Brief Title
Combination Therapy of Low Doses of rFVIIa and FEIBA for Severe Hemophilia A Patients With an Inhibitor to Factor VIII
Official Title
Combination Therapy of Low Doses of rFVIIa and FEIBA for Severe Hemophilia A Patients With an Inhibitor to Factor VIII
Brief Summary
Patients with severe hemophilia and inhibitors can be treated effectively by Activated Prothrombin Complex Concentrates (APCC, eg. FEIBA) or High dose recombinant factor VIIa (rFVIIa). Rarely, such patients develop refractoriness to these products for whom therapy with sequential FEIBA and rFVIIa has been recently suggested. The impetus for the present report was a hemophilia A patient with high titer inhibitor (1300BU) who had life threatening hematuria that was resistant to repeated doses of 400µg/kg rFVIIa up to a cumulative dose of 1200 µg/kg given over 6-9 hours. Thrombin generation (TG) tested in vitro was consistent with resistance to high concentrations of rFVIIa but yielded good response to combinations of low doses of rFVIIa+FEIBA. In a desperate attempt to control the bleeding, concomitant therapy of 25 U/kg FEIBA and 40µg/kg rFVIIa was infused and resulted in arrest of bleeding within minutes. Over a span of about one year the patient has been successfully treated by this combination for more than 200 bleeding episodes in muscles and joints.
Detailed Description
Inhibitor patients with HR inhibitors were eligible for study enrollment. After consent blood was drawn and ex- vivo spiked with rFVIIa/FEIBA and combinations, assayed by thrombin generation tests. The combination yielding sufficient hemostasis was depicted for patients' therapy of future bleeding episodes. Following actual therapy hemostasis and safety parameters were monitored.
Study Phase
Phase 4
Study Type
Interventional
Primary Outcome
Hemostasis achieved post therapy
Secondary Outcome
Time to Hemostasis
Condition
Hemophilia A
Intervention
rFVIIa-FEIBA therapy for hemophilia A inhibitors
Study Arms / Comparison Groups
feiba-VIIa, hemophilia A-inhibitor therapy
Description: COMBINED PATIENT- TAILORED THERAPY WITH CONCOMITANT ADMINISTRATION OF BOTH DRUGS , FOLLOWING EX VIVO THROMBIN GENERATION PREDICTING ASSAYS
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
5
Start Date
January 2005
Completion Date
November 2009
Primary Completion Date
November 2008
Eligibility Criteria
Inclusion Criteria: - Hemophilia patients with inhibitors - Patients signing informed consent Exclusion Criteria: - Patients under 16 or above 65 - Patients with allergic reaction or adverse events in previous use the concentrates - Patients with high risk of thrombosis
Gender
Male
Ages
16 Years - 65 Years
Accepts Healthy Volunteers
No
Contacts
Uri Martinowitz, MD, ,
Administrative Informations
NCT ID
NCT00284193
Organization ID
SHEBA-05-3768-UM-CTIL
Responsible Party
Principal Investigator
Study Sponsor
Sheba Medical Center
Study Sponsor
Uri Martinowitz, MD, Principal Investigator, Sheba Medical Center
Verification Date
July 2012