Contributions of authors
Nicola Curry (https://orcid.org/0000-0002-3849-0688) (Consultant Haematologist, Co-Investigator) was involved in the design, conduct, analysis and reporting phases of the study.
Ross Davenport (https://orcid.org/0000-0002-8593-6582) (Consultant Trauma and Vascular Surgeon, Co-Investigator) was involved in the design, conduct, analysis and reporting phases of the study.
Helen Thomas (https://orcid.org/0000-0002-7017-7739) (Head of Clinical Trial Statistics) was involved in the design, conduct, analysis and reporting phases of the study.
Erin Fox (https://orcid.org/0000-0002-8843-5054) (Study Management in US) was involved in the conduct phase of the study.
Joanne Lucas (https://orcid.org/0000-0002-3390-9654) (Clinical Trial Manager) was involved in the conduct and reporting phases of the study.
Amy Evans (https://orcid.org/0000-0002-6664-9342) (Clinical Trial Manager) was involved in the conduct and reporting phases of the study.
Efthalia Massou (https://orcid.org/0000-0003-0488-482X) (Research Associate in Statistics) was involved in the analysis and reporting phases of the study.
Rupa Sharma (https://orcid.org/0009-0000-5414-0859) (Clinical Data Manager) was involved in the conduct phase of the study.
Shaminie Shanmugaranjan (https://orcid.org/0009-0009-2091-4014) (Statistician) was involved in the analysis and reporting phases of the study.
Claire Rourke (https://orcid.org/0000-0002-7631-9275) (Clinical Operations Manager) was involved in the design, conduct and reporting phase of the study.
Alice Newton (https://orcid.org/0009-0009-1437-7953) (Statistician) was involved in the conduct and analysis phases of the study.
Alison Deary (https://orcid.org/0000-0001-8351-4186) (Head of Clinical Operations) was involved in the design and conduct phases of the study.
Nikki Dallas (https://orcid.org/0009-0009-9604-027X) (Data Management Support Officer) was involved in the conduct phase of the study.
Chloe Fitzpatrick-Creamer (https://orcid.org/0009-0000-8064-6108) (Clinical Trial Administrator) was involved in the conduct phase of the study.
Jeanette M Podbielski (https://orcid.org/0000-0003-4053-8553) (Study Management in US) was involved in the conduct phase of the study.
Charles E Wade (https://orcid.org/0000-0003-0055-5885) (Trauma Surgeon) was involved in the conduct phase of the study.
Antoinette Edwards (https://orcid.org/0000-0003-1427-0725) (Executive Director, TARN) was involved in the design and conduct of the study.
Jonathan Benger (https://orcid.org/0000-0001-6131-0916) (Professor of Emergency Care, Co-investigator) was involved in the design, conduct and reporting phases of the study.
Stephen Morris (https://orcid.org/0000-0002-5828-3563) (Professor of Health Services Research) was involved in the design, conduct, analysis and reporting phases of the study.
Bryan A Cotton (https://orcid.org/0000-0003-4184-6742) (Trauma Surgeon) was involved in the conduct phase of the study.
James Piercy (https://orcid.org/0000-0003-4891-7259) (expert lay representative) was involved in the design, conduct and reporting phases of the study.
Laura Green (https://orcid.org/0000-0003-4063-9768) (Consultant Haematologist) Co-Investigator, was involved in the design, conduct and reporting phases of the study.
Karim Brohi (https://orcid.org/0000-0003-0643-8866) (Professor of Trauma Sciences, Chief Investigator) was involved in the design, conduct, analysis and reporting phases of the study.
Simon Stanworth (https://orcid.org/0000-0002-7414-4950) (Consultant Haematologist, Co-Chief Investigator) was involved in the design, conduct, analysis and reporting phases of the study.
Acknowledgements
We would like to acknowledge and thank the significant contribution made by our oversight committees in their oversight and governance of the trial.
Trial Steering Committee
Professor Beverley Hunt OBE (Chairperson), Professor Jason L Sperry (Clinical Specialist), Dr Alastair Nimmo (Clinical Specialist), James Piercy (Patient Representative) and Kathryn Orchard (Patient Representative).
Data Monitoring Committee
Professor Timothy Coats (Chairperson), Professor Gavin Murphy (Clinical Specialist) and Professor Paul White (Independent Statistician).
We would like to acknowledge the contribution of Claire Foley (NHS Blood and Transplant Clinical Trials Unit) in the design and conduct phases of the study.
