Evaluation of BE1116 in Patients With Traumatic Injury and Acute Major Bleeding to Improve Survival ( TAP Study )

Study Overview
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Brief Summary
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This is a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group, large simple trial to investigate the efficacy and safety of a single intravenous (IV) infusion of BE1116 in subjects who have traumatic injury, with confirmed or suspected acute major bleeding and / or predicted to receive a large volume blood product transfusion.

Official Title
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A Prospective, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Large Simple Trial Evaluating the Use of BE1116 (4-Factor Prothrombin Complex Concentrate [Kcentra® / Beriplex®]) to Improve Survival in Patients With Traumatic Injury and Acute Major Bleeding

Conditions
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Traumatic Injury

Intervention / Treatment
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* Drug: BE1116
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Estimated age ≥ 15 years and weight > 50 kg (110 lbs) Traumatic injury with confirmed or suspected acute major bleeding and/or Revised Assessment of Bleeding and Transfusion (RABT) score ≥ 2 Activation of massive transfusion protocol Exclusion Criteria: Cardiopulmonary resuscitation for ≥ 5 consecutive minutes at any time before enrollment Isolated penetrating or blunt cranial injury, or exposed brain matter Isolated burns estimated to be > 20% total body surface area or suspected inhalational injury Known anticoagulation treatment or a history of a TEE, within the past 3 months.

Ages Eligible for Study
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Minimum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BE1116<br>Administration by IV infusion | Drug: BE1116<br>* 4-Factor Prothrombin Complex administered by intravenous (IV) infusion<br>* Other names: Beriplex®;|
| Placebo Comparator: Placebo<br>Administration by IV infusion | Drug: Placebo<br>* Administered by intravenous (IV) infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in proportion of subjects in all-cause mortality in the BE1116 arm compared with the placebo arm |  | Up to 6 hours after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in proportion of subjects in all-cause in-hospital mortality in the BE1116 arm compared with the placebo arm |  | Up to 24 hours after randomization | 
| Difference in proportion of subjects in all-cause in-hospital mortality in the BE1116 arm compared with the placebo arm |  | Up to 30 days after randomization | 
| Difference in proportion of subjects who undergo surgical or interventional radiological procedures to stop bleeding related to the primary injury in the BE1116 arm compared with the placebo arm |  | Up to 24 hours after randomization | 
| Number and proportion of subjects with serious adverse events (SAEs) considered related to BE1116 or placebo |  | Up to 30 days after randomization | 
| Number and proportion of in-hospital overall and related Thromboembolic events (TEEs) to BE1116 or placebo | Thromboembolic events (TEEs), symptomatic or asymptomatic, and arterial or venous (eg, deep vein thrombosis, pulmonary embolism, ischemic stroke, myocardial infarction) | Up to 30 days after randomization | 
| Number and proportion of subjects with Acute respiratory distress syndrome (ARDS) to BE1116 or placebo |  | Up to 30 days after randomization | 
| Number and proportion of subjects with Multiple organ failure to BE1116 or placebo |  | Up to 30 days after randomization | 
| Number and proportion of subjects with Acute kidney injury (AKI) requiring renal replacement therapy (dialysis, hemofiltration, or hemodiafiltration) to BE1116 or placebo |  | Up to 30 days after randomization |