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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
  Purpose

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.


Condition Intervention Phase
Hemophilia A
 Drug: rFVIIa-FEIBA therapy for hemophilia A inhibitors
Drug: FEIBA- Activated Prothrombin Complexes
 Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Combination Therapy of Low Doses of rFVIIa and FEIBA for Severe Hemophilia A Patients With an Inhibitor to Factor VIII

Resource links provided by NLM:

MedlinePlus related topics: Hemophilia
U.S. FDA Resources

Further study details as provided by Sheba Medical Center:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • Time to Hemostasis [ Time Frame: 0-24 HOURS ] [ Designated as safety issue: No ]
    Following therapy patients documented time to "GOOD" response


Other Outcome Measures:
  • 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


Enrollment: 5
Study Start Date: January 2005
Study Completion Date: November 2009
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: feiba-VIIa, hemophilia A-inhibitor therapy
COMBINED PATIENT- TAILORED THERAPY WITH CONCOMITANT ADMINISTRATION OF BOTH DRUGS , FOLLOWING EX VIVO THROMBIN GENERATION PREDICTING ASSAYS
 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

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.

  Eligibility

Ages Eligible for Study:   16 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00284193

Sponsors and Collaborators
Sheba Medical Center
Investigators
Principal Investigator: Uri Martinowitz, MD Sheba Medical Center
  More Information

No publications provided

Responsible Party: Prof. Uriel Martinowitz, Prof. Uri Martinowitz, Sheba Medical Center
ClinicalTrials.gov Identifier: NCT00284193     History of Changes
Other Study ID Numbers: SHEBA-05-3768-UM-CTIL
Study First Received: January 17, 2006
Last Updated: July 26, 2012
Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration

Additional relevant MeSH terms:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
 Factor VIII
Thrombin
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Hemostatics

ClinicalTrials.gov processed this record on May 16, 2013