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

NCT ID: NCT00284193

Last Updated: 2012-07-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-01-31
• Study Completion Date: 2009-11-30

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.

Conditions

Hemophilia A

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

feiba-VIIa, hemophilia A-inhibitor therapy

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

Group Type: EXPERIMENTAL

rFVIIa-FEIBA therapy for hemophilia A inhibitors

Intervention Type: DRUG

DOses tailored per ex vivo spiking thrombin generation

FEIBA- Activated Prothrombin Complexes

Intervention Type: DRUG

Interventions

rFVIIa-FEIBA therapy for hemophilia A inhibitors

DOses tailored per ex vivo spiking thrombin generation

Intervention Type: DRUG

FEIBA- Activated Prothrombin Complexes

Intervention Type: DRUG

Other Intervention Names

NOVOSEVEN; APCC

Eligibility Criteria

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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Sheba Medical Center

OTHER_GOV

Sponsor Role: lead

Responsible Party

Prof. Uriel Martinowitz

Prof. Uri Martinowitz

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Uri Martinowitz, MD

Role: PRINCIPAL_INVESTIGATOR

Sheba Medical Center

Other Identifiers

SHEBA-05-3768-UM-CTIL

Identifier Type: -

Identifier Source: org_study_id