Combination Therapy of Low Doses of rFVIIa and FEIBA for Severe Hemophilia A Patients With an Inhibitor to Factor VIII
|ClinicalTrials.gov Identifier: NCT00284193|
Recruitment Status : Completed
First Posted : January 31, 2006
Last Update Posted : July 27, 2012
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.
|Condition or disease||Intervention/treatment||Phase|
|Hemophilia A||Drug: rFVIIa-FEIBA therapy for hemophilia A inhibitors Drug: FEIBA- Activated Prothrombin Complexes||Phase 4|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||5 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Combination Therapy of Low Doses of rFVIIa and FEIBA for Severe Hemophilia A Patients With an Inhibitor to Factor VIII|
|Study Start Date :||January 2005|
|Actual Primary Completion Date :||November 2008|
|Actual Study Completion Date :||November 2009|
U.S. FDA Resources
Experimental: feiba-VIIa, hemophilia A-inhibitor therapy
COMBINED PATIENT- TAILORED THERAPY WITH CONCOMITANT ADMINISTRATION OF BOTH DRUGS , FOLLOWING EX VIVO THROMBIN GENERATION PREDICTING ASSAYS
Drug: rFVIIa-FEIBA therapy for hemophilia A inhibitors
DOses tailored per ex vivo spiking thrombin generation
Other Names:Drug: FEIBA- Activated Prothrombin Complexes
- Hemostasis achieved post therapy [ Time Frame: 6-24 hours ]Following acute bleeding therapy hemostasis was defined as good, partial or non-satisfactory
- Safety [ Time Frame: 0-24 HOURS ]Following therapy presence of any adverse events, especially thromboembolic complications was assessed
- Time to Hemostasis [ Time Frame: 0-24 HOURS ]Following therapy patients documented time to "GOOD" response
- Coagulation Studies [ Time Frame: 0-24 HOURS ]cbc fibrinogen and D-dimer were assessed pre and post therapy, thrombin generation was assayed when possible after 1-2 hours
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00284193
|Principal Investigator:||Uri Martinowitz, MD||Sheba Medical Center|