Trauma InjuryPhase 3NCT04704869
Early Use of Cryoprecipitate With Major Hemorrhage Protocol (MHP) Activation
A Phase 3 study testing Cryoprecipitate, Red Blood Cells and Plasma in people with Trauma Injury, run by Bryan Cotton at 25 sites in 2 countries.
Trial summary
The purpose of this trial is to compare standard of care (SOC) massive transfusion protocol to SOC massive transfusion protocol plus early use of cryoprecipitate (within 90 minutes of emergency department arrival). Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Trauma Injury
- What is being tested?
- Cryoprecipitate, Red Blood Cells and Plasma
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,604 participants
- Where
- 25 sitesin 2 countries
- Study dates
- Jan 2017to 1 Nov 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- The patient is judged to be an adult (according to local practice, e.g. 16 years or older in UK) and has sustained severe traumatic injury. In the event the age is unknown, estimated body weight ≥50 kg.
- The patient is deemed by the attending clinician to have on-going active hemorrhage AND REQUIRES Activation of the local major hemorrhage protocol for management of severe blood loss AND HAS STARTED or HAS RECEIVED at least one unit of any blood component
Who cannot join
- The patient has been transferred from another hospital
- The trauma team leader deems the injuries incompatible with life
- More than 3 hours have elapsed from the time of injury
- Prisoner (as defined as someone admitted from a correctional facility)
- Known "Do Not Resuscitate" orders
- Enrolled in a concurrent ongoing interventional, randomized clinical trial
Show all 9Show fewer
- Patients who wear "opt out" bracelet for study
- Obvious pregnancy
- Severely burned
Trial locations and contacts
25 sites in 2 countries.
25 sites in 2 countries
United Kingdom24 sites
Queen Elizabeth Hospital
Birmingham, B15 2TH
Royal Sussex County Hospital
Brighton, BN2N 5BE
Southmead Hospital
Bristol, BS10 5NB
Addenbrooke's Hospital
Cambridge, CB2 0QQ
University Hospital of Wales
Cardiff, CF14 4XW
University Hospital of Coventry and Warwickshire
Coventry, CV2 2DX
Hull Royal Infirmary
Hull, HU3 2JZ
Leeds General Infirmary
Leeds, LS1 3EX
University Hospital Aintree
Liverpool, L9 7AL
Royal London Hospital
London, E1 1BB
King's College Hospital
London, SE5 9RS
St. George's Hospital
London, SW17 0QT
St. Mary's Hospital
London, W2 1NY
Manchester Royal Infirmary
Manchester, M13 9WL
Salford Royal Hospital
Manchester, M6 8HD
James Cook University Hospital
Middlesbrough, TS4 3BW
Royal Victoria Infirmary
Newcastle upon Tyne, NE1 4LP
Queens Medical Centre
Nottingham, NG7 2UH
John Radcliffe Hospital
Oxford, OX3 9UD
Derriford Hospital
Plymouth, PL6 8DH
Royal Preston Hospital
Preston, PR2 9HT
Northern General Hospital
Sheffield, S5 7AU
University Hospital Southampton
Southampton, SO16 6YD
University Hospital of North Staffordshire
Stoke-on-Trent, ST4 6QG
United States1 site
The University of Texas Health Science Center at Houston
Houston, Texas, 77030
About this study
Official title: A Multi-center, Randomized, Controlled Trial Evaluating the Effects of Early High-Dose Cryoprecipitate in Adult Patients With Major Trauma Hemorrhage Requiring Major Hemorrhage Protocol (MHP) Activation
The purpose of this trial is to compare standard of care (SOC) massive transfusion protocol to SOC massive transfusion protocol plus early use of cryoprecipitate (within 90 minutes of emergency department arrival).
- Conditions
- Trauma Injury
- Being tested
- Cryoprecipitate, Red Blood Cells, Plasma, Platelets, Whole Blood
- Medical subject headings
- Accidental Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CryoprecipitateBiological
Cryoprecipitate is a blood product high in fibrinogen. The Cryoprecipitate will be given with 90 minutes of emergency department arrival. Cryoprecipitate dose will be 3 pools (equivalent to 15 single units).
Red Blood CellsBiological
Also called RBCs
RBCs are utilized as part of the Massive Transfusion protocol for hemorrhage control.
PlasmaBiological
Plasma is utilized as part of the Massive Transfusion protocol for hemorrhage control.
PlateletsBiological
Platelets are utilized as part of the Massive Transfusion protocol for hemorrhage control.
