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


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.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: November 2008

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.


  • Drug: rFVIIa-FEIBA therapy for hemophilia A inhibitors
    • DOses tailored per ex vivo spiking thrombin generation
  • Drug: FEIBA- Activated Prothrombin Complexes

Arms, Groups and Cohorts

  • Experimental: feiba-VIIa, hemophilia A-inhibitor therapy

Clinical Trial Outcome Measures

Primary Measures

  • 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

Secondary Measures

  • Time to Hemostasis
    • Time Frame: 0-24 HOURS
    • Following therapy patients documented time to “GOOD” response

Participating in This Clinical Trial

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 Eligibility: Male

Minimum Age: 16 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Sheba Medical Center
  • Provider of Information About this Clinical Study
    • Principal Investigator: Prof. Uriel Martinowitz, Prof. Uri Martinowitz – Sheba Medical Center
  • Overall Official(s)
    • Uri Martinowitz, MD, Principal Investigator, Sheba Medical Center

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