Evidence-Based and Clinically Relevant Outcomes for Hemorrhage Control Trauma Trials

Area of Science:

• Hematology and clinical trials
• Hemostasis and thrombosis research
• Medical regulatory science

Background:

• Standardized primary outcomes are crucial for hemostasis research, improving trial interpretation and clinical practice translation.
• Alignment among funders, investigators, clinicians, and regulators is supported by consistent outcome measures.
• Addressing clinical and regulatory challenges in bleeding patient trials necessitates consensus-based recommendations.

Purpose of the Study:

• To develop consensus-based recommendations for primary clinical outcomes in pivotal trials for patients experiencing significant bleeding.
• To establish optimal primary endpoints across six distinct bleeding categories: traumatic injury, intracranial hemorrhage, cardiac surgery, gastrointestinal hemorrhage, inherited bleeding disorders, and hypoproliferative thrombocytopenia.

Main Methods:

• Convening an international expert panel by the National Heart Lung and Blood Institute and the U.S. Department of Defense.
• A dedicated trauma working group engaged in year-long discussions, including biweekly calls and an in-person meeting.
• Selection criteria for primary outcomes prioritized patient-centeredness, treatment effect sensitivity, biologic plausibility, feasibility, and applicability.

Main Results:

• For patients with hemorrhagic shock, particularly truncal hemorrhage, 3- to 6-hour all-cause mortality is the recommended primary outcome.
• This mortality endpoint aligns with the physiology of hemorrhagic death and mitigates bias from competing risks.
• Emphasis is placed on considering injury and treatment timing, alongside comprehensive safety outcome assessments.

Conclusions:

• The study provides consensus-based recommendations for primary endpoints in significant bleeding trials.
• A standardized primary outcome, such as 3- to 6-hour mortality for hemorrhagic shock, will enhance hemostasis research.
• These recommendations aim to improve the conduct, interpretation, and clinical application of hemostasis research.