Participating sites
We would like to thank the principal investigators and transfusion leads at the participating hospitals for supporting the trial. We also wish to thank all the research teams at sites, without whom the trial would not have been possible.
Cambridge University Hospital: Dr Nathan Howes, Dr Gioacchino Cracolici, Katherine Philpott and Claire Newsam.
St Mary’s Hospital: Mr Dan Firth, Mr Christopher Aylwin and Dr Feteha Chowdhury.
St George’s Hospital: Dr Phil Moss, Professor Heather Jarman and Steve Wilshire.
Royal London Hospital: Dr Ross Davenport and Dr Laura Green.
King’s College London: Dr Fleur Cantle, Dr Jeff Keep and Kenneth Amenyah.
Leeds General Infirmary: Dr Jonathan Thornley, Dr Michael Harrison, Dr Alice Downes, Dr Marina Karakantza and Gulraiz Hussain.
James Cook University Hospital: Dr Richard Procter and Chris Elliott.
Royal Victoria Infirmary: Dr Jonathan Shelton and Gemma Smithson.
Aintree University Hospital: Dr Abdo Sattout, Rebecca Wright and Jan Gorry.
Royal Preston Hospital: Dr Kirsty Challen and Alan Noyon.
Salford Royal Hospital: Dr Dan Horner and Lydia Baxter.
Manchester Royal Infirmary: Professor Simon Carley, Dr Kate Pendry and Thomas Trimble.
John Radcliffe Hospital: Dr Melanie Darwent and Julie Staves.
Southampton General Hospital: Dr Suzanne Kellett, Dr Bentley Waller and Kerry Dowling.
Royal Sussex County Hospital: Dr Robert Kong and Julie Cole.
Southmead Hospital: Dr Jason Kendall, Professor Edd Carlton and Tim Wreford-Bush.
Derriford Hospital: Dr Tony Kehoe, Professor Jason Smith, Martin Binney and Caroline Lowe.
Queen Elizabeth Hospital: Dr Ansar Mahmood and Dr Suzanne Morton.
University Hospital of Coventry and Warwickshire: Dr Caroline Leech, Dr Maria Mushkbar and Julie Northcote.
University Hospital of North Staffordshire: Dr Richard Hall, Rebecca Sivers and Jane Graham.
Queen’s Medical Centre: Dr Adam Brooks and Dr Cherry Chang.
Hull Royal Infirmary: Dr William Townend, Robert Elshaw and Mandy Bryan.
Northern General Hospital: Dr Justin Squires and Brian Taylor.
University Hospital of Wales: Dr Raza Alikhan.
Royal Victoria Hospital, Belfast: Dr Adeel Akhtar and Stephen Kane.
University of Texas Healthcare Center at Houston: Dr Bryan A Cotton, Dr Erin E Fox, Janette Podbielski and Charles Wade.
We would like to recognise the team at the University of Texas Healthcare Center at Houston team (Erin Fox, Bryan Cotton, Charles Wade and Janette Podbielski) for preparing and co-ordinating the submission to the US Food and Drug Administration to allow the trial to open in the USA.
We would especially like to thank the patients and their families for participating in this trial.
Patient data statement
This work uses data provided by patients and collected by the NHS as part of their care and support. Using patient data is vital to improve health and care for everyone. There is huge potential to make better use of information from people’s patient records, to understand more about disease, develop new treatments, monitor safety and plan NHS services. Patient data should be kept safe and secure, to protect everyone’s privacy, and it’s important that there are safeguards to make sure that they are stored and used responsibly. Everyone should be able to find out about how patient data are used. #datasaveslives You can find out more about the background to this citation here: https://understandingpatientdata.org.uk/data-citation.
Data-sharing statement
All data requests should be submitted to the corresponding author for consideration. Access to anonymised data may be granted following review.
Ethics statement
The South Central – Oxford C Research Ethics Committee reviewed the protocol and supporting documents for the CRYOSTAT-2 trial and provided a favourable ethics opinion on 26 May 2017 (Research Ethics Committee reference 17/SC/0164).
Information governance statement
Queen Mary University of London and NHS Blood and Transplant are committed to handling all personal information in line with the UK Data Protection Act (2018) and the General Data Protection Regulation (EU GDPR) 2016/679.
