LTOWB + TXA for Hemorrhagic Shock

(MATIC-2 Trial)

Recruiting at 24 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates two treatments for children under 18 with severe bleeding from traumatic injuries who might require extensive blood transfusions. The researchers aim to determine if Low Titer Group O Whole Blood (LTOWB) is more effective than the usual component therapy and if Tranexamic Acid (TXA) reduces death within 24 hours more effectively than a placebo. The trial includes four groups, each receiving different combinations of these treatments or placebos. Suitable candidates for this trial are children with traumatic injuries experiencing severe bleeding, indicated by symptoms such as low blood pressure, rapid heartbeat, or visible severe injuries. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially life-saving treatments.

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 Low Titer Group O Whole Blood (LTOWB) is generally safe for patients needing rapid intervention, such as those with severe bleeding. One study demonstrated that LTOWB improved survival rates for patients in shock without causing major side effects. Another study found it safe and practical for use in emergencies before hospital arrival.

For Tranexamic Acid (TXA), studies have indicated it is well-tolerated in various situations. The FDA has already approved it for controlling bleeding in other conditions, providing reassurance about its safety.

Both treatments have been used in emergencies and have demonstrated positive safety records, suggesting they are relatively safe options for managing severe bleeding in children. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment using Low Titer Group O Whole Blood (LTOWB) and Tranexamic Acid (TXA) for hemorrhagic shock because it combines a universal blood type with a medication known to stabilize blood clots. Unlike standard care, which often involves separate blood transfusions and clot-stabilizing drugs, this approach delivers both in tandem, potentially improving the speed and efficiency of treatment. The unique aspect of using LTOWB is its compatibility with all blood types, reducing delays in emergency settings. Meanwhile, TXA works by preventing the breakdown of blood clots, crucial in managing severe bleeding. This combination aims to enhance survival rates by addressing both blood volume replacement and clot stability simultaneously.

What evidence suggests that this trial's treatments could be effective for hemorrhagic shock?

This trial will evaluate the effectiveness of Low Titer Group O Whole Blood (LTOWB) and Tranexamic Acid (TXA) in treating hemorrhagic shock. Research has shown that LTOWB might be a good option for treating severe blood loss in children, as it can be administered quickly and has balanced components. However, some research indicates it may not always surpass traditional blood treatments. For TXA, studies have found it can significantly reduce early death rates in trauma patients. Specifically, one study showed that administering TXA early lowered 24-hour death rates from 12.8% to 5.8%. Participants in this trial will receive either LTOWB with TXA, LTOWB with a placebo, CT with TXA, or CT with a placebo. Both LTOWB and TXA have shown promise in improving survival after significant blood loss. ^{2 6 7 8 9}

Who Is on the Research Team?

Philip C Spinella, MD

Principal Investigator

Univesrity of Pittsburgh

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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 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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39332971/

Review of Low Titer Group O Whole Blood (LTOWB ... LTOWB transfusion appears to be a promising option for pediatric trauma resuscitation, offering benefits in rapid administration and component balance.

2. sciencedirect.com sciencedirect.com/science/article/pii/S1538783623007274

Doing more with less: low-titer group O whole blood ... We hypothesized LTOWB would improve 24-hour survival in hemorrhaging patients and would be safe and equally efficacious in non–group O compared with group O ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9038638/

PREHOSPTIAL LOW TITER GROUP O WHOLE BLOOD IS ... The current high-level data regarding the safety and efficacy of whole blood in the prehospital setting is limited and a definitive trial is needed to justify ...

4. jpedsurg.org jpedsurg.org/article/S0022-3468(24)00794-2/abstract

Review of Low Titer Group O Whole Blood (LTOWB ... Clinical outcomes exhibited no significant differences in mortality, hospital, or ventilator days between LTOWB and component therapy (CT).

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05638581

NCT05638581 | Trauma Resuscitation With Low-Titer ... The goal of this clinical trial is to compare the effectiveness of unseparated whole blood (referred to as Low-Titer Group O Whole Blood) and the separate ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12035991/

Characterizing low titer group O whole blood (LTOWB) use in ... Data regarding low titer group O whole blood (LTOWB) use for hemostatic resuscitation is largely derived from trauma cohorts; studies regarding ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06070350

Massive Transfusion in Children-2: A Trial Examining Life ... 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 ...

8. journals.lww.com journals.lww.com/jtrauma/fulltext/2022/11000/prehospital_low_titer_group_o_whole_blood_.26.aspx

Prehospital low titer group O whole blood: Difficult to... Prehosptial low titer group O whole blood is feasible and safe: results of a prospective randomized pilot trial [published online June 14, 2022].

9. tsaco.bmj.com tsaco.bmj.com/content/10/2/e001828

whole blood and plasma in prehospital hemorrhagic shock ... Prehospital plasma administration reduces 30-day mortality by 9.8% in trauma patients at risk of hemorrhagic shock, particularly when transport times exceed 20 ...