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

Sheba Medical Center

Status and phase: Completed; Phase 4

Conditions: Hemophilia A

Treatments: Drug: FEIBA- Activated Prothrombin Complexes; Drug: rFVIIa-FEIBA therapy for hemophilia A inhibitors

Study type: Interventional

Funder types: Other

Identifiers

NCT00284193

SHEBA-05-3768-UM-CTIL

Details and patient eligibility

About

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.

Full 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.

Enrollment: 5 patients

Sex: Male

Ages: 16 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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5 participants in 1 patient group

feiba-VIIa, hemophilia A-inhibitor therapy

Experimental group

Description:

COMBINED PATIENT- TAILORED THERAPY WITH CONCOMITANT ADMINISTRATION OF BOTH DRUGS , FOLLOWING EX VIVO THROMBIN GENERATION PREDICTING ASSAYS

Treatment:

Drug: FEIBA- Activated Prothrombin Complexes

Drug: rFVIIa-FEIBA therapy for hemophilia A inhibitors