Early Use of Cryoprecipitate With Major Hemorrhage Protocol (MHP) Activation

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).

Study Overview

• Status: Completed
• Conditions: Trauma Injury
• Intervention / Treatment: Biological: Cryoprecipitate; Biological: Red Blood Cells; Biological: Plasma; Biological: Platelets; Biological: Whole Blood

• Study Type: Interventional
• Enrollment (Actual): 1604
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Queen Elizabeth Hospital
  • Brighton, United Kingdom, BN2N 5BE
    • Royal Sussex County Hospital
  • Bristol, United Kingdom, BS10 5NB
    • Southmead Hospital
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke's Hospital
  • Cardiff, United Kingdom, CF14 4XW
    • University Hospital of Wales
  • Coventry, United Kingdom, CV2 2DX
    • University Hospital of Coventry and Warwickshire
  • Hull, United Kingdom, HU3 2JZ
    • Hull Royal Infirmary
  • Leeds, United Kingdom, LS1 3EX
    • Leeds General Infirmary
  • Liverpool, United Kingdom, L9 7AL
    • University Hospital Aintree
  • London, United Kingdom, SE5 9RS
    • King's College Hospital
  • London, United Kingdom, E1 1BB
    • Royal London Hospital
  • London, United Kingdom, W2 1NY
    • St. Mary's Hospital
  • London, United Kingdom, SW17 0QT
    • St. George's Hospital
  • Manchester, United Kingdom, M13 9WL
    • Manchester Royal Infirmary
  • Manchester, United Kingdom, M6 8HD
    • Salford Royal Hospital
  • Middlesbrough, United Kingdom, TS4 3BW
    • James Cook University Hospital
  • Newcastle Upon Tyne, United Kingdom, NE1 4LP
    • Royal Victoria Infirmary
  • Nottingham, United Kingdom, NG7 2UH
    • Queens Medical Centre
  • Oxford, United Kingdom, OX3 9UD
    • John Radcliffe Hospital
  • Plymouth, United Kingdom, PL6 8DH
    • Derriford Hospital
  • Preston, United Kingdom, PR2 9HT
    • Royal Preston Hospital
  • Sheffield, United Kingdom, S5 7AU
    • Northern General Hospital
  • Southampton, United Kingdom, SO16 6YD
    • University Hospital Southampton
  • Stoke-on-Trent, United Kingdom, ST4 6QG
    • University Hospital of North Staffordshire
• United States
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• Patients who wear "opt out" bracelet for study
• Obvious pregnancy
• Severely burned

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early Cryoprecipitate + Massive Transfusion Protocol (RBCs, Plasma, Platelets, Whole Blood); 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).	Biological: Cryoprecipitate; 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).; Biological: Red Blood Cells; RBCs are utilized as part of the Massive Transfusion protocol for hemorrhage control.; Other Names: RBCs; Biological: Plasma; Plasma is utilized as part of the Massive Transfusion protocol for hemorrhage control.; Biological: Platelets; Platelets are utilized as part of the Massive Transfusion protocol for hemorrhage control.; Biological: Whole Blood; Whole Blood is utilized as part of the Massive Transfusion protocol for hemorrhage control.
Active Comparator: Massive Transfusion Protocol (RBCs, Plasma, Platelets, Whole Blood); Only standard of care massive transfusion protocol products will be given, including red blood cells, plasma, platelets, and whole blood.	Biological: Red Blood Cells; RBCs are utilized as part of the Massive Transfusion protocol for hemorrhage control.; Other Names: RBCs; Biological: Plasma; Plasma is utilized as part of the Massive Transfusion protocol for hemorrhage control.; Biological: Platelets; Platelets are utilized as part of the Massive Transfusion protocol for hemorrhage control.; Biological: Whole Blood; Whole Blood is utilized as part of the Massive Transfusion protocol for hemorrhage control.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Mortality From Any Cause	Mortality from any cause	28 days after emergency department (ED) admission

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All Cause Mortality at 6 Hours	Mortality from any cause	6 hours after ED admission
All Cause Mortality at 24 Hours	Mortality from any cause	24 hours after ED admission
All Cause Mortality at 6 Months	Mortality from any cause	6 months after ED admission
All Cause Mortality at 12 Months	Mortality from any cause	12 months after ED admission
Death From Bleeding at 6 Hours	Death related to exsanguination	6 hours after ED admission
Death From Bleeding at 24 Hours	Death related to exsanguination	24 hours after ED admission
Transfusion Requirements (Number of Units of Red Blood Cells (RBCs))	Number of units of RBCs	from time of pre-hospital care to 24 hours after ED admission
Transfusion Requirements (Number of Units of Plasma)	Number of units of plasma	from time of pre-hospital care to 24 hours after ED admission
Transfusion Requirements (Number of Units of Platelets)	Number of units of platelets	from time of pre-hospital care to 24 hours after ED admission
Transfusion Requirements (Number of Units of Cryoprecipitate)	Number of units of cryoprecipitate	from time of pre-hospital care to 24 hours after ED admission
Destination of Participant at Time of Discharge From Hospital	Disposition of subject at time of discharge	at the time of discharge from hospital, about 1-8 days after admission
Quality of Life as Assessed by EuroQol-5 Dimension-5 Level (EQ5D-5L)	EQ5D-5L is reported as an index score ranging from 0 to 1, where 0 is the health state equivalent to dead and 1 is the health state equivalent to full health.	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	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)	EQ5D-5L is reported as an index score ranging from 0 to 1, where 0 is the health state equivalent to dead and 1 is the health state equivalent to full health.	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	6 months after ED admission
Hospital Resource Use as Assessed by Number of Ventilator Days	Number of ventilator days during hospitalization	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	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	Day of hospital discharge or 28 days after ED admission (whichever comes first)

Collaborators and Investigators

• Sponsor: Bryan Cotton
• Collaborators: Queen Mary University of London; NHS Blood and Transplant
• Investigators: Principal Investigator: Bryan A Cotton, MD, The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): November 1, 2022

Study Registration Dates

• First Submitted: January 6, 2021
• First Submitted That Met QC Criteria: January 9, 2021
• First Posted (Actual): January 12, 2021

Study Record Updates

• Last Update Posted (Actual): May 12, 2023
• Last Update Submitted That Met QC Criteria: May 10, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage
• Other Study ID Numbers: HSC-MS-19-0272; ISRCTN14998314 (Registry Identifier: International Standard Randomised Controlled Trial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No