VPB0996 - FiiRST-2; a prospective, randomized study of clotting factor concentrates versus standard massive hemorrhage protocol in severely bleeding trauma patients

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: Virtual

Co-Author(s)

LD

Luis Da Luz

Department of Surgery
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada

Presenting Author(s)

Jeannie Callum, MD

Director of Transfusion Medicine
Department of Pathology and Molecular Medicine, Kingston Health Sciences Centre, Kingston, Ontario, Canada
Kingston, Ontario, Canada

Co-Author(s)

AB

Andrew Beckett

Department of Surgery
Saint Michael's Hospital
Toronto, Ontario, Canada
HP

Henry Peng

Defence Research and Development
Toronto Research Centre
Toronto, Ontario, Canada
PE

Paul Engels

Department of Surgery
Hamilton General Hospital
Hamilton, Ontario, Canada
NP

Neil Parry

Department of Surgery
London Health Sciences Centre
London, Ontario, Canada
HT

Homer Tien

Department of Surgery
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
AN

Avery Nathens

Department of Surgery
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
JC

Jo Carroll

Department of Anesthesia and Pain Management
University Health Network, Sinai Health System and Women’s College Hospital
Toronto, Ontario, Canada
DG

Deep Grewal

Department of Anesthesia and Pain Management
University Health Network, Sinai Health System and Women’s College Hospital
Toronto, Ontario, Canada
KK

Keyvan Karkouti, MD FRCPC MSc

Chief, Department of Anesthesia and Pain Management
University Health Network; Sinai Health System; Women's College Hospital
Toronto, Ontario, Canada

Background: Acquired fibrinogen deficiency and impaired thrombin generation are major drivers of acute traumatic coagulopathy (ATC), which coupled with bleeding is a leading cause of in-hospital mortality in trauma patients. Early administration of clotting factor concentrates (fibrinogen concentrate [FC], prothrombin complex concentrate [PCC]) may be superior to the current standard of care (SOC); ratio-based plasma resuscitation via a massive hemorrhage protocol (MHP).

Aims: To examine whether early administration of FC+PCC is superior to the current SOC in bleeding trauma patients.

Methods: FiiRST-2 is a randomized, parallel-control, superiority trial with a two-armed, two stage design and adaptive interim analysis performed across 11 Canadian Level I trauma centers (funded by Octapharma). Bleeding trauma patients >16 years old (N=350) will receive FC+PCC (intervention) or 4 units of red blood cells (RBC):plasma (control), plus platelets, until the second MHP pack has been given, MHP is terminated once bleeding has stopped, or 24 h has elapsed from admission (Figure 1). Exclusion criteria include receipt of >2 units RBCs before randomization, >3 h elapsed from injury, catastrophic brain injury, or known bleeding disorders. The primary endpoint is superiority in the number of composite allogeneic blood product units transfused within 24 h after administration. Secondary efficacy endpoints include RBC units transfused within the first 24 h following admission, ventilator-free days, and 28 day all-cause mortality. All adverse and serious adverse events will be assessed through 28 days.

Results: FiiRST-2 has enrolled 60 patients at 4 sites to date. An interim analysis will be performed once 120 patients have completed the study. Completion is expected in Q1 2023.

Conclusion(s): This study will determine whether early use of coagulation factor concentrates (FC+PCC) is superior to the current SOC in bleeding trauma patients, potentially having an impact on clinical practice by improving management and outcomes for this high-risk patient population.