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

Hemophilia A Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00284193
• Other study ID #: SHEBA-05-3768-UM-CTIL
• Status: Completed
• Phase: Phase 4
• First received: January 17, 2006
• Last updated: July 26, 2012
• Start date: January 2005
• Est. completion date: November 2009

Study information

• Verified date: July 2012
• Source: Sheba Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Israeli Health Ministry Pharmaceutical Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: November 2009
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 16 Years to 65 Years

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hemophilia A

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sheba Medical Center

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Coagulation Studies	cbc fibrinogen and D-dimer were assessed pre and post therapy, thrombin generation was assayed when possible after 1-2 hours	0-24 HOURS	Yes
Primary	Hemostasis achieved post therapy	Following acute bleeding therapy hemostasis was defined as good, partial or non-satisfactory	6-24 hours	No
Primary	Safety	Following therapy presence of any adverse events, especially thromboembolic complications was assessed	0-24 HOURS	Yes
Secondary	Time to Hemostasis	Following therapy patients documented time to "GOOD" response	0-24 HOURS	No