Efficacy and Safety of Factor VIIa on Rebleeding After Surgery for Spontaneous Intracerebral Hemorrhage (ICH)

Study Overview
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Brief Summary
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Although the role of surgical treatment is still controversial, surgical evacuation of intracerebral hematoma is a frequent practice. Rebleeding is a frequent complication in patients submitted to hematoma evacuation. It has been reported that smaller postoperative volume of hematoma is associated with a better outcome. The investigators hypothesize that the administration of Factor VIIa (Eptacog alfa) immediately after surgical evacuation of the hematoma can reduce postoperative rebleeding. Aims of the Study: This study will investigate: The efficacy of Eptacog alfa in preventing or reducing rebleeding after surgery for spontaneous supratentorial ICH; and The safety of product administration

Detailed Description
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The primary endpoint is the evaluation of efficacy of Factor VIIa (Eptacog alfa, NovoSeven, Novo Nordisk) on rebleeding after surgery for primary supratentorial ICH. All patients included in the study will perform a CT scan within 3 hours before surgery, then immediately after surgery, and 18-30 hours after surgery. The hematoma volume will be evaluated by a multi-slice CT scan. All CT scan images will be sent to the Coordinating Center where the hematoma volume will be evaluated by a dedicated software by the same investigator who will be unaware of the treatment (investigator- blinded study). SAFETY EVALUATION: Seventeen episodes of thrombotic spontaneous adverse events have been reported after administration of 480,000 standard doses of Eptacog alfa in hemophilic patients. These episodes include myocardial infarction, acute cerebrovascular thrombosis, disseminated intravascular coagulation (DIC), deep venous thrombosis (DVT) and pulmonary embolism. Before and after hematoma removal will be evaluated ECG, myocardiac enzymes, coagulation profile, CT scan (looking for ischemic events) and venous echodoppler ultrasound of lower extremities.

Official Title
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Efficacy and Safety of Factor VIIa (Eptacog Alfa) on Rebleeding After Surgery for Spontaneous Supratentorial Intracerebral Hemorrhage. A Randomized, Controlled, Open-Label, Investigator-Blinded Pilot Study

Conditions
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Intracerebral Hemorrhage

Intervention / Treatment
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* Drug: rFactor VIIa (Eptacog alfa, NovoNordisk)
* Drug: rFVIIa
* Other: Sodiun chloride 0.9%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, aged 18-75 years inclusive Intraparenchymal primary supratentorial intracerebral hemorrhage requiring surgical evacuation Any Glasgow Coma Score (GCS) score Surgery expected to be performed within 24 hours from symptoms onset Exclusion Criteria: Age below 18 Intraparenchymal hematoma secondary to rupture of cerebral aneurysm or bleeding of arteriovenous (A-V) malformation or cerebral tumors Contemporary involvement in another study Pregnancy Myocardial infarction in the six months preceding enrolment Coronary or carotid stents positioned in the six months preceding enrolment Solid organ transplant patients (e.g., heart, lung, liver, kidney) Pregnancy Myocardial infarction in the six months preceding enrolment Coronary and carotid stents positioned in the six months preceding enrolment Solid organ transplant patients (e.g., heart, lung, liver, kidney)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Patients treated with recombinant FVIIa | Drug: rFactor VIIa (Eptacog alfa, NovoNordisk)<br>* rFVIIa will be admistered as single bolus at the dosage of 100 mcg/Kg b.w.<br>Drug: rFVIIa<br>* Patients with spontaneous supratentorial ICH will be treated with rFVII after hematoma evacuation<br>|
| Placebo Comparator: 2<br>Patients with spontaneous supratentorial ICH included in this arm will be treated with placebo | Other: Sodiun chloride 0.9%<br>* Bolus injection of sodium chloride 0.9% after surgical hematoma removal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the efficacy of Factor VIIa (Eptacog alfa) in preventing or reducing rebleeding after surgery for spontaneous supratentorial ICH |  | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of product administration |  | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spontaneous intracerebral hemorrhage, ICH, intracerebral rebleeding, cerebral hematoma evacuation, cerebral hematoma volume