E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
head injury following a blow to the head |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Symptoms and general pathology [C23] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10019196 |
E.1.2 | Term | Head injury |
E.1.2 | System Organ Class | 10022117 - Injury, poisoning and procedural complications |
|
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 |
Combined proportion of unfavourable neurological outcomes at 6 months: severe disability (defined as GOSE scores 2-4) or death (GOSE score 1). |
|
E.2.2 | Secondary objectives of the trial |
Probability of an equal or greater GOSE level at 6 months compared to the probability of a lesser GOSE level, using a proportional odds model Proportion of surviving patients with unfavourable neurological outcome (GOSE 2-4) at 6 months Quality of life assessment (SF-12 and EQ-5D) at 6 months Mortality at 6 months Rate of proximal deep venous thrombosis detected during screening by compression Doppler ultrasound Proportion of patients with composite thrombotic vascular events (DVT, PE, myocardial infarction, cardiac arrest and cerebrovascular events) at 6 months Cost effectiveness analysis at 6 months (based on EQ-5D) |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Erythropoietin in Traumatic Brain Injury: Acute Kidney Indury (EPO-AKI) version 4 dated 18 March 2011 Objectives: to determine whether in patients with TBI, EPO therapy reduces the risk for, severity of, and duration of AKI, compared to placebo. Erythropoietin in Traumatic Brain Injury: Biomarker Part (EPOBiomarker) version 4 dated 18 March 2011 Objectives: to determine whether in patients with TBI: a) EPO therapy reduces the release of biomarkers NGAL, cystatin-C and L-FABP compared to their release in those receiving placebo b) The release of these biomarkers predicts the occurrence, severity, duration of and recovery from AKI Brain Injury Markers In Serum and CSF Sub-Study version 4 dated 18 March 2011 Objectives: In patients with moderate and severe TBI, administration of EPO will improve neurological outcome and reduce the release of markers of brain injury in cerebrospinal fluid (CSF) and blood serum. |
|
E.3 | Principal inclusion criteria |
Patients with non-penetrating moderate (GCS 9-12) or severe (GCS 3-8) TBI admitted to the ICU who: Are ≥ 15 to ≤ 65 years of age Are < 24 hours since primary traumatic injury Are expected to stay ≥ 48 hours Have a haemoglobin not exceeding the upper limit of the applicable normal (ULN) reference range in clinical use at the treating institution Have written informed consent from legal surrogate |
|
E.4 | Principal exclusion criteria |
GCS = 3 and fixed dilated pupils History of DVT, PE or other thromboembolic event Chronic hypercoagulable disorder, including known malignancy EPO in the last 30 day Pregnancy or lactation or 3 months post partum Uncontrolled hypertension Acute myocardial infarct within the past 12 months Past history of epilepsy with seizures in past 3 months Expected to die imminently Inability to perform lower limb ultrasounds lKnown sensitivity to mammalian cell derived products Hypersensitivity Pure red cell aplasia End stage renal failure Severe pre-existing physical or mental disability or severe co-morbidity Treatment with any investigational drug within 30 days before enrolment Not in the best interest of the patient |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of unfavourable neurological outcomes at 6 months: severe disability (defined as GOSE 2-4), or death (GOSE score 1). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Probability of an equal or greater GOSE level at 6 months compared to the probability of a lesser GOSE level, using a proportional odds model Proportion of surviving patients with unfavourable neurological outcome (GOSE 2-4) Quality of life assessment Mortality Rate of proximal deep venous thrombosis detected during screening by compression Doppler ultrasound Proportion of patients with composite thrombotic vascular events (DVT,PE, myocardial infarction, cardiac arrest and cerebrovascular events)Cost-effectiveness analysis |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.4 | Double blind | Yes |
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 | 2 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Finland |
France |
Germany |
New Zealand |
Saudi Arabia |
Singapore |
|
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
|
6 month follow up is completed for the last patient in the trial. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |