Combination Therapy of Low Doses of rFVIIa and FEIBA for Severe Hemophilia A Patients With an Inhibitor to Factor VIII

Study Overview
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Brief Summary
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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
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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.

Official Title
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Combination Therapy of Low Doses of rFVIIa and FEIBA for Severe Hemophilia A Patients With an Inhibitor to Factor VIII

Conditions
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Hemophilia A

Intervention / Treatment
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* Drug: rFVIIa-FEIBA therapy for hemophilia A inhibitors
* Drug: FEIBA- Activated Prothrombin Complexes


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: feiba-VIIa, hemophilia A-inhibitor therapy<br>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<br>* DOses tailored per ex vivo spiking thrombin generation<br>* Other names: APCC;Drug: FEIBA- Activated Prothrombin Complexes<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemostasis achieved post therapy | Following acute bleeding therapy hemostasis was defined as good, partial or non-satisfactory | 6-24 hours | 
| Safety | Following therapy presence of any adverse events, especially thromboembolic complications was assessed | 0-24 HOURS | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Hemostasis | Following therapy patients documented time to GOOD response | 0-24 HOURS |