Condition category
Injury, Occupational Diseases, Poisoning
Date applied
17/09/2015
Date assigned
17/03/2016
Last edited
10/10/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Blunt trauma, also known as blunt force trauma, is a severe physical injury caused by impact of the head or body with a blunt object or surface. One of the most common injuries associated with blunt trauma is damage to the kidneys. The kidneys play a vital role in the body, producing a number of different hormones. One of these hormones, erythropoietin (EPO) stimulates the bone marrow to produce more red blood cells. Previous studies have shown that giving patients a manufactured version of this hormone, known as recombinant human erythropoietin (rhEPO) can help to protect patients with severe injuries from death. The reason why this happens is not known, however further studies have suggested that rhEPO may actually influence the immune system, reducing the risk of infection. The aim of this study is to find out whether treatment with rhEPO can help reduce organ failure rates and improve recovery in adults admitted to intensive care with injuries caused by blunt trauma.

Who can participate?
Adults admitted to intensive care unit (ITU) with blunt trauma with an injury severity score of at least 16.

What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first groups are given an injection under the skin (subcutaneous injection) of rhEPO 1, 8 and 15 days after they are admitted to the ITU. Participants in the second group are given a subcutaneous injection of a dummy (placebo) 1, 8 and 15 days after they are admitted to the ITU. Participants in both groups are monitored for 30 days after they are discharged from ITU in order to establish how many have multiple organ failure, how many survive and the time spent on the ITU ward.

What are the possible benefits and risks of participating?
Participants who receive rhEPO may benefit from a faster recovery as a result of the treatment. Risks of taking part are small however some patients may experience side-effects of rhEPO such as high blood pressure.

Where is the study run from?
Morriston Hospital (UK)

When is the study starting and how long is it expected to run for?
September 2015 to December 2017

Who is funding the study?
Abertawe Bro Morgannwg University Health Board (UK)

Who is the main contact?
Professor Ian Pallister

Trial website

Contact information

Type

Scientific

Primary contact

Prof Ian Pallister

ORCID ID

Contact details

Heol Maes Eglwys
Morriston
Swansea
SA6 6NL
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

4

Study information

Scientific title

Inflammatory response in major injury and recombinant human erythropoietin

Acronym

IRMINE

Study hypothesis

The use of recombinant human erythropoietin (rhEPO) reduces organ failure after severe trauma in adults, by effects on the clinical, cellular & biomolecular manifestations of the systemic inflammatory response to injury and the haemopoeitic bone marrow.

Ethics approval

Wales REC 3, 26/01/2016, ref: 15/WA/0361

Study design

Multi-centre single-blind randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

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

Condition

Major Trauma (Injury Severity Score 16+)

Intervention

Participants are randomly allocated to one of two groups.

Intervention group: Participants receive rhEPO (40,000 units) via subcutaneous injection on day 1, 8 and 15 post admission, while the patient remains in ITU.
Control group: Participants receive a subcutaneous injection of a placebo on day 1, 8 and 15 post admission, while the patient remains in ITU.

Participants are followed up for 30 days after discharge from ITU to calculate mortality rates at 30 days.

Intervention type

Drug

Phase

Phase IV

Drug names

rhEPO

Primary outcome measures

Multiple organ failaure is monitored using the Denver multiple organ failure score at baseline, day 3 and then daily until discharge from ITU, mortality or 30 days.

Secondary outcome measures

1. Treatment plan (surgery and/or interventional radiology) is recorded at baseline
2. Length of ITU stay is determined at 30 days, time of discharge from ITU or death
3. Critical care support required is measured by mode and duration of mechanical ventilation and inotrope infusion daily throughout ITU stay
4. Length of hospital stay is determined from patient notes at 30 days, discharge or death
5. Thromboembolic vascular events (TVE) rate is determined from reviewing patient notes at 30 days, discharge or death
6. The inflammatory response to injury is measured using the Systemic Inflammatory Response clinical score (SIRS) calculated daily and using cytokine and cellular protein assays at on blood samples taken daily, while on ITU
7. Presence of Persistent Inflammation/Catabolism syndrome (PICS) is calculated from clinical observations and protein assays from day 10, only in those remaining on ITU at that point
8. Leukocyte progenitor proliferation/differentiation in bone marrow aspirates is assessed using flow cytometry and colony forming unit assays obtained on day 2 while on ITU, and subsequently in those requiring pelvic fracture surgery
9. Mitochondrial respiratory function is measured using bioenergetic profile assays on blood obtained daily until while on ITU

Overall trial start date

01/01/2016

Overall trial end date

30/12/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged between 18-60 years
2. Blunt trauma patients admitted to ITU
3. Injury severity score (ISS) at least 16
4. ITU stay expected to last at least 3 days

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

400

Participant exclusion criteria

1. Pregnancy (an admission pregnancy test is routine in all female trauma patients who are of child-bearing age)
2. Presence of a severe isolated traumatic brain injury
3. Presence of any blood-borne infections e.g. HIV, hepatitis B or C.
4. Presence of any known malignancies
5. Presence of not been consented by a personal legal representative or a professional legal representative if the former is not available
6. Are already participating in another clinical trial
7. Presence of a contra-indication to thromboprophylaxis
8. Presence of contra-indications for rhEPO:
8.1. Uncontrolled hypertension
8.2. Known sensitivity to mammalian cell derived products
8.3. Hypersensitivity to the active substance or to any of the excipients
8.4. Severe coronary, peripheral arterial, carotid or cerebral vascular disease, including patients with recent myocardial infarction or cerebral vascular accident
8.5. Patients who have developed Pure Red Cell Aplasia (PRCA) following treatment with any erythropoietin
8.6. A history of thrombo-embolic vascular (TVE) events

Recruitment start date

04/10/2016

Recruitment end date

04/01/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Morriston Hospital
Heol Maes Eglwys Morriston
Swansea
SA6 6NL
United Kingdom

Sponsor information

Organisation

Abertawe Bro Morgannwg University Health Board

Sponsor details

1st Floor
Institute of Life Science 2
Swansea University
Singleton Park
Swansea
SA2 8PP
Swansea
SA28PP
United Kingdom
+44 1792-750456
abm.rd@wales.nhs.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Hospital/treatment centre

Funder name

Abertawe Bro Morgannwg University Health Board

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The data generated from this study will provide a very high level of evidence relating to the efficacy or otherwise of rhEPO in the major trauma situation. The findings of the study will be presented at scientific meetings and submitted for publication in peer reviewed journals. In addition, a lay-person summary of findings in a post-trial news letter will be made available to all participants and relatives in both a web based format and sent to them if preferred.

Intention to publish date

30/06/2018

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

10/10/2016: Ethics approval information added.