Whole BloodBiological
Whole Blood is utilized as part of the Massive Transfusion protocol for hemorrhage control.
| Study group | Role | What they receive |
|---|---|---|
| Early Cryoprecipitate + Massive Transfusion Protocol (RBCs, Plasma, Platelets, Whole Blood) | Experimental | Cryoprecipitate will be given in addition to the standard of care massive transfusion protocol products, which include red blood cells, plasma, platelets and whole blood. The Cryoprecipitate will be given with 90 minutes of emergency department arrival. Cryoprecipitate dose will be 3 pools (equivalent to 15 single units). Receives: Biological: Cryoprecipitate; Biological: Red Blood Cells; Biological: Plasma; Biological: Platelets; Biological: Whole Blood |
| Massive Transfusion Protocol (RBCs, Plasma, Platelets, Whole Blood) | Active comparator | Only standard of care massive transfusion protocol products will be given, including red blood cells, plasma, platelets, and whole blood. Receives: Biological: Red Blood Cells; Biological: Plasma; Biological: Platelets; Biological: Whole Blood |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Mortality From Any Cause
Mortality from any cause
Measured: 28 days after emergency department (ED) admission
Secondary outcomes (18)
All Cause Mortality at 6 Hours
Mortality from any cause
Measured: 6 hours after ED admission
All Cause Mortality at 24 Hours
Mortality from any cause
Measured: 24 hours after ED admission
All Cause Mortality at 6 Months
Mortality from any cause. All cause mortality at 6 months is presented as a Kaplan-Meier estimated.
Measured: 6 months after ED admission
All Cause Mortality at 12 Months
Mortality from any cause. All cause mortality at 6 months is presented as a Kaplan-Meier estimated.
Measured: 12 months after ED admission
Death From Bleeding at 6 Hours
Death related to exsanguination
Measured: 6 hours after ED admission
Death From Bleeding at 24 Hours
Death related to exsanguination
Measured: 24 hours after ED admission
Transfusion Requirements (Number of Units of Red Blood Cells (RBCs))
Number of units of RBCs
Measured: from time of pre-hospital care to 24 hours after ED admission, an average of 30 hours
Transfusion Requirements (Number of Units of Plasma)
Number of units of plasma
Measured: from time of pre-hospital care to 24 hours after ED admission, an average of 30 hours
Transfusion Requirements (Number of Units of Platelets)
Number of units of platelets
Measured: from time of pre-hospital care to 24 hours after ED admission, an average of 30 hours
Transfusion Requirements (Number of Units of Cryoprecipitate)
Number of units of cryoprecipitate
Measured: from time of pre-hospital care to 24 hours after ED admission, an average of 30 hours
Destination of Participant at Time of Discharge From Hospital
Destination of participant at time of discharge from hospital
Measured: at the time of discharge from hospital, about 11-27 days after admission
Quality of Life as Assessed by EuroQol-5 Dimension-5 Level (EQ5D-5L)
The 5-level EQ-5D version (EQ-5D-5L) score range was -0.148 (worst health state) to 0.949 (best health state). A higher score indicating a better health state.
Measured: Day of hospital discharge or 28 days after ED admission (whichever comes first)
Quality of Life as Assessed by the Glasgow Outcome Score
The Glasgow Outcome Score ranges from 1 to 5, with a higher score indicating a better outcome:
- Death - Severe injury or death without recovery of consciousness
- Persistent vegetative state - Severe damage with prolonged state of unresponsiveness and a lack of higher mental functions
- Severe disability - Severe injury with permanent need for help with daily living
- Moderate disability - No need for assistance in everyday life, employment is possible but may require special equipment
- Low disability - Light damage with minor neurological and psychological deficits
Measured: Day of hospital discharge or 28 days after ED admission (whichever comes first)
Quality of Life as Assessed by EuroQol-5 Dimension-5 Level (EQ5D-5L)
The 5-level EQ-5D version (EQ-5D-5L) score range was -0.148 (worst health state) to 0.949 (best health state). A higher score indicating a better health state.
