Low Titer Whole Blood for Hemorrhagic Shock

(TOWAR Trial)

Recruiting at 10 trial locations

Overseen By Jason Sperry, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Jason Sperry

Disqualifiers: Age > 90, < 18, 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 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

1020 Participants Needed

Trial Summary

What is the purpose of this trial?

Open label, multi-center, pre-hospital randomized trial utilizing 10 level-1 trauma centers designed to determine the efficacy and safety of low titer whole blood resuscitation as compared to standard of care resuscitation in patients at risk of hemorrhagic shock and to appropriately characterize the hemostatic competency of whole blood relative to its age.

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

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Low Titer Whole Blood for Hemorrhagic Shock?

Research shows that using low-titer group O whole blood (LTOWB) for treating severe bleeding improves survival rates compared to other blood component therapies. Studies also indicate that LTOWB reduces early death in patients with hemorrhagic shock when used before reaching the hospital. ^{1 2 3 4 5}

Is low titer whole blood safe for humans?

Research shows that low titer group O whole blood (LTOWB) is generally safe for use in both adults and children, with studies indicating improved survival rates and fewer blood transfusions needed in trauma patients. While there is limited data on adverse events, its use in pediatric trauma has been shown to be safe when specific precautions are taken. ^{1 2 3 5 6}

How is Low Titer Whole Blood treatment different for hemorrhagic shock?

Low Titer Whole Blood (LTOWB) is unique because it combines all blood components in one transfusion, providing a balanced resuscitation that can improve survival rates compared to traditional component therapy, which separates blood into parts like red cells and plasma. This approach is especially beneficial in emergency settings, as it simplifies the transfusion process and reduces the need for multiple transfusions. ^{2 3 5 7 8}

Research Team

Jason Sperry, MD, MPH

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for people with severe injuries at risk of hemorrhagic shock who have very low blood pressure. It's open to adults aged 18-90, not including pregnant individuals, prisoners, or those with specific types of brain injuries and other exclusions like drowning or hanging victims without other trauma.

Inclusion Criteria

Systolic blood pressure ≤ 70mmHg at scene, at outside hospital or during transport

I am at risk of severe bleeding and being taken to a hospital for a blood transfusion.

My blood pressure was 90 or lower and my heart rate was 108 or higher.

Exclusion Criteria

Wearing NO TOWAR opt-out bracelet

Doctors cannot use veins or bones for my treatments.

You have only fallen from a standing position and not experienced any other injury mechanism.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Prehospital Resuscitation

Participants receive either whole blood or standard care resuscitation in the prehospital phase

Immediate

1 visit (in-person)

In-hospital Monitoring

Participants are monitored for various outcomes including mortality, infections, and organ failure

Up to 30 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Low Titer Whole Blood
• Standard Care

Trial Overview The study compares the effectiveness and safety of using low titer whole blood versus standard care in pre-hospital settings for patients at risk of bleeding out. It involves multiple trauma centers and looks at how well the donated blood works based on its age.

Participant Groups

Group I: Whole Blood Experimental Treatment 1 Intervention

Subjects will receive up to two units of whole blood as collected by local blood bank procedures and stored at 1-6 degrees Celsius initiated in the prehospital phase of care.

Group II: Standard Care Active Control 1 Intervention

Subjects will receive prehospital crystalloid infusion or blood component transfusion resuscitation per site standard care for the respective Emergency Medical unit/service.

Low Titer Whole Blood is already approved in United States for the following indications:

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

• Hemorrhagic shock
• Trauma resuscitation

Who Is Running the Clinical Trial?

Jason Sperry

Lead Sponsor

Trials

9

Recruited

6,900+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

In a study comparing 602 patients receiving packed red blood cells (pRBC) and 749 patients receiving low-titer group O whole blood (LTOWB) for emergency transfusions, LTOWB was associated with a significant increase in total blood product use at both 24 hours and 7 days post-transfusion.

Despite the increased blood use, the initial use of LTOWB did not lead to improved survival rates or reduced non-lethal adverse clinical outcomes compared to pRBC, indicating no clear advantage of LTOWB in emergency settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emergency transfusion with whole blood versus packed red blood cells: A study of 1400 patients. Ruby, KN., Dzik, WH., Collins, JJ., et al.[2023]

In a study involving trauma patients receiving massive transfusions, the use of low-titer group O whole blood (LTOWB) was associated with a 23% increase in the odds of survival at 24 hours compared to component therapy, indicating its potential efficacy in improving short-term outcomes.

