOWB + TXA treatment different from other treatments for hemorrhagic shock?

The LTOWB + TXA treatment is unique because it combines low titer group O whole blood, which can be universally given to any blood type, with tranexamic acid (TXA), an antifibrinolytic drug that helps reduce blood loss by preventing the breakdown of blood clots. This combination aims to quickly stabilize patients with hemorrhagic shock by addressing both blood volume and clot stability. ^{1 4 6 7 8}

Research Team

Philip C Spinella, MD

Principal Investigator

Univesrity of Pittsburgh

Eligibility Criteria

The MATIC-2 trial is for children under 18 with traumatic injuries and signs of severe bleeding, like low blood pressure or fast heart rate for their age. They must be suspected to need a massive transfusion due to life-threatening hemorrhage.

Inclusion Criteria

My child is under 18 and has a traumatic injury.

I have had a severe injury with significant bleeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either LTOWB or CT and Tranexamic Acid or placebo to assess effectiveness in reducing 24-hour mortality

24 hours

Continuous monitoring during treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including survival and adverse events

28 days

Regular follow-up visits

Treatment Details

Interventions

• Low Titer Group O Whole Blood (LTOWB)
• Tranexamic Acid (TXA)

Trial Overview This study tests if Low Titer Group O Whole Blood (LTOWB) or Tranexamic Acid (TXA) can lower the risk of death within 24 hours better than standard component therapy (CT) or placebo in kids with serious trauma and bleeding.

Participant Groups

Group I: Group 4 (CT+Placebo) Experimental Treatment 2 Interventions

Concurrent administration of CT and Placebo

Group II: Group 3 (CT+TXA) Experimental Treatment 2 Interventions

Concurrent administration of CT and TXA

Group III: Group 2 (LTOWB+Placebo) Experimental Treatment 2 Interventions

Concurrent administration of LTOWB and Placebo

Group IV: Group 1 (LTOWB+TXA) Experimental Treatment 2 Interventions

Concurrent administration of LTOWB and TXA

Low Titer Group O Whole Blood (LTOWB) is already approved in United States for the following indications:

Approved in United States as Low Titer Group O Whole Blood for:

• Traumatic life-threatening hemorrhage
• Massive bleeding

Who Is Running the Clinical Trial?

Philip Spinella

Lead Sponsor

Trials

2

Recruited

2,000+

Biomedical Advanced Research and Development Authority

Collaborator

Trials

108

Recruited

574,000+

Findings from Research

In a study involving 22 anesthetized pigs, tranexamic acid (TXA) effectively inhibited fibrinolysis but did not significantly reduce blood loss or improve survival compared to normal saline when used with hypotensive resuscitation methods.

Fresh frozen plasma (FFP) was found to significantly reduce blood loss and improve survival compared to Hextend (HEX), suggesting that while TXA has antifibrinolytic properties, it may not be effective in this specific model of uncontrolled hemorrhage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blinded, placebo-controlled study of early tranexamic acid treatment in swine uncontrolled hemorrhage model. Sondeen, JL., Hanson, MA., Prince, MD., et al.[2015]

The meta-analysis of seven clinical studies found that using both topical and intravenous tranexamic acid (TXA) significantly reduced the need for blood transfusions, total blood loss, and hemoglobin drop in patients undergoing total knee arthroplasty compared to IV TXA alone or a control group.

No significant differences in complications such as deep venous thrombosis, pulmonary embolism, or infections were observed between the combined TXA treatment and other groups, indicating that the combined approach is safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of combined intra-articular and intravenous tranexamic acid for blood loss in primary total knee arthroplasty: A meta-analysis. Wang, Z., Shen, X.[2022]

In a pilot study involving 20 patients undergoing cardiac surgery, a tranexamic acid (TXA) regimen effectively maintained TXA concentrations above 15 mg/L during and after cardiopulmonary bypass (CPB), which is crucial for reducing bleeding.

The TXA regimen significantly inhibited plasmin generation by 60% during and after CPB, indicating its efficacy in reducing fibrinolysis, with maximum inhibition observed 15 minutes after protamine administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pharmacokinetic and Plasmin-Generation Pharmacodynamic Assessment of a Tranexamic Acid Regimen Designed for Cardiac Surgery With Cardiopulmonary Bypass. Strauss, ER., Li, S., Henderson, R., et al.[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]

In a study of 60 patients undergoing bilateral total knee arthroplasty, intravenous tranexamic acid (TXA) significantly reduced total blood loss and the need for blood transfusions compared to the control group, indicating its efficacy in managing perioperative blood loss.

The use of TXA did not increase the risk of deep vein thrombosis or other thromboembolic events, suggesting it is a safe option for patients undergoing knee surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A PROSPECTIVE RANDOMIZED SELF-CONTROLLED STUDY ON EFFECT OF TRANEXAMIC ACID IN REDUCING BLOOD LOSS IN TOTAL KNEE ARTHROPLASTY]. Huang, Z., Zhang, W., Li, W., et al.[2018]

In a study of 234 severely injured trauma patients with severe traumatic brain injury, prehospital administration of tranexamic acid (TXA) did not lead to improved outcomes compared to those who did not receive TXA, despite TXA patients having more severe initial conditions.

The study found a low rate of thromboembolic complications (6%) associated with TXA use, suggesting that while TXA is generally safe, it does not significantly impact mortality or recovery in polytrauma patients with critical brain injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of prehospital tranexamic acid on outcome in polytrauma patients with associated severe brain injury. van Wessem, KJP., Jochems, D., Leenen, LPH.[2022]

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]

In a study of 529 patients with acute type A aortic dissection undergoing surgery, high-dose tranexamic acid (TXA) significantly reduced postoperative blood loss compared to low-dose TXA, with a reduction from 940 mL to 695 mL within the first 3 days after surgery.

Total postoperative blood loss was also lower in the high-dose group (1,890 mL) compared to the low-dose group (2,040 mL), while there were no differences in blood transfusion needs or safety outcomes between the two dosage groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Tranexamic Acid in Patients Underwent Surgical Repair of Aortic Dissection Might Reduce Postoperative Blood Loss: A Cohort Analysis. Guo, J., Cao, L., Wang, H., et al.[2022]

References

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

Double-blinded, placebo-controlled study of early tranexamic acid treatment in swine uncontrolled hemorrhage model. [2015]

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

The efficacy of combined intra-articular and intravenous tranexamic acid for blood loss in primary total knee arthroplasty: A meta-analysis. [2022]

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

A Pharmacokinetic and Plasmin-Generation Pharmacodynamic Assessment of a Tranexamic Acid Regimen Designed for Cardiac Surgery With Cardiopulmonary Bypass. [2022]

4. France pubmed.ncbi.nlm.nih.gov

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

5. China pubmed.ncbi.nlm.nih.gov

[A PROSPECTIVE RANDOMIZED SELF-CONTROLLED STUDY ON EFFECT OF TRANEXAMIC ACID IN REDUCING BLOOD LOSS IN TOTAL KNEE ARTHROPLASTY]. [2018]

6. Germany pubmed.ncbi.nlm.nih.gov

The effect of prehospital tranexamic acid on outcome in polytrauma patients with associated severe brain injury. [2022]

7. 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]

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

High-Dose Tranexamic Acid in Patients Underwent Surgical Repair of Aortic Dissection Might Reduce Postoperative Blood Loss: A Cohort Analysis. [2022]