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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00995046
Recruitment Status : Terminated
First Posted : October 14, 2009
Last Update Posted : May 14, 2013
Information provided by (Responsible Party):
Hospices Civils de Lyon

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.

Condition or disease Intervention/treatment Phase
Hemophilia A Drug: FVIII Not Applicable

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
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
Study Start Date : September 2009
Actual Primary Completion Date : September 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia
Drug Information available for: Thrombin
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: usual prophylaxis regimen
All patients will receive their usual prophylaxis regimen during the first 6 months
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.
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.
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.

Primary Outcome Measures :
  1. Consumption of clotting factor concentrate [ Time Frame: 13 months ]

Secondary Outcome Measures :
  1. Number of spontaneous bleeds [ Time Frame: 13 months ]
  2. Number of spontaneous joint bleeds [ Time Frame: 13 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years to 45 Years   (Child, Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00995046

Hopital Edouard Herriot
Lyon, France, 69437
Sponsors and Collaborators
Hospices Civils de Lyon
Principal Investigator: Yesim Dargaud, MD, PhD Hospices Civils de Lyon - France

Responsible Party: Hospices Civils de Lyon Identifier: NCT00995046     History of Changes
Other Study ID Numbers: 2007.482
First Posted: October 14, 2009    Key Record Dates
Last Update Posted: May 14, 2013
Last Verified: October 2009

Keywords provided by Hospices Civils de Lyon:
Hemophilia A
thrombin generation test (TGT)

Additional relevant MeSH terms:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII