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Early and empirical high-dose cryoprecipitate for hemorrhage after traumatic injury: The CRYOSTAT-2 randomized clinical trial

Davenport, Ross; Curry, Nicola; Fox, Erin E.; Thomas, Helen; Lucas, Joanne; Evans, Amy; Shanmugaranjan, Shaminie; Sharma, Rupa; Deary, Alison; Edwards, Antoinette; Green, Laura; Wade, Charles E.; Benger, Jonathan R.; Cotton, Bryan A.; Stanworth, Simon J.; Brohi, Karim; Howes, Nathan; Cracolici, Gioacchino; Aylwin, Christopher; Frith, Daniel; Moss, Phil; Jarman, Heather; Cantle, Fleur; Keep, Jeff; Thornley, Jonathan; Downes, Alice; Harrison, Michael; Proctor, Richard; Shelton, Jonathan; Sattout, Abdo; Challen, Kirsty; Horner, Daniel; Carley, Simon; Darwent, Melanie; Kellet, Suzanne; Waller, Bentley; Kong, Robert; Kendall, Jason; Carlton, Edd; Kehoe, Tony; Smith, Jason; Leech, Caroline; Mahmood, Ansar; Hall, Richard; Brooks, Adam; Townend, William; Squires, Justin; Alikhan, Raza; Akhtar, Adeel; Cotton, Cryan; Fox, Erin E; Wade, Charles E; Benger, Jonathan R; Cotton, Bryan A; Stanworth, Simon J

Early and empirical high-dose cryoprecipitate for hemorrhage after traumatic injury: The CRYOSTAT-2 randomized clinical trial Thumbnail


Authors

Ross Davenport

Nicola Curry

Erin E. Fox

Helen Thomas

Joanne Lucas

Amy Evans

Shaminie Shanmugaranjan

Rupa Sharma

Alison Deary

Antoinette Edwards

Laura Green

Charles E. Wade

Jonathan R. Benger

Bryan A. Cotton

Simon J. Stanworth

Karim Brohi

Nathan Howes

Gioacchino Cracolici

Christopher Aylwin

Daniel Frith

Phil Moss

Heather Jarman

Fleur Cantle

Jeff Keep

Jonathan Thornley

Alice Downes

Michael Harrison

Richard Proctor

Jonathan Shelton

Abdo Sattout

Kirsty Challen

Daniel Horner

Simon Carley

Melanie Darwent

Suzanne Kellet

Bentley Waller

Robert Kong

Jason Kendall

Edd Carlton

Tony Kehoe

Jason Smith

Caroline Leech

Ansar Mahmood

Richard Hall

Adam Brooks

William Townend

Justin Squires

Raza Alikhan

Adeel Akhtar

Cryan Cotton

Erin E Fox

Charles E Wade

Jonathan R Benger

Bryan A Cotton

Simon J Stanworth



Abstract

Importance: Critical bleeding is associated with a high mortality rate in patients with trauma. Hemorrhage is exacerbated by a complex derangement of coagulation, including an acute fibrinogen deficiency. Management is fibrinogen replacement with cryoprecipitate transfusions or fibrinogen concentrate, usually administered relatively late during hemorrhage. Objective: To assess whether survival could be improved by administering an early and empirical high dose of cryoprecipitate to all patients with trauma and bleeding that required activation of a major hemorrhage protocol. Design, Setting, and Participants: CRYOSTAT-2 was an interventional, randomized, open-label, parallel-group controlled, international, multicenter study. Patients were enrolled at 26 UK and US major trauma centers from August 2017 to November 2021. Eligible patients were injured adults requiring activation of the hospital's major hemorrhage protocol with evidence of active hemorrhage, systolic blood pressure less than 90 mm Hg at any time, and receiving at least 1 U of a blood component transfusion. Intervention: Patients were randomly assigned (in a 1:1 ratio) to receive standard care, which was the local major hemorrhage protocol (reviewed for guideline adherence), or cryoprecipitate, in which 3 pools of cryoprecipitate (6-g fibrinogen equivalent) were to be administered in addition to standard care within 90 minutes of randomization and 3 hours of injury. Main Outcomes and Measures: The primary outcome was all-cause mortality at 28 days in the intention-to-treat population. Results: Among 1604 eligible patients, 799 were randomized to the cryoprecipitate group and 805 to the standard care group. Missing primary outcome data occurred in 73 patients (principally due to withdrawal of consent) and 1531 (95%) were included in the primary analysis population. The median (IQR) age of participants was 39 (26-55) years, 1251 (79%) were men, median (IQR) Injury Severity Score was 29 (18-43), 36% had penetrating injury, and 33% had systolic blood pressure less than 90 mm Hg at hospital arrival. All-cause 28-day mortality in the intention-to-treat population was 26.1% in the standard care group vs 25.3% in the cryoprecipitate group (odds ratio, 0.96 [95% CI, 0.75-1.23]; P =.74). There was no difference in safety outcomes or incidence of thrombotic events in the standard care vs cryoprecipitate group (12.9% vs 12.7%). Conclusions and Relevance: Among patients with trauma and bleeding who required activation of a major hemorrhage protocol, the addition of early and empirical high-dose cryoprecipitate to standard care did not improve all cause 28-day mortality.

Citation

Davenport, R., Curry, N., Fox, E. E., Thomas, H., Lucas, J., Evans, A., …Stanworth, S. J. (2023). Early and empirical high-dose cryoprecipitate for hemorrhage after traumatic injury: The CRYOSTAT-2 randomized clinical trial. Journal of the American Medical Association, 330(19), 1882-1891. https://doi.org/10.1001/jama.2023.21019

Journal Article Type Article
Acceptance Date Sep 27, 2023
Online Publication Date Oct 12, 2023
Publication Date Nov 21, 2023
Deposit Date Nov 10, 2023
Publicly Available Date Nov 16, 2023
Journal JAMA
Print ISSN 0098-7484
Electronic ISSN 1538-3598
Publisher American Medical Association (AMA)
Peer Reviewed Peer Reviewed
Volume 330
Issue 19
Pages 1882-1891
DOI https://doi.org/10.1001/jama.2023.21019
Public URL https://uwe-repository.worktribe.com/output/11398157

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