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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon
ClinicalTrials.gov Identifier:
NCT00995046
First received: October 12, 2009
Last updated: May 13, 2013
Last verified: October 2009
  Purpose

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 Intervention
Hemophilia A
Drug: FVIII

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Hospices Civils de Lyon:

Primary Outcome Measures:
  • Consumption of clotting factor concentrate [ Time Frame: 13 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of spontaneous bleeds [ Time Frame: 13 months ] [ Designated as safety issue: Yes ]
  • Number of spontaneous joint bleeds [ Time Frame: 13 months ] [ Designated as safety issue: Yes ]

Enrollment: 5
Study Start Date: September 2009
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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.

  Eligibility

Ages Eligible for Study:   6 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00995046

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

No publications provided

Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT00995046     History of Changes
Other Study ID Numbers: 2007.482
Study First Received: October 12, 2009
Last Updated: May 13, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Hospices Civils de Lyon:
Hemophilia A
prophylaxis
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
Thrombin
Factor VIII
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 19, 2014