Personalized Prophylactic Treatment With Advate® in Severe or Moderate Haemophilia A Patients

• Status: Unknown status
• Trial end date: 2018-02-01
• Target enrollment: 0
• Participant gender: All

Summary

Haemophilia A is an inherited bleeding disorder caused by a deficiency of factor VIII (FVIII). Patients with severe hemophilia A have a FVIII plasma concentration less than1 IU/dL and experience spontaneous and trauma-induced bleeds. Joint bleeds lead to hemophilic arthropathy resulting in progressive disability. Patients with moderate hemophilia (FVIII level between 1-5 IU/dL) are characterized by fewer hemarthroses, usually trauma-induced, and a decreased likelihood of developing arthropathy. This clinical observation led to the use of prophylactic FVIII infusions to convert patient´s bleeding phenotype from severe to moderate with the result of decreasing or preventing arthropathy.

Prophylactic regimens may be effective when based on standard fixed-dose protocols (that assumes one approach fits all patients) or phenotypic dosing determined by bleeding patterns, but do not protect all patients with severe haemophilia from joint damage caused by spontaneous or activity-triggered bleeding.

Individualized treatment in haemophilia A takes into consideration all available information about the patient, not only his phenotypic bleeding pattern. Some of the factors that contribute to the observed interpatient variability include baseline or residual FVIII activity, the pharmacokinetic (PK) profile of the replacement factor, the individual's level of physical activity and perceived risk of traumatic bleeding, the presence or absence of joint disease, presence of comorbidities and adherence to the dosing regimen.

Objectives:

Identify and analyze cause(s) of poor bleeding control in patients on prophylaxis treatment and study the clinical impact of a "personalized pilot program" with a 1 year follow up to act on the specific causes.

1. Describe PK parameters in patients on prophylaxis treatment with Advate®.

2. Analyze differences in PK parameters in non-controlled vs well controlled patients.

3. Identify causes of poor clinical outcome in non-controlled patients. Patients' individual variables that influence bleeding risk will be studied (individual PK, bleeding pattern, joint status, physical activity, life style and patient's adherence).

4. Study the improvement in clinical outcomes (ABR and Joint status) of a 1 year Personalized Prophylaxis Program that acts specifically on the previously identified causes of bleeding in non-controlled patients (named: short half-life, high bleeding pattern, joint damage, high risk physical activity, active life style and poor patient's adherence).

• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hospital Universitario La Fe
• Treatments: Factor VIII

Criteria

Inclusion Criteria:

• Adults or adolescents older than 12 years

• Patients under Prophylactic treatment with Advate® for at least 1 year

• Written informed consent.

Exclusion Criteria:

• History of FVIII inhibitor (titre ≥ 0.6 BU [Bethesda unit]) or detectable FVIII inhibitors at screening (titre ≥ 0.4 BU),

• Another haemostatic defect

• Need for major surgery.

• Withdrawal of informed consent