Individually Tailored Prophylaxis in Patients With Severe Hemophilia A (OPTIPHASE)

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

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 Overview

• Status: Terminated
• Conditions: Hemophilia A
• Intervention / Treatment: Drug: FVIII; Drug: FVIII

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69437
    • Hôpital Edouard Herriot

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: usual prophylaxis regimen; All patients will receive their usual prophylaxis regimen during the first 6 months	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.; Drug: 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.
Experimental: individually tailored prophylaxis regimen; All patients will receive an individually tailored prophylaxis regimen in accordance with TGT results during the second 6 month-period.	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.; Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Consumption of clotting factor concentrate	13 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of spontaneous bleeds	13 months
Number of spontaneous joint bleeds	13 months

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Yesim Dargaud, MD, PhD, Hospices Civils de Lyon, France

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: October 12, 2009
• First Submitted That Met QC Criteria: October 13, 2009
• First Posted (Estimate): October 14, 2009

Study Record Updates

• Last Update Posted (Estimate): May 14, 2013
• Last Update Submitted That Met QC Criteria: May 13, 2013
• Last Verified: October 1, 2009

More Information

Terms related to this study

• Keywords: prophylaxis; Hemophilia A; thrombin generation test (TGT)
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A; Coagulants; Factor VIII
• Other Study ID Numbers: 2007.482