Traumatic Hemorrhage MedDRA version: 8.0 Level: LLT Classification code 10053476
Conditions
Interventions
Trade Name: NovoSeven®
Product Name: NovoSeven
Product Code: rFVIIa
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: eptacog alfa (activated)
CAS Number: 102786-
Sponsors
Novo Nordisk A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Informed consent (Section 17) obtained before any trial-related activities (Trial-related activities are any procedure that would not have been performed as part of the patient’s standard care). 2.Trauma injury (blunt and/or penetrating) with evidence of active torso (proximal to the inguinal creases, proximal/medial to the axillae) and/or proximal lower extremity (above knee) hemorrhage refractory to blood component therapy and surgical hemostatic procedures at the time of randomization 3.“Evidence of active hemorrhage (torso and/or proximal lower extremity) at the time of randomization” is defined as: a.Presence of hypotension due to hypovolemia (systolic blood pressure (SBP) =90 mmHg) documented at any point in time within 30 minutes prior to randomization or b.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) or c.Presence of acidosis (lactate > 6 mmol/L (or 2 times the local upper limit of normal) or Base Deficit = 5 mEq/L) documented at any point in time within 30 minutes prior to randomization 4.Receipt of a minimum of 4 units of RBC at the time of randomization and the ability to administer first dose of study drug as soon as possible upon the completion of the 4th unit and no later than the completion of the 8th unit of RBC 5.Male or female patients, between 18-70 years of age OR of legal age to consent for participation in an investigational drug trial as per local law Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Moribund as defined by any one of the following (only the most recent values prior to randomization are to be considered): a.pH 15 mmol/l or c.Base deficit (BD) > 15 mEq/l or d.SBP = 50 mmHg or use of 2 boluses or more of vasopressor or continuous 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.Cardiac arrest (cessation of spontaneous circulation) any time from injury prior to randomization. 2.Evidence of head injury and suspicion of severe brain trauma as defined by any one of the following: a.Highest GCS score =5 , or b.Need for immediate open intracranial operation or c.Abnormal physical examination indicative of brain injury (e.g. decorticate posturing, localizing signs such as unequal pupils due to Traumatic Brain Injury) or d.Traumatic intracranial injury of AIS > 4 demonstrated by CT scan 3.Time from injury to dosing > 12 hours 4.Estimated time of injury to trial hospital admission > 4 hours 5.Primary bleeding source localized to the upper extremities or distal lower extremities as per the Investigator's judgment 6.Treatment with aprotinin, aPCC (Activated Prothrombin Complex Concentrate) or PCC (Prothrombin Complex Concentrate) 7.Known history of thromboembolic events within 30 days 8.Presence of spinal cord injury above T6 with paralysis 9.Total body surface area burns: 2° + 3° = 40% (evaluated by the Investigator according to Lund-Browder chart for estimating the extent of burns, Appendix O) 10.Known or suspected pregnancy 11.Previous randomization in this trial 12.Known participation in an investigational drug/device trial within the last 30 days 13.Estimated body weight < 43 kg 14.Known or suspected allergy to trial products or related products 15.Known presence of congenital bleeding disorder 16.Patient known or suspected of not being able to comply with this study protocol or indication of reluctance to participate in the trial (e.g. revealed by examination of an incapacitated patient's personal effects) *In case a low pH value (less than 7.1) is predominantly or partly due to a respiratory component, it is acceptable to assess moribund criterion 1.a. based on a "corrected pH value" calculated from one of the equations: In units of mmHg: Corrected pH = actual pH + (0.008 multiplied by each mmHg pCO2 above 40 mmHg). In units of kPa:Corrected pH = actual pH + (0.06 multiplied by each kPa pCO2 above 5.33)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Primary endpoints: Efficacy: • A primary endpoint of all cause 30 day mortality designed to show superiority of rFVIIa compared to placebo in blunt trauma patients If mortality is not superior, then • A primary endpoint designed to demonstrate non-inferiority of rFVIIa compared to placebo on all cause 30 day mortality and superiority of rFVIIa compared to placebo on pulmonary and/or renal dysfunction requiring ongoing medical intervention at Day 30 in blunt trauma patients Safety: • Adverse events from Randomization through Hour 48 in blunt and penetrating trauma patients • Serious Adverse Events (SAEs) from Randomization through Day 90 in blunt and penetrating trauma patients Prioritized Secondary Endpoint: Efficacy in Blunt Trauma Patients: • Days alive and free of pulmonary and/or renal dysfunction requiring ongoing medical intervention through Day 30 Other secondary endpoints: 15 minutes after administration of each dose: • Assessment of tissue bleeding response At 24 hours after the first dose of study drug: • Number of transfused units of red blood cells (RBC) • Number of transfused units of fresh frozen plasma (FFP) • Number of transfused units of platelets • Number of transfused units of cryoprecipitate/fibrinogen concentrate • Total number transfused allogeneic units At 48 hours after the first dose of study drug: • Number of transfused units of red blood cells (RBC) • Number of transfused units of fresh frozen plasma (FFP) • Number of transfused units of platelets • Number of transfused units of cryoprecipitate/fibrinogen concentrate • Total number of transfused allogeneic units • All cause Mortality Through Day 30 after the first dose of study drug: • Multi organ failure according to Appendix G • Single organ failure for pulmonary, renal, cardiovascular, and the hepatic systems • Ventilator-free days • ICU-free days • Hospital-free days At Day 30 after the first dose of study drug: • Composite endpoint of all-cause morta | — |
Countries
Czech Republic, Finland, Germany, Greece, Hungary, Italy, Portugal, Slovenia, Spain, Sweden, United Kingdom
Outcome results
None listed