Low Titer Whole Blood for Hemorrhagic Shock

(TOWAR Trial)

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether low titer whole blood is better and safer than usual blood transfusion methods for individuals at risk of hemorrhagic shock. Hemorrhagic shock occurs when significant blood loss prevents the body from getting enough oxygen, leading to serious complications. The trial compares whole blood transfusions with standard care to determine which is more effective, particularly before hospital arrival. Potential participants include those with very low blood pressure and a fast heart rate due to injury, being transported to a participating center. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that Low Titer Whole Blood (LTOWB) transfusions are generally safe for individuals with serious injuries. Studies have found that this type of blood transfusion is effective and well-tolerated by both group O and non-group O blood types. Previous research suggests that using LTOWB in emergencies can be done safely and might even aid in blood clotting.

One study found that using LTOWB for treating trauma did not cause more complications or increase death rates. In fact, it was linked to better survival rates within the first 24 hours after treatment.

Overall, these findings suggest that LTOWB is a promising and safe option for treating individuals at risk of significant blood loss. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard care for hemorrhagic shock, which typically involves prehospital crystalloid infusion or blood component transfusion, Low Titer Whole Blood is administered as whole blood units. This approach is unique because whole blood provides a more comprehensive resuscitation option, containing red cells, plasma, and platelets, all in one package. Researchers are excited about this treatment because it can be initiated quickly in the prehospital setting and may lead to more efficient management of blood loss, potentially improving survival outcomes for patients experiencing severe bleeding.

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

Studies have shown that low titer whole blood (LTOWB) is a promising treatment for severe blood loss, particularly in trauma cases. Research indicates that LTOWB can improve survival rates within the first 24 hours for patients experiencing heavy bleeding. It offers benefits such as quicker administration and balanced blood components, which are crucial in emergencies. In this trial, some participants will receive LTOWB, while others will receive standard care, including prehospital crystalloid infusion or blood component transfusion. Patients receiving LTOWB have demonstrated similar outcomes to those receiving traditional blood therapy. This suggests that LTOWB is not only effective but also safe for many patients, including those who are not blood type O. ^{1 2 4 5 6}

Who Is on the Research Team?

Jason Sperry, MD, MPH

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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 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]

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. 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 ...

4. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-025-08971-y

Trauma resuscitation with Low-Titer Group O Whole Blood Or ... A recent study has shown reduced “flow time” from making the decision to transfuse, to completion of transfusion, as well as decreased hands-on ...

5. jamanetwork.com jamanetwork.com/journals/jamasurgery/fullarticle/2814272

Timing to First Whole Blood Transfusion and Survival ... Injured recipients of low-titer group O whole blood have similar clinical outcomes compared to recipients of conventional component therapy ...

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

PREHOSPTIAL LOW TITER GROUP O WHOLE BLOOD IS ... Prehospital through in-hospital LTOWB resuscitation is safe and may be associated with hemostatic benefits. A large-scale clinical trial is feasible with ...