Clinical trial NCT00222625: rFVIIa in ICH in Patients Treated With Anticoagulants or Anti-Platelets
Official title: Randomized, Open, Prospective, Multicenter Pilot Study to Evaluate the Efficacy and Safety of Activated Recombinant Factor VII in Acute Intracerebral Haemorrhage in Patients Treated With Oral Anticoagulants or Antiplatelets Agents.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Intracerebral Hemorrhage
Keywords: Intracerebral Hemorrhage
Oral Anticoagulants
Antiplatelet Agents
Recombinant Activated Factor VII
Lead sponsor: University Of Perugia
Sponsor class: OTHER
First posted: 2005-09-22
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Evaluation of efficacy and safety of recombinant factor VIIa versus standard therapy in preventing early haematoma growth in spontaneous acute intracerebral haemorrhage in patients treated with oral anticoagulants or antiplatelets agents

Detailed description: Intracerebral hemorrhage (ICH) is the deadliest, most disabling, and least treatable form of stroke. Approximately 40% of patients die within 1 month of ICH onset, and two-thirds of survivors never regain functional independence. Though guidelines for supportive care exist, there is currently no treatment that has been shown in a randomized-controlled trial to definitely improve outcome after ICH. Hematoma volume is a critical determinant of mortality and functional outcome after ICH, and early hematoma growth may be an important cause of early neurological deterioration.

Considerable clinical interest has been given to the relationship between antiplatelet and antithrombotic treatment and ICH.

The reported incidence of major bleeding events in patients undergoing antithrombotic treatment is 5-11/1,000 patients/year, while the overall range of hemorrhages is about 62/1,000 patients/year.In the patients treated with antithrombotic drugs (oral anticoagulants or antiplatelets agent) the incidence rate of ICH has been shown higher than in the general population. Moreover, the mortality rate for both spontaneous and post-traumatic events is higher in antithrombotic treated patients than in controls. \[14,15\] rFVIIa has been successfully used to control ICH in patients with hemophilia or other coagulation disorders, and can arrest intraoperative bleeding and reverse coagulopathies in patients undergoing neurosurgical procedures.\[19\] rFVIIa has also been reported to prevent or minimize refractory bleeding in non-coagulopathic patients.

Eligibility criteria: Inclusion Criteria:

* ICH in patient on treatment with one of the following:
* a)oral anticoagulant (INR upper than 1,4 at enrollment
* b) aspirin, whatever dosage
* Male or female subjects, age \> 18 years.
* Informed consent

Exclusion Criteria:

* INR below 1.4 for patients on oral anticoagulants.
* Patients with secondary ICH related to infarction, tumor, cerebrovenous thrombosis, thrombolysis.
* Planned neurosurgical intervention.
* Any history of haemophilia or other congenital or acquired coagulopathy requiring specific antihemorrhagic treatment.
* Acute myocardial ischaemia or acute thrombotic stroke (within one year).
* Septicemia, intravascular disseminated coagulation.
* Pregnancy.
* Limb amputation due to vascular disease or claudication within last 30 days.
* Known or suspected allergy to the trial product or related products.
* Participation in other trials within the previous year.

Primary outcomes:
measure: EFFICACY: change in ICH volume from prior to dosing to 24 hours
measure: SAFETY: occurrence of clinical adverse events (Thromboembolic events, death)
Secondary outcomes:
measure: Difference between groups on the modified Rankin Scale, the Barthel Index (BI), the Extended Glasgow Scale (EGCS), and the National Institute of Health's Stroke Scale (NIHSS) at one and three month follow up
Other outcomes:
Locations:
city: Caserta
country: Italy
facility: A.O.R.N. San Sebastiano
city: Forli
country: Italy
facility: Emergency Room
city: Genua
country: Italy
facility: Emergency Department - S.Martino Hospital
city: Messina
country: Italy
facility: Emergency Room - University of Messina
city: Perugia
country: Italy
facility: Internal and Vascular Medicine - Stroke Unit - University of Perugia
city: Piacenza
country: Italy
facility: Divisione di Neurologia
city: Ravenna
country: Italy
facility: Emergency Room
city: Reggio Emilia
country: Italy
facility: Emergency Room
city: Rome
country: Italy
facility: Stroke Unit - Policlinico Universitario Umberto I
Study officials:
affiliation: University Of Perugia
name: Alfonso Iorio
role: PRINCIPAL_INVESTIGATOR
References:
citation: Iorio A. Iatrogenic causes of an ICH: OAT therapy. Eur J Anaesthesiol Suppl. 2008;42:8-11. doi: 10.1017/S0265021507003171.