LTOWB also showed improved survival rates at 28 days without increasing organ dysfunction, particularly benefiting patients with lower clot firmness (maximum clot firmness ≤60 mm), suggesting it may be a safer and more effective option for hemostatic resuscitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of low-titer group O whole blood is independently associated with improved survival compared to component therapy in adults with severe traumatic hemorrhage. Shea, SM., Staudt, AM., Thomas, KA., et al.[2021]

In a study comparing 36 pediatric patients receiving low titer group O whole blood (LTOWB) to 36 receiving conventional red blood cell components, there were no significant differences in adverse events such as transfusion reactions, organ failure, or acute kidney injury.

The LTOWB group experienced a significantly shorter ICU length of stay compared to the component group, suggesting that LTOWB may be a safe and effective initial resuscitative fluid in pediatric trauma without increasing adverse outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events after low titer group O whole blood versus component product transfusion in pediatric trauma patients: A propensity-matched cohort study. Leeper, CM., Yazer, MH., Morgan, KM., et al.[2021]

In a study of 167 trauma patients receiving massive transfusions, there was no significant difference in 24-hour survival rates between those receiving leukocyte reduced low-titer group O whole blood (LR-LTOWB) and those receiving non-leukocyte reduced LTOWB.

Both types of transfusions were safe, with no reported adverse events, suggesting that the choice between LR and non-LR LTOWB may not impact short-term survival outcomes in hemorrhagic shock cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison between leukocyte reduced low titer whole blood vs non-leukocyte reduced low titer whole blood for massive transfusion activation. Fadeyi, EA., Saha, AK., Naal, T., et al.[2021]

Patients receiving low titer O+ whole blood (LTOWB) transfusions in the prehospital setting showed a significant improvement in their shock index and a reduction in early mortality compared to those who did not receive transfusions, indicating its efficacy in managing hemorrhagic shock.

However, there was no observed survival benefit for patients in prehospital cardiac arrest receiving LTOWB, suggesting that while LTOWB can be beneficial for trauma patients, its effectiveness may vary based on the clinical scenario.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prehospital whole blood reduces early mortality in patients with hemorrhagic shock. Braverman, MA., Smith, A., Pokorny, D., et al.[2021]

In a study of 164 pediatric trauma patients, the use of non-leukoreduced low-titer group O whole blood (LTOWB) with anti-A/anti-B antibody titers of <1:200 was found to be safe, showing no significant differences in hemolysis markers compared to those receiving only red blood cells and plasma.

While there was no initial difference in survival rates, adjusted analyses suggested that LTOWB administration may be associated with improved survival, indicating a potential mortality benefit despite the higher severity of injuries in those receiving LTOWB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An assessment of the safety, hemostatic efficacy, and clinical impact of low-titer group O whole blood in children and adolescents. Gerard, J., Mueck, K., Lubkin, D., et al.[2023]

Transfusion of low-titer group O whole blood (LTOWB) in trauma patients resulted in a smaller decrease in platelet counts during the first 24 hours compared to other blood component therapies, indicating its potential for better hemostatic support.

In patients receiving LTOWB, platelet counts remained stable after the third hour of care, suggesting that LTOWB may effectively sustain platelet levels in critically injured patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cold-stored whole blood and platelet counts in severe acute injury: A comparison of four retrospective cohorts. Asif, M., Hasan, RA., Liu, Z., et al.[2022]

In a study of 348 trauma patients, the use of low-titer group O whole blood (LTOWB) significantly reduced 24-hour mortality compared to component therapy (CT), with rates of 8% for LTOWB versus 19% for CT.

LTOWB not only improved survival, especially in patients experiencing shock or coagulopathy, but also led to a 40% reduction in total blood product use, indicating both safety and efficacy in managing hemorrhaging trauma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doing more with less: low-titer group O whole blood resulted in less total transfusions and an independent association with survival in adults with severe traumatic hemorrhage. Shea, SM., Mihalko, EP., Lu, L., et al.[2023]

References

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

Emergency transfusion with whole blood versus packed red blood cells: A study of 1400 patients. [2023]

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

The use of low-titer group O whole blood is independently associated with improved survival compared to component therapy in adults with severe traumatic hemorrhage. [2021]

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

Adverse events after low titer group O whole blood versus component product transfusion in pediatric trauma patients: A propensity-matched cohort study. [2021]

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

A comparison between leukocyte reduced low titer whole blood vs non-leukocyte reduced low titer whole blood for massive transfusion activation. [2021]

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

Prehospital whole blood reduces early mortality in patients with hemorrhagic shock. [2021]

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

An assessment of the safety, hemostatic efficacy, and clinical impact of low-titer group O whole blood in children and adolescents. [2023]

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

Cold-stored whole blood and platelet counts in severe acute injury: A comparison of four retrospective cohorts. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Doing more with less: low-titer group O whole blood resulted in less total transfusions and an independent association with survival in adults with severe traumatic hemorrhage. [2023]