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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Prof. Uriel Martinowitz, Sheba Medical Center
ClinicalTrials.gov Identifier:
NCT00284193
First received: January 17, 2006
Last updated: July 26, 2012
Last verified: July 2012
History of Changes

January 17, 2006
July 26, 2012
January 2005
November 2008   (final data collection date for primary outcome measure)
  • Hemostasis achieved post therapy [ Time Frame: 6-24 hours ] [ Designated as safety issue: No ]
    Following acute bleeding therapy hemostasis was defined as good, partial or non-satisfactory
  • Safety [ Time Frame: 0-24 HOURS ] [ Designated as safety issue: Yes ]
    Following therapy presence of any adverse events, especially thromboembolic complications was assessed
Not Provided
Complete list of historical versions of study NCT00284193 on ClinicalTrials.gov Archive Site
Time to Hemostasis [ Time Frame: 0-24 HOURS ] [ Designated as safety issue: No ]
Following therapy patients documented time to "GOOD" response
Not Provided
Coagulation Studies [ Time Frame: 0-24 HOURS ] [ Designated as safety issue: Yes ]
cbc fibrinogen and D-dimer were assessed pre and post therapy, thrombin generation was assayed when possible after 1-2 hours
Not Provided
 
Combination Therapy of Low Doses of rFVIIa and FEIBA for Severe Hemophilia A Patients With an Inhibitor to Factor VIII
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.

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.
Interventional
Phase 4
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Hemophilia A
  • Drug: rFVIIa-FEIBA therapy for hemophilia A inhibitors
    DOses tailored per ex vivo spiking thrombin generation
    Other Names:
    • NOVOSEVEN
    • APCC
  • Drug: FEIBA- Activated Prothrombin Complexes
Experimental: feiba-VIIa, hemophilia A-inhibitor therapy
COMBINED PATIENT- TAILORED THERAPY WITH CONCOMITANT ADMINISTRATION OF BOTH DRUGS , FOLLOWING EX VIVO THROMBIN GENERATION PREDICTING ASSAYS
Interventions:
  • Drug: rFVIIa-FEIBA therapy for hemophilia A inhibitors
  • Drug: FEIBA- Activated Prothrombin Complexes
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
5
November 2009
November 2008   (final data collection date for primary outcome measure)

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
Male
16 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00284193
SHEBA-05-3768-UM-CTIL
No
Prof. Uriel Martinowitz, Sheba Medical Center
Sheba Medical Center
Not Provided
Principal Investigator: Uri Martinowitz, MD Sheba Medical Center
Sheba Medical Center
July 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP