Condition category
Injury, Occupational Diseases, Poisoning
Date applied
11/07/2016
Date assigned
11/07/2016
Last edited
18/07/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Major trauma accounts for a significant number of deaths worldwide, and is one of the most frequent causes of death in people under the age of 40. A large number of these deaths are caused by major bleeding as a result of the trauma (traumatic haemorrhage). Patients with traumatic heamorrhage are currently given clear fluids but military and civilian research suggests that survival increases if hospital patients receive blood products (red blood cells and freeze-dried plasma) instead. The best treatment for bleeding patients before reaching hospital is uncertain. Giving too much fluid to improve blood pressure can increase bleeding. Therefore only small amounts of clear fluid are given. Some pre-hospital doctors now give red blood cells instead. Animal research suggests that this is better than clear fluids, and that adding plasma is better still. Some studies in humans support this however other research has found no benefit. There is currently no good quality evidence exists to show whether giving blood products before hospital, saves lives. The aim of this study is to find out whether giving blood products to badly injured adult patients, before reaching hospital improves their clinical condition and survival.

Who can participate?
Patients believed to be over the age of 16 who have sustained a serious injury leading to major blood loss.

What does the study involve?
Participants are randomly allocated to one of two groups at the scene of the emergency. Those in the first group receive fluids through a drip, with up to four bags of normal saline (salt water). Those in the second group receive two units of concentrated red blood cells and two units of freeze dried plasma (straw like fluid that makes up the liquid part of blood). Participants in both groups are followed up for 30 days to find out if any patients died (of their injuries or otherwise), as well as the speed they are able to clear lactic acid from their tissues (indicator of good blood flow). Blood pressure, heart rate, blood clotting and whether patients need organ support are also monitored while they are on intensive care.

What are the possible benefits and risks of participating?
There are no guaranteed direct benefits involved with participating in this study however the blood product treatment could be shown to be more effective than standard treatment. There are no notable risks involves for those participating in this study.

Where is the study run from?
Pre-hospital emergency medicine and major trauma centres in the West Midlands, Dorset & Somerset and in the East of England (UK)

When is the study starting and how long is it expected to run for?
October 2015 to April 2020

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
Miss Gemma Slinn
g.slinn@bham.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Miss Gemma Slinn

ORCID ID

Contact details

Birmingham Clinical Trials Unit
University of Birmingham
Birmingham
B15 2TT
United Kingdom
+44 121 415 9100
g.slinn@bham.ac.uk

Additional identifiers

EudraCT number

2015-001401-13

ClinicalTrials.gov number

Protocol/serial number

31157

Study information

Scientific title

A multi­centre randomised controlled trial of pre­hospital blood product administration versus standard care for traumatic haemorrhage

Acronym

RePHILL

Study hypothesis

The aim of this study is to investigate whether giving blood products (red blood cells and freeze-dried plasma) to badly injured adult patients, before reaching hospital improves their clinical condition and survival.

Ethics approval

South Central - Oxford C Research Ethics Committee, 15/12/2015, ref: 15/SC/0691

Study design

Randomised; Interventional; Design type: Treatment, Drug

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Injuries and emergencies, Primary sub-specialty: Injuries and emergencies; UKCRC code/ Disease: Injuries/ Certain early complications of trauma

Intervention

Participants are randomised in a 1:1 ratio to receive:

Crystalloid resuscitation: Consisting of up to 4 x 250 mL bags of 0.9% sodium chloride (normal saline). These will be administered as boluses of 250 mL to maintain a radial pulse

Pre-Hospital Blood Products (BHBP) resuscitation: Consisting of up to 2 units of PRBC and 2 units of LyoPlas. These will be administered as boluses consisting of a single unit of blood product, given in the sequence: PHBP, LyoPlas, PHBP, LyoPlas.
LyoPlas N-w is a freeze dried plasma product derived from a single donation and is licenced for use in the same indication as fresh frozen plasma. LyoPlas N-w is licensed for use in Germany as a medicinal product under the Marketing Authorisation Number PEI.H.03075.01.1.
PRBC are a concentrated preparation of red blood cells that is obtained from whole blood by removing the plasma (as by centrifugation). The PRBC used in RePHILL will be blood group O, RhD negative, Kell negative from NHS Blood and Transplant national stocks supplied by the blood banks that are supporting this trial.

Patients receive the trial interventions on-scene, because of the emergency nature of this trial, patients are considered randomised when the transport box containing the interventions is opened. Follow-up will comprise of standard care follow-up for patients that have a traumatic injury, no further trial-specific procedures will be undertaken after the delivery of the interventions but we will collect data pertaining to the RePHILL outcome measures for up to 30 days post-injury.

Intervention type

Other

Phase

Phase III

Drug names

Primary outcome measures

1. 1. Episode mortality is measured by whether or not the patient is still alive up to 30 days post injury up to 30 days post injury
2. Lactate clearance is measured by obtaining a lactate measurement at randomisation and a repeat measurement two hours post-randomisation

Secondary outcome measures

1. All-cause mortality rate is measured by whether or not the patient is still alive within 3 hours of randomisation
2. Pre-hospital time and type and volume of fluid is measured by the pre-hospital emergency medical team at on-scene.
3. Vital signs (systolic blood pressure, heart rate, capillary oxygen saturation) are measured at scene, on arrival at ED and at 2, 6, 12 and 24 hours after arrival at ED
4. Venous lactate concentration is measured by the receiving hospital medical team on arrival at ED and at 2 hours after arrival at ED
5. Trauma-induced coagulopathy (defined as International Normalised Ratio (INR) >1.5) is measured by measuring clotting factors on arrival at ED and at 2 and 6 hours after arrival at ED
6. Coagulation is measured using viscoelastically by rotational thromboelastometry on arrival at ED
7. Platelet function is measured using multiple electrode impedence aggregometery on arrival at ED
8. 8. Total blood product receipt is measured by recording fluids given to the patient at 6, 12 and 24 hours after arrival at ED
9. Acute respiratory distress syndrome (ARDS) is measured by the presence of clinical symptoms within the first 7 days after injury
10. Transfusion-related complications are measured by the presence of clinical symptoms up to 30 days post injury
11. Organ failure-free days are measured using the Sepsis-related Organ Failure Assessment (SOFA) score up to 30 days post injury

Overall trial start date

01/10/2015

Overall trial end date

30/04/2020

Reason abandoned

Eligibility

Participant inclusion criteria

1. Traumatic injury
2. Pre-Hospital Emergency Medical team attend
3. Hypotension (SBP <90mmHg or absence of palpable radial pulse) believed to be due to traumatic haemorrhage

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 490; UK Sample Size: 490

Participant exclusion criteria

1. Children (known or apparently aged <16 years)
2. Refusal of blood product administration; known Jehovah’s Witness
3. Pregnancy (known or apparent)
4. Isolated head injury

Recruitment start date

01/10/2016

Recruitment end date

31/01/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University Hospitals Birmingham NHS Foundation Trust
Queen Elizabeth Hospital Mindelsohn Way
Birmingham
B15 2WB
United Kingdom

Trial participating centre

West Midlands Ambulance Service NHS Foundation Trust
Trust Headquarters Millennium Point Waterfront Business Park Waterfront Way
Brierley Hill
DY5 1LX
United Kingdom

Trial participating centre

West Midlands Air Ambulance/ MERIT
Midlands Air Ambulance Charity Hawthorn House Dudley Road
Stourbridge
DY9 8BQ
United Kingdom

Trial participating centre

Warwickshire and Northamptonshire Air Ambulance
The Air Ambulance Service Hazell House Burnthurst Lane
Princethorpe
CV23 9QA
United Kingdom

Trial participating centre

Yorkshire Ambulance Service
Headquarters, Springhill Brindley Way Wakefield 41 Business Park
Wakefield
WF2 0XQ
United Kingdom

Trial participating centre

Yorkshire Air Ambulance
Cayley House 10 South Lane
Elland
HX5 0HQ
United Kingdom

Trial participating centre

East of England Ambulance Service NHS Trust
East of England Ambulance Service NHS Trust Headquarters Whiting Way Melbourn
Melbourn
SG8 6EN
United Kingdom

Trial participating centre

MAGPAS
Centenary House St. Mary's Street
Huntingdon
PE29 3PE
United Kingdom

Trial participating centre

East Anglian Air Ambulance
Hangar E Gambling Close Norwich Airport
Norwich
NR6 6EG
United Kingdom

Trial participating centre

Essex & Herts Air Ambulance
Essex and Herts Air Ambulance Trust Flight House Earls Colne Business Centre Earls Colne Business Park Earls Colne
Colchester
CO6 2NS
United Kingdom

Trial participating centre

East Midlands Ambulance Service NHS Trust
Trust Headquarters 1 Horizon Place Mellors Way Nottingham Business Park
Nottingham
NG8 6PY
United Kingdom

Trial participating centre

Derbyshire, Leicestershire and Rutland Air Ambulance
35 King Street
Belper
DE56 1PX
United Kingdom

Trial participating centre

Warwickshire and Northamptonshire Air Ambulance
The Air Ambulance Service Hazell House Burnthurst Lane
Princethorpe
CV23 9QA
United Kingdom

Trial participating centre

University Hospitals Coventry and Warwickshire NHS Trust
University Hospital Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom

Trial participating centre

University Hospitals of North Midlands NHS Trust
Royal Stoke University Hospital Newcastle Road
Stoke-on-Trent
ST4 6QG
United Kingdom

Trial participating centre

North Bristol NHS Foundation Trust
Southmead Hospital Southmead Road Westbury-on-Trym
Bristol
BS10 5NB
United Kingdom

Trial participating centre

The Leeds Teaching Hospital NHS Trust
Leeds General Infirmary Great George Street
Leeds
LS1 3EX
United Kingdom

Trial participating centre

South Tees Hospital NHS Foundation Trust
James Cook Hospital Marton Road
Middlesbrough
TS4 3BW
United Kingdom

Trial participating centre

Hull and East Yorkshire Hospitals NHS Trust
Hull Royal Infirmary Anlaby Road
Hull
HU3 2JZ
United Kingdom

Trial participating centre

Sheffield Teaching Hospitals NHS Foundation Trust
Northern General Hospital Herries Road
Sheffield
S5 7AU
United Kingdom

Trial participating centre

Cambridge University Hospitals NHS Foundation Trust
Addenbrooke’s Hospital Cambridge Biomedical Campus Hills Road
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Norfolk & Norwich University Hospitals NHS Foundation Trust
Norfolk and Norwich University Hospital Colney Lane
Norwich
NR4 7UY
United Kingdom

Trial participating centre

Nottingham University Hospitals NHS Trust
Queen’s Medical Centre Derby Road
Nottingham
NG7 2UH
United Kingdom

Sponsor information

Organisation

University Hospitals Birmingham NHS Foundation Trust

Sponsor details

Trust HQ
PO BOX 9551
Queen Elizabeth Medical Centre
Edgbaston
Birmingham
B15 2TH
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal. A protocol paper will be published within the next six months.

Intention to publish date

30/04/2021

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

18/07/2016: Verified study status with principal investigator.