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

Completed

Phase 2 Results N/A

Trial Description

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:
1. The efficacy of Eptacog alfa in preventing or reducing rebleeding after surgery for spontaneous supratentorial ICH; and
2. The safety of product administration

Detailed Description

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.

Conditions

Interventions

  • Saline Drug
    Other Names: Sodium Chloride
    Intervention Desc: Used as placebo for injection.
  • Eptacog alfa (NovoSeven)Drug
    Intervention Desc: It is a vitamin K-dependent glycoprotein that is structurally similar to human plasma-derived factor VIIa. It is a recombinant product, manufactured using DNA biotechnology.
  • RfVIIa Biological
    Other Names: Niastase RT
    Intervention Desc: Patients with spontaneous supratentorial ICH will be treated with rFVII after hematoma evacuation
    ARM 1: Kind: Experimental
    Label: 1
    Description: Patients treated with recombinant FVIIa
  • RFactor VIIa (Eptacog alfa, NovoNordisk) Drug
    Intervention Desc: rFVIIa will be admistered as single bolus at the dosage of 100 mcg/Kg b.w.
    ARM 1: Kind: Experimental
    Label: 1
    Description: Patients treated with recombinant FVIIa
  • Sodiun chloride 0.9% Other
    Intervention Desc: Bolus injection of sodium chloride 0.9% after surgical hematoma removal
    ARM 1: Kind: Experimental
    Label: 2
    Description: Patients with spontaneous supratentorial ICH included in this arm will be treated with placebo

Trial Design

  • Allocation: Randomized
  • Masking: Single Blind (Investigator)
  • Purpose: Treatment
  • Endpoint: Efficacy Study
  • Intervention: Parallel Assignment

Patient Involvement

Patients will be randomized to either Eptacog alfa or saline. 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). 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.

Outcomes

Type Measure Time Frame Safety Issue
Primary Evaluate the efficacy of Factor VIIa (Eptacog alfa) in preventing or reducing rebleeding after surgery for spontaneous supratentorial ICH.
Secondary Safety of product administration.
Primary Evaluate the efficacy of Factor VIIa (Eptacog alfa) in preventing or reducing rebleeding after surgery for spontaneous supratentorial ICH 4 years Yes
Secondary Safety of product administration 4 years Yes

Sponsors