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

NCT00284193 | Completed Phase 4

• 1 other identifier: SHEBA-05-3768-UM-CTIL
• Study Type: interventional
• Target: 5
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Hemophilia A

Outcome Measures

Primary Outcomes (2)

• Hemostasis achieved post therapy

  Following acute bleeding therapy hemostasis was defined as good, partial or non-satisfactory

  6-24 hours

• Safety

  Following therapy presence of any adverse events, especially thromboembolic complications was assessed

  0-24 HOURS

Secondary Outcomes (1)

• Time to Hemostasis

  0-24 HOURS

Other Outcomes (1)

• Coagulation Studies

  0-24 HOURS

Study Arms (1)

feiba-VIIa, hemophilia A-inhibitor therapy

EXPERIMENTAL

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; Drug: FEIBA- Activated Prothrombin Complexes

Interventions

rFVIIa-FEIBA therapy for hemophilia A inhibitors DRUG

DOses tailored per ex vivo spiking thrombin generation

Also known as: NOVOSEVEN, APCC

feiba-VIIa, hemophilia A-inhibitor therapy

FEIBA- Activated Prothrombin Complexes DRUG

feiba-VIIa, hemophilia A-inhibitor therapy

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Hemophilia patients with inhibitors
• Patients signing informed consent

You may not qualify if:

• Patients under 16 or above 65
• Patients with allergic reaction or adverse events in previous use the concentrates
• Patients with high risk of thrombosis

Sponsors & Collaborators

• Sheba Medical Center: lead

MeSH Terms

Conditions

Hemophilia A

Interventions

recombinant FVIIa

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Uri Martinowitz, MD

  Sheba Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Uri Martinowitz

Study Record Dates

• First Submitted: January 17, 2006
• First Posted: January 31, 2006
• Study Start: January 1, 2005
• Primary Completion: November 1, 2008
• Study Completion: November 1, 2009
• Last Updated: July 27, 2012

Record last verified: 2012-07