E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Post-trauma multiple organ failure: a manifestation of the systemic inflammatory/immune response to major injuries. |
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E.1.1.1 | Medical condition in easily understood language |
This study will see if artificially made human erythropoietin helps people recover from serious injury quicker by boosting immunity through bone marrow or improving the way the body creates energy. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021459 |
E.1.2 | Term | Immunodeficiency secondary to trauma |
E.1.2 | System Organ Class | 100000004870 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028237 |
E.1.2 | Term | Multiple organ failure |
E.1.2 | System Organ Class | 100000004867 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10044461 |
E.1.2 | Term | Trauma |
E.1.2 | System Organ Class | 10022117 - Injury, poisoning and procedural complications |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10044541 |
E.1.2 | Term | Traumatic shock |
E.1.2 | System Organ Class | 10022117 - Injury, poisoning and procedural complications |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Objective: The IRMINE pilot will test the trial design and logistics in preparation for a bid for a multi-centre randomised controlled trial.
The pilot will evaluate the impact of recombinant human erythropoietin (rhEPO) on recovery in adult severe blunt trauma patients who need critical care/ITU support. This will be measured in terms of reducing organ failure as a marker of mortality, reflecting the body's abnormal inflammatory/immune response to injury, which can cause damage to the patient's own tissues and organs.
Principle Research Question: Does the use of recombinant human erythropoietin (rhEPO) reduce organ failure after severe trauma in adults?
A reduction in the body's abnormal immune response may help explain the beneficial protection of rhEPO if a decrease in organ failure is seen.
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E.2.2 | Secondary objectives of the trial |
a) To determine whether the use of recombinant human erythropoietin (rhEPO) reduces organ failure after severe trauma in adults. b) To understand the effect of rhEPO on the clinical, cellular & biomolecular manifestations of the systemic inflammatory response to injury. c) To identify whether human haemopoeitic bone marrow responds to rhEPO after severe injury. d) To determine whether rhEPO is associated with an increase in thromboembolic events despite appropriate standard of care prophylaxis. e) To determine whether the use of recombinant rhEPO reduces 30 day mortality after severe trauma in adults.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The patient is eligible to participate in the study if they: • have undergone a significant blunt trauma (injury severity score ≥16) • have been admitted to ITU with an expected stay >3 days. • are aged between 18-64 years on admission.
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E.4 | Principal exclusion criteria |
The patient will not be eligible to participate in the study if they: • Are pregnant (an admission pregnancy test is routine in all female trauma patients who are of child-bearing age). • Have a severe isolated traumatic brain injury. • Have any blood-borne infections e.g. HIV, hepatitis B or C. • Have any known malignancies. • Are already participating in another clinical trial. • Have a contra-indication to thromboprophylaxis. • Have contra-indications for rhEPO:- o Uncontrolled hypertension. o Known sensitivity to mammalian cell derived products. o Hypersensitivity to the active substance or to any of the excipients. o Patients who have severe coronary, peripheral arterial, carotid or cerebral vascular disease, including patients with recent myocardial infarction or cerebral vascular accident (within 3 months). o Patients who have developed Pure Red Cell Aplasia (PRCA) following treatment with any erythropoietin. o A history of thrombo-embolic vascular events (TVEs).
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E.5 End points |
E.5.1 | Primary end point(s) |
The IRMINE pilot will test trial recruitment and data collection processes and laboratory analysis for the purpose of confirming the practicalities of the methods described and assuring that they can be completed.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
We will collect clinical, process and laboratory data which will be useful in determining the potential effect size and ascertaining the quality of the data items collected rather than in analysis in this small sample.
The DMOF score will be calculated daily throughout the patients' ITU stay. The average length of stay on ITU for this group of trauma patients is 8 days.
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E.5.2 | Secondary end point(s) |
1. To understand the effect of rhEPO on the clinical, cellular & biomolecular manifestations of the systemic inflammatory response to injury.
2. To identify whether human haemopoeitic bone marrow responds to rhEPO after severe injury.
3. To determine whether rhEPO is associated with an increase in thromboembolic events despite appropriate standard of care prophylaxis.
4. To determine whether the use of rhEPO reduce 30 day mortality after severe trauma in adults. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Markers and mediators will be measured daily throughout the patients' ITU stay. The average length of stay on ITU for this group of trauma patients is 8 days.
2. Aspiration of haemopoeitic bone marrow will be performed on all subjects on Day2, and opportunistically again in those undergoing pelvic fracture surgery.
3. Frequency of Thromboembolic events (TEV) will be recorded while on ITU.
4. 30 day mortality will be recorded. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Mechanistic effect of the IMP on the immune system |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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For the pilot this will conclude after enrolement of the 10th subject and their monitoring upto 30 days post-admission or death if sooner. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 31 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 31 |