Measured: 6 months after ED admission
Quality of Life as Assessed by the Glasgow Outcome Score
The Glasgow Outcome Score ranges from 1 to 5, with a higher score indicating a better outcome:
- Death - Severe injury or death without recovery of consciousness
- Persistent vegetative state - Severe damage with prolonged state of unresponsiveness and a lack of higher mental functions
- Severe disability - Severe injury with permanent need for help with daily living
- Moderate disability - No need for assistance in everyday life, employment is possible but may require special equipment
- Low disability - Light damage with minor neurological and psychological deficits
Measured: 6 months after ED admission
Hospital Resource Use as Assessed by Number of Ventilator Days
Number of ventilator days during hospitalization
Measured: Day of hospital discharge or 28 days after ED admission (whichever comes first)
Hospital Resource Use as Assessed by Number of Intensive Care Unit (ICU) Days
Number of ICU days during hospitalization
Measured: Day of hospital discharge or 28 days after ED admission (whichever comes first)
Hospital Resource Use as Assessed by Number of Hospital Days
Total number of hospital days
Measured: Day of hospital discharge or 28 days after ED admission (whichever comes first)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2021
- Study startJan 2017
- Primary completion1 Dec 2021
- Study completion1 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Trauma InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,604 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bryan Cotton
- Sponsor type
- University, hospital or other
- Collaborators
- Queen Mary University of London, NHS Blood and Transplant
- Responsible party
- Sponsor-investigator, Bryan Cotton, The University of Texas Health Science Center, Houston
- Investigators
- Bryan A Cotton, MD, Principal investigator, The University of Texas Health Science Center, Houston
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04704869
- Sponsor's protocol ID
- HSC-MS-19-0272
- Other IDs
- ISRCTN14998314
- Status last verified
- Dec 2024
- First submitted
- 6 Jan 2021
- Last updated
- 14 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Davenport R, Curry N, Fox EE, Thomas H, Lucas J, Evans A, Shanmugaranjan S, Sharma R, Deary A, Edwards A, Green L, Wade CE, Benger JR, Cotton BA, Stanworth SJ, Brohi K; CRYOSTAT-2 Principal Investigators. Early and Empirical High-Dose Cryoprecipitate for Hemorrhage After Traumatic Injury: The CRYOSTAT-2 Randomized Clinical Trial. JAMA. 2023 Nov 21;330(19):1882-1891. doi: 10.1001/jama.2023.21019.
PubMed 37824155
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Randomized, Controlled Trial Evaluating the Effects of Early High-Dose Cryoprecipitate in Adult Patients With Major Trauma Hemorrhage Requiring Major Hemorrhage Protocol (MHP) Activation
- ClinicalTrials.gov ID
- NCT04704869
- Acronym / sponsor ID
- HSC-MS-19-0272
- Conditions
- Trauma Injury
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,604 participants (actual)
- Lead sponsor
- Bryan CottonUniversity, hospital or other
- Collaborators
- Queen Mary University of London, NHS Blood and Transplant
- Study start
- Jan 2017 (actual)
- Primary completion
- 1 Dec 2021 (actual)
- Study completion
- 1 Nov 2022 (actual)
- First posted
- 12 Jan 2021 (actual)
- Results
- Posted 21 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this trial is to compare standard of care (SOC) massive transfusion protocol to SOC massive transfusion protocol plus early use of cryoprecipitate (within 90 minutes of emergency department arrival).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Early Cryoprecipitate + Massive Transfusion Protocol (RBCs, Plasma, Platelets, Whole Blood) | Experimental | Biological: Cryoprecipitate, Biological: Red Blood Cells, Biological: Plasma, Biological: Platelets, Biological: Whole BloodCryoprecipitate will be given in addition to the standard of care massive transfusion protocol products, which include red blood cells, plasma, platelets and whole blood. The Cryoprecipitate will be given with 90 minutes of emergency department arrival. Cryoprecipitate dose will be 3 pools (equivalent to 15 single units). |
| Massive Transfusion Protocol (RBCs, Plasma, Platelets, Whole Blood) | Active comparator | Biological: Red Blood Cells, Biological: Plasma, Biological: Platelets, Biological: Whole BloodOnly standard of care massive transfusion protocol products will be given, including red blood cells, plasma, platelets, and whole blood. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- The patient is judged to be an adult (according to local practice, e.g. 16 years or older in UK) and has sustained severe traumatic injury. In the event the age is unknown, estimated body weight ≥50 kg.
