Individually Tailored Prophylaxis in Patients With Severe Hemophilia A

Brief Title

Individually Tailored Prophylaxis in Patients With Severe Hemophilia A

Official Title

Optimizing Prophylaxis in Patients With Severe Haemophilia A by Tailoring the Infusions to Individual Patients' Needs Using the Calibrated Automated Thrombin Generation Test

Brief Summary

Patients with severe haemophilia A lack clotting factor FVIII and suffer from spontaneous and
traumatic bleeds. In the absence of treatment, frequent bleeds in joints lead to severe joint
destruction. In 1960s, prophylactic therapy was developed involving the infusion of clotting
factor on a regular schedule in order to keep clotting levels sufficiently high to prevent
spontaneous bleeding episodes. Prophylaxis is started at an early age before the age of 2
years or after the first joint bleed. The Malmö experience indicates that treatment is most
effective when administered in large doses at least 3 times weekly. However, such an
intensive treatment in young boys may be very difficult to carry out for home treatment.
Currently, there is no international recommendation on prophylactic therapy regimens. Because
of the high cost and limited availability of factor concentrates, dosing is an important
issue in prophylaxis therapy. It was recently shown that 24 hours after FVIII concentrate
administration, in patients presenting similar FVIIII levels, thrombin generation capacity
may be significantly different. In addition, independently of the FVIII level, a correlation
was found between severe clinical bleeding phenotype and thrombin generating capacity. The
aim of the present clinical study is to assess the thrombin generation test as the main
surrogate marker to evaluate the coagulating capacity of haemophiliacs on prophylaxis
regimen. Optimizing prophylactic therapy to patient's phenotype with no loss of clinical
effectiveness can significantly improve patients' quality of life, protect haemophilic
children against arthropathy and possibly limit the cost of the prophylaxis therapy.

Study Type

Interventional

Primary Outcome

Consumption of clotting factor concentrate

Secondary Outcome

 Number of spontaneous bleeds

Condition

Hemophilia A

Intervention

FVIII

Study Arms / Comparison Groups

 usual prophylaxis regimen

Description:  All patients will receive their usual prophylaxis regimen during the first 6 months

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Drug

Estimated Enrollment

Start Date

September 2009

Primary Completion Date

September 2012

Eligibility Criteria

        Inclusion Criteria:

          -  Severe haemophilia A (FVIII < 1 IU/dl)

          -  Currently on prophylactic therapy administered at least 3 times per week with a
             clinical efficiency

          -  Age: 6 - 45 years

          -  Adequate venous access in adults and children i.e. presence of 2 or more good quality
             peripheral veins, in order to avoid the need for a central venous device. One
             peripheral vein for FVIII infusions and one other for blood sampling are required.

          -  Competent in home treatment and infusion therapy (patient or parents)

          -  Ability of patient or family (for minors) to give informed consent

          -  Patient affiliated to French Social Insurance System.

        Exclusion Criteria:

          -  Age < 6 years and > 45 years

          -  Hemophilia A with documented history of inhibitor

          -  Clinically symptomatic liver disease (supported by e.g. diagnosis of cirrhosis, portal
             hypertension, ascites, PT > 5 seconds above upper limit of normal)

          -  Platelet count < 100x109/l

          -  Planned elective surgery within 13 months

          -  Poor venous access according inclusion criteria

          -  Presence of a documented target joint

Gender

Male

Ages

6 Years - 45 Years

Accepts Healthy Volunteers

No

Contacts

Yesim Dargaud, MD, PhD, ,

Location Countries

France

Location Countries

France

Administrative Informations

NCT ID

NCT00995046

Organization ID

2007.482

Responsible Party

Sponsor

Study Sponsor

Hospices Civils de Lyon

Study Sponsor

Yesim Dargaud, MD, PhD, Principal Investigator, Hospices Civils de Lyon - France

Verification Date

October 2009