Inflammatory response in major injury and recovery - erythropoietin

ISRCTN	ISRCTN40935649
DOI	https://doi.org/10.1186/ISRCTN40935649
Protocol serial number	4
Sponsor	Abertawe Bro Morgannwg University Health Board
Funder	Abertawe Bro Morgannwg University Health Board

Submission date: 17/09/2015
Registration date: 17/03/2016
Last edited: 07/01/2019

Recruitment status: Stopped
Overall study status: Stopped
Condition category: Injury, Occupational Diseases, Poisoning

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

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

Contact information

Prof Ian Pallister
Scientific

Heol Maes Eglwys
Morriston
Swansea
SA6 6NL
United Kingdom

Study information

Primary study design	Interventional
Study design	Multi-centre single-blind randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Inflammatory response in major injury and recombinant human erythropoietin
Study acronym	IRMINE
Study objectives	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(s)	Wales REC 3, 26/01/2016, ref: 15/WA/0361
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	rhEPO
Primary outcome measure(s)	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.
Key secondary outcome measure(s)	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
Completion date	30/12/2017
Reason abandoned (if study stopped)	Lack of funding/sponsorship

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	60 Years
Sex	All
Target sample size at registration	400
Key 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
Key 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
Date of first enrolment	04/10/2016
Date of final enrolment	04/01/2017

Locations

Countries of recruitment

United Kingdom
Wales

Study participating centre

Morriston Hospital

Heol Maes Eglwys
Morriston
Swansea
SA6 6NL
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

07/01/2019: Recruitment into the trial was suspended in December 2018 pending the result of the application for funding for the full MCRCT from EME. This was unsuccessful and so the trial was formally stopped completely on 12/07/2018.
10/10/2016: Ethics approval information added.