A multi-center, randomized, double-blind, parallel group, placebo controlled trial to evaluate the efficacy and safety of activated recombinant factor VII (rFVIIa/NovoSeven®/NiaStase®) in severely injured trauma patients with bleeding refractory to standard treatment
- Conditions
- Traumatic HemorrhageMedDRA version: 8.0Level: LLTClassification code 10053476
- Registration Number
- EUCTR2005-002059-41-AT
- Lead Sponsor
- ovo Nordisk A/S
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 5000
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) no
F.1.3.1 Number of subjects for this age range
1.Moribund as defined by any one of the following (only the most recent values prior to randomization are to be considered):
a.pH < 7.1* or
b.Lactate > 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)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method