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

July 26, 2012 updated by: Prof. Uriel Martinowitz, Sheba Medical Center

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Phase 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hemostasis achieved post therapy
Time Frame: 6-24 hours
Following acute bleeding therapy hemostasis was defined as good, partial or non-satisfactory
6-24 hours
Safety
Time Frame: 0-24 HOURS
Following therapy presence of any adverse events, especially thromboembolic complications was assessed
0-24 HOURS

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Hemostasis
Time Frame: 0-24 HOURS
Following therapy patients documented time to "GOOD" response
0-24 HOURS

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Coagulation Studies
Time Frame: 0-24 HOURS
cbc fibrinogen and D-dimer were assessed pre and post therapy, thrombin generation was assayed when possible after 1-2 hours
0-24 HOURS

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sheba Medical Center

Investigators

  • Principal Investigator: Uri Martinowitz, MD, Sheba medical center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2005

Primary Completion (Actual)

November 1, 2008

Study Completion (Actual)

November 1, 2009

Study Registration Dates

First Submitted

January 17, 2006

First Submitted That Met QC Criteria

January 29, 2006

First Posted (Estimate)

January 31, 2006

Study Record Updates

Last Update Posted (Estimate)

July 27, 2012

Last Update Submitted That Met QC Criteria

July 26, 2012

Last Verified

July 1, 2012

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SHEBA-05-3768-UM-CTIL

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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