Under the Data Protection legislation, Queen Mary University of London and NHS Blood and Transplant are joint Data Controllers; NHS Blood and Transplant is the Data Processor and process personal data in accordance with the Data Controllers’ instructions. You can find out more about how they handle personal data, including how to exercise your individual rights and the contact details for the Data Protection Officer, here: www.nhsbt.nhs.uk/privacy/; www.qmul.ac.uk/privacy/.
Disclosure of interests
Full disclosure of interests: Completed ICMJE forms for all authors, including all related interests, are available in the toolkit on the NIHR Journals Library report publication page at https://doi.org/10.3310/JYTR6938.
Primary conflicts of interest: Karim Brohi and Simon Stanworth report grants from the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme during the conduct of the study. Karim Brohi also reports grants from Barts Charity (London, UK). Simon Stanworth is employed by NHS Blood and Transplant (NHSBT), which manufactures cryoprecipitate. Ross Davenport reports membership of a Data Safety Monitoring Committee and grants from HemoSonics (Durham, NC, USA), Werfen (Barcelona, Spain), Barts Charity and NHSBT. Stephen Morris reports former membership of the NIHR Health and Social Care Delivery Research (HS&DR) Commissioning Board (June 2014–March 2016), the NIHR HS&DR Evidence Synthesis Sub-Board (May 2016–October 2016), the NIHR Public Health Research Research Funding Board (June 2011–June 2017), the NIHR HS&DR Funding Committee (June 2014–June 2019) and NIHR HS&DR Sub-Committee Unmet Need (November 2019). Stephen Morris and Efthalia Massou received funding for the present manuscript. Nicola Curry reports participation in an advisory board (Octapharma) and being part of the International Society on Thrombosis and Haemonstatis Scientific Subcommittee for Perioperative Care. Charles E Wade reported receiving grants from Barts Charity during the conduct of the study and holding stock in Decisio Health (Houston, TX, USA), receiving grants from Athersys (Cleveland OH, USA) and Grifols (Barcelona, Spain), and receiving personal fees from Cellphire (Rockville, MD, USA) outside the submitted work. Bryan A Cotton reported receiving grants from Barts Charity during the conduct of the study and personal fees from Cerus (Concord, CA, USA) outside the submitted work. Erin Fox reports receiving grants or contracts from Queen Mary University of London, the US Department of Defense, the US National Institutes of Health and Grifols. Jeanette M Podbielski received funding from Queen Mary University of London for the current manuscript and had contracts with the US Department of Health and Human Services, the US National Institutes of Health and Grifols. They also report consulting fees from Arsenal Medical (Waltham MA, USA), Avania Clinical (Boston, MA, USA), JSL Innovations LLC (Houston, TX, USA) and CCJ Medical (Davidson, NC, USA). Laura Green received an honorarium from the University of Oslo and received support from the Haematology Society of Australia and New Zealand for attendance at its annual meeting (2022). James Piercy received payments from Cambridge Biological Research Centre and NIHR Brain Injury MedTech Co-operative and reports being a trustee of the UK Brain Injury Forum.
Publications
Marsden M, Benger J, Brohi K, Curry N, Foley C, Green L, et al.; CRYOSTAT-2 investigators. Coagulopathy, cryoprecipitate and CRYOSTAT-2: realising the potential of a nationwide trauma system for a national clinical trial. Br J Anaesth 2019;122:164–9. https://doi.org/10.1016/j.bja.2018.10.055
Curry N, Davenport R, Lucas J, Deary A, Benger J, Edwards A, et al. The CRYOSTAT2 trial: the rationale and study protocol for a multi-Centre, randomised, controlled trial evaluating the effects of early high-dose cryoprecipitate in adult patients with major trauma haemorrhage requiring major haemorrhage protocol activation. Transfus Med 2023;33:123–31. https://doi.org/10.1111/tme.12932
Davenport R, Curry N, Fox EE, Thomas H, Lucas J, Evans A, et al. Early and empirical high-dose cryoprecipitate for hemorrhage after traumatic injury: the CRYOSTAT-2 randomized clinical trial. JAMA 2023;330:1882–91. https://doi.org/10.1001/jama.2023.21019
Disclaimers
This article presents independent research funded by the National Institute for Health and Care Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, the HTA programme or the Department of Health and Social Care. If there are verbatim quotations included in this publication the views and opinions expressed by the interviewees are those of the interviewees and do not necessarily reflect those of the authors, those of the NHS, the NIHR, the HTA programme or the Department of Health and Social Care.