E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severely injured trauma patients with bleeding refractory to standard treatment. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053476 |
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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 |
To evaluate the efficacy and safety of rFVIIa NovoSeven/NiaStase versus placebo as adjunct therapy in trauma patients with active hemorrhage, refractory to standard treatment |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Informed consent obtained before any trial-related activities 2. Trauma injury blunt and/or penetrating with evidence of active torso hemorrhage refractory to standard treatment proximal to the inguinal creases, proximal/medial to the axillae at the time of randomization 3. Evidence of active torso hemorrhage at the time of randomization is defined as a. Presence of acidosis lactate 6 mmol/l 2 times the local upper limit of normal or Base Deficit 5 mEq/l documented within 30 minutes prior to randomization or b. Presence of hypotension systolic blood pressure SBP 8804; 90mmHg documented at any point in time within 30 minutes prior to randomization or c. Presence of ongoing volume loading at a minimal rate of 1L/h RBC or any other IV fluid/blood product up to the point of randomization and with continuing similar or greater need per the Investigator s judgment 4. Receipt of a minimum of 4 units of RBC at the time of randomization and the ability to administer study drug as soon as possible upon the completion of the 4th unit and before the completion of the 8th unit of RBC 5. Male or female patients, between 18 and 65 years of age OR of legal age to consent for participation in an investigational drug trial as per local law Informed Consent implies either i Informed Consent by the patient or ii Informed consent by the Patients Legally Authorized Representative or iii Authorization by independent physician in countries allowing waiver of Informed Consent according to the procedure described in Section 17 . Trial-related activities include any procedure that would not have been performed as part of standard care of the patient Section 17 . |
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E.4 | Principal exclusion criteria |
1. Known age of 18 years or 65 years or not of legal age to consent for participation in an investigational drug trial as per local law 2. Moribund as defined by a. pH 7.1 or b. Lactate 15 mmol/l or c. Base deficit BD 15 mEq/l or d. SBP 8804; 50 mmHg or use of repeated bolus vasopressor treatment to support the blood pressure prior to randomization bolus vasopressor use for reasons other than hypovolemia i.e. spinal cord injury, anesthetic induction does not exclude the patient or e. Anatomical injury incompatible with life e.g. multiple cardiac wounds, unrepairable liver or pelvic injury or f. Glasgow Coma Scale GCS score never higher than 5 at any time between injury and randomization in patients with any type of injury , or g. Cardiac arrest any time from injury until Randomization. 3. Evidence of head injury and suspicion of severe brain trauma as defined by a. GCS 8 and evidence on cranial CT scan of AIS 2 or b. Abnormal physical examination e.g. decorticate posturing indicative of brain injury or c. Traumatic intracranial injury of AIS 2 demonstrated by CT scan 4. Time from injury to randomization 12 hours. 5. Estimated time of injury to admission 4 hours 6. Primary bleeding source localized to the extremities as per the Investigator s judgment 7. Treatment with aprotinin and aPCC Activated Prothrombin Complex Concentrate or intention to treat with aprotinin and aPCC from time of injury through Day 5 8. Known history of thromboembolic events within 30 days 9. Presence of spinal cord injury above T6 with paralysis 10. Total body surface area burns 2 3 8805; 40 evaluated by the Investigator according to Lund-Browder chart for estimating the extent of burns, Appendix O 11. Known or suspected pregnancy 12. Previous randomization in this trial 13. Known participation in an investigational drug/device trial within the last 30 days 14. Estimated body weight 43 kg 15. Known or suspected allergy to trial product s or related products 16. Known presence of congenital bleeding disorder |
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E.5 End points |
E.5.1 | Primary end point(s) |
4.2 Primary Endpoints Efficacy Days alive and free of organ failure requiring life support through Day 30 Safety Adverse events from Randomization through Hour 48 Serious adverse events SAEs from Randomization through Day 90 |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Information not present in EudraCT |
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 | Yes |
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.8.3 |
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.8.5 | The trial involves multiple Member States | Yes |
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 |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 5 |