Individually Tailored Prophylaxis in Patients With Severe Hemophilia A

Hemophilia A Clinical Trial

— OPTIPHASE  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00995046
• Other study ID #: 2007.482
• Status: Terminated
• Phase: N/A
• First received: October 12, 2009
• Last updated: May 13, 2013
• Start date: September 2009

Study information

• Verified date: October 2009
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 6 Years to 45 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Hemophilia A

Intervention

Drug:
• FVIII
6 months of prophylaxis treatment administered 3 or 4 times weekly according to patient's initial regimen, (standardized Malmö protocol 25 - 40 IU/kg/infusion). Medical visits will occur at 3-month intervals (+ 5 days) until the end of the study. Weekly, telephone calls to the patients (parents) will also be done.
• FVIII
1 month period where thrombin generating capacity will be evaluated, followed by 6 months of "individually" tailored prophylaxis regimen according to TGT results. Medical visits will occur at 3-month intervals (+ 5 days) until the end of the study. Weekly, telephone calls to the patients (parents) will also be done.

Locations

Country	Name	City	State
France	Hopital Edouard Herriot	Lyon

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Consumption of clotting factor concentrate		13 months	Yes
Secondary	Number of spontaneous bleeds		13 months	Yes
Secondary	Number of spontaneous joint bleeds		13 months	Yes