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

Phase 4

Completed

• Conditions: Hemophilia A
• Interventions: Drug: rFVIIa-FEIBA therapy for hemophilia A inhibitors; Drug: FEIBA- Activated Prothrombin Complexes

• Registration Number: NCT00284193
• Lead Sponsor: Sheba Medical Center

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 Timeline

• Study Start: 2005-01
• Study First Submitted: 2006-01-17
• Study First Submitted QC: 2006-01-29
• Study First Posted: 2006-01-31
• Primary Completion: 2008-11
• Study Completion: 2009-11
• Status Verified: 2012-07
• Last Update Submitted: 2012-07-26
• Last Update Posted: 2012-07-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 5

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
feiba-VIIa, hemophilia A-inhibitor therapy	rFVIIa-FEIBA therapy for hemophilia A inhibitors	COMBINED PATIENT- TAILORED THERAPY WITH CONCOMITANT ADMINISTRATION OF BOTH DRUGS , FOLLOWING EX VIVO THROMBIN GENERATION PREDICTING ASSAYS
feiba-VIIa, hemophilia A-inhibitor therapy	FEIBA- Activated Prothrombin Complexes	COMBINED PATIENT- TAILORED THERAPY WITH CONCOMITANT ADMINISTRATION OF BOTH DRUGS , FOLLOWING EX VIVO THROMBIN GENERATION PREDICTING ASSAYS

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Time to Hemostasis	0-24 HOURS	Following therapy patients documented time to "GOOD" response