Efficacy and safety of two dose regimens of Octaplex® in patients with intracranial haemorrhage related to oral anticoagulant therapy

INR at 10 ± 5 minutes after the end of injection in patients with intracranial haemorrhage related to oral anticoagulant therapy, measured by local laboratories (standard method).

Efficacy:
1. Laboratory parameters (coagulation): INR, prothrombin time (PT), thrombin generation assay (TGA), coagulation factors II, VII, IX and X, protein C and protein S at 10 ± 5 minutes, 1, 3, 6 and 24 hours after the end of injection. All these parameters will be analysed by local or central laboratory using standard methods.
2. Medical imaging (CT scan): volume of haematoma at 48 hours after the end of injection (or earlier in case of neurological worsening assessed by National Institutes of Health [NIH] Stroke Scale); the computed tomography images at T0 and T48 hours will be analysed by the central neuroradiology centre with the software OSIRIX
3. Clinical status: Glasgow Coma Scale (score: 3 - 15) and NIH Stroke Scale at 1, 24 and 48 hours, and on days 3 and 30 (or earlier if patient discharged) after the end of injection
4. Global outcome:
4.1. Survival (is the patient dead? Yes or No)
4.2. Extended Glasgow Outcome Scale (GOS) (score: 1 - 8, 1 = dead, 8 = upper good recovery)
4.3. Modified Rankin Scale (MRS) (score: 0 - 6, 0 = no symtoms at all, 6 = dead)
4.4. Barthel Index (score: 0 - 100, 100 = patient is continent, feeds himself, dresses himself, gets up out of bed and chairs, bathes himself, walks at least a block, and can ascend and descend stairs)
All measured on day 30 (or earlier if patient discharged) after the end of injection.
5. Overall clinical response: this assessment will be done by the investigator using a verbal rating scale:
5.1. None: in spite of sufficient treatment uncontrolled intracranial bleeding growth requiring additional measures
5.2. Moderate: in spite of sufficient treatment uncontrolled intracranial bleeding and haematoma growth; no additional measures required
5.3. Excellent: intracranial bleeding and haematoma growth under control, comparable to a normal patient
Measured 48 hours after the end of injection.

Safety:
6. Study drug actually received
7. Adverse events (AEs) during the whole stay in all patients. AEs will be followed closely by a Data Monitoring Committee (DMC) whose assignment will be to identify possible thromboembolic complications. The DMC will be entitled to issue recommendations to the sponsor and the investigators regarding the continuation or the modification of the study if there is a suspicion of increased risk of thromboembolic complications in the high dose group.
8. Vital signs: continuous monitoring of arterial blood pressure, heart rate, respiratory rate and body temperature during the whole stay in the investigator's ward; recording of values and abnormalities at 10 ± 5 minutes, 1, 6, 24 and 48 hours and on days 3 and 30 (or earlier if patient discharged) after the end of injection
9. Electrocardiogram (ECG): continuous surveillance during the whole stay in the investigator's ward; recording of abnormalities at 10 ± 5 minutes, 1, 3, 6, 24 and 48 hours and on days 3 and 30 (or earlier if patient discharged) after the end of injection
10. Laboratory parameters (coagulation markers): D-dimers, prothrombin fragments F1+2 at 10 ± 5 minutes, 1, 3, 6 and 24 hours after the end of injection
11. Other laboratory parameters: troponins, electrolytes, urea, creatinine, liver function and haematology at 24 hours after the end of injection
12. Digital glucose at 24 hours after the end of injection

Quality of life measurements:
13. Pharmaco-economic patient questionnaire at month 3
14. 36-item short form health survey (SF-36) questionnaire at month 3