Individually Tailored Prophylaxis in Patients With Severe Hemophilia A

NCT00995046 | Terminated DMC

• 1 other identifier: 2007.482
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Hemophilia A

Keywords

Hemophilia A; prophylaxis; thrombin generation test (TGT)

Outcome Measures

Primary Outcomes (1)

• Consumption of clotting factor concentrate

  13 months

Secondary Outcomes (2)

• Number of spontaneous bleeds

  13 months

• Number of spontaneous joint bleeds

  13 months

Study Arms (2)

usual prophylaxis regimen

ACTIVE COMPARATOR

All patients will receive their usual prophylaxis regimen during the first 6 months

Drug: FVIII

individually tailored prophylaxis regimen

EXPERIMENTAL

All patients will receive an individually tailored prophylaxis regimen in accordance with TGT results during the second 6 month-period.

Drug: FVIII

Interventions

FVIII DRUG

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.

usual prophylaxis regimen

Eligibility Criteria

• Age: 6 Years - 45 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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
• Presence of a documented target joint

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Hopital Edouard Herriot

Lyon, 69437, France

Location

MeSH Terms

Conditions

Hemophilia A

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Yesim Dargaud, MD, PhD

  Hospices Civils de Lyon, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2009
• First Posted: October 14, 2009
• Study Start: September 1, 2009
• Primary Completion: September 1, 2012
• Last Updated: May 14, 2013

Record last verified: 2009-10

Locations

FR (1)