- The patient is deemed by the attending clinician to have on-going active hemorrhage AND REQUIRES Activation of the local major hemorrhage protocol for management of severe blood loss AND HAS STARTED or HAS RECEIVED at least one unit of any blood component
Key exclusion criteria (9 listed)
- The patient has been transferred from another hospital
- The trauma team leader deems the injuries incompatible with life
- More than 3 hours have elapsed from the time of injury
- Prisoner (as defined as someone admitted from a correctional facility)
- Known "Do Not Resuscitate" orders
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CryoprecipitateCryoprecipitate is a blood product high in fibrinogen. The Cryoprecipitate will be given with 90 minutes of emergency department arrival. Cryoprecipitate dose will be 3 pools (equivalent to 15 single units). | Biological | Early Cryoprecipitate + Massive Transfusion Protocol (RBCs, Plasma, Platelets, Whole Blood) |
| Red Blood CellsAlso: RBCsRBCs are utilized as part of the Massive Transfusion protocol for hemorrhage control. | Biological | Early Cryoprecipitate + Massive Transfusion Protocol (RBCs, Plasma, Platelets, Whole Blood), Massive Transfusion Protocol (RBCs, Plasma, Platelets, Whole Blood) |
| PlasmaPlasma is utilized as part of the Massive Transfusion protocol for hemorrhage control. | Biological | Early Cryoprecipitate + Massive Transfusion Protocol (RBCs, Plasma, Platelets, Whole Blood), Massive Transfusion Protocol (RBCs, Plasma, Platelets, Whole Blood) |
| PlateletsPlatelets are utilized as part of the Massive Transfusion protocol for hemorrhage control. | Biological | Early Cryoprecipitate + Massive Transfusion Protocol (RBCs, Plasma, Platelets, Whole Blood), Massive Transfusion Protocol (RBCs, Plasma, Platelets, Whole Blood) |
| Whole BloodWhole Blood is utilized as part of the Massive Transfusion protocol for hemorrhage control. | Biological | Early Cryoprecipitate + Massive Transfusion Protocol (RBCs, Plasma, Platelets, Whole Blood), Massive Transfusion Protocol (RBCs, Plasma, Platelets, Whole Blood) |
Primary outcome
Number of Participants With Mortality From Any Cause
Time frame: 28 days after emergency department (ED) admission
Mortality from any cause
18 secondary outcomes
All Cause Mortality at 6 Hours
Time frame: 6 hours after ED admission
All Cause Mortality at 24 Hours
Time frame: 24 hours after ED admission
All Cause Mortality at 6 Months
Time frame: 6 months after ED admission
All Cause Mortality at 12 Months
Time frame: 12 months after ED admission
Death From Bleeding at 6 Hours
Time frame: 6 hours after ED admission
Death From Bleeding at 24 Hours
Time frame: 24 hours after ED admission
Transfusion Requirements (Number of Units of Red Blood Cells (RBCs))
Time frame: from time of pre-hospital care to 24 hours after ED admission, an average of 30 hours
Transfusion Requirements (Number of Units of Plasma)
Time frame: from time of pre-hospital care to 24 hours after ED admission, an average of 30 hours
Transfusion Requirements (Number of Units of Platelets)
Time frame: from time of pre-hospital care to 24 hours after ED admission, an average of 30 hours
Transfusion Requirements (Number of Units of Cryoprecipitate)
Time frame: from time of pre-hospital care to 24 hours after ED admission, an average of 30 hours
Destination of Participant at Time of Discharge From Hospital
Time frame: at the time of discharge from hospital, about 11-27 days after admission
Quality of Life as Assessed by EuroQol-5 Dimension-5 Level (EQ5D-5L)
Time frame: Day of hospital discharge or 28 days after ED admission (whichever comes first)
Quality of Life as Assessed by the Glasgow Outcome Score
Time frame: Day of hospital discharge or 28 days after ED admission (whichever comes first)
Quality of Life as Assessed by EuroQol-5 Dimension-5 Level (EQ5D-5L)
Time frame: 6 months after ED admission
Quality of Life as Assessed by the Glasgow Outcome Score
Time frame: 6 months after ED admission
Hospital Resource Use as Assessed by Number of Ventilator Days
Time frame: Day of hospital discharge or 28 days after ED admission (whichever comes first)
Hospital Resource Use as Assessed by Number of Intensive Care Unit (ICU) Days
Time frame: Day of hospital discharge or 28 days after ED admission (whichever comes first)
Hospital Resource Use as Assessed by Number of Hospital Days
Time frame: Day of hospital discharge or 28 days after ED admission (whichever comes first)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 37824155Davenport R, Curry N, Fox EE, Thomas H, Lucas J, Evans A, Shanmugaranjan S, Sharma R, Deary A, Edwards A, Green L, Wade CE, Benger JR, Cotton BA, Stanworth SJ, Brohi K; CRYOSTAT-2 Principal Investigators. Early and Empirical High-Dose Cryoprecipitate for Hemorrhage After Traumatic Injury: The CRYOSTAT-2 Randomized Clinical Trial. JAMA. 2023 Nov 21;330(19):1882-1891. doi: 10.1001/jama.2023.21019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bryan A Cotton, MD principal investigator
The University of Texas Health Science Center, Houston
25 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cryoprecipitate, Red Blood Cells and Plasma in people with Trauma Injury, run by Bryan Cotton at 25 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United Kingdom, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Mortality From Any Cause (time frame: 28 days after emergency department (ED) admission). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04704869, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2025.