Individually Tailored Prophylaxis in Patients With Severe Hemophilia A (OPTIPHASE)
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 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|
- Consumption of clotting factor concentrate [ Time Frame: 13 months ] [ Designated as safety issue: Yes ]
- 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 ]
|Study Start Date:||September 2009|
|Primary Completion Date:||September 2012 (Final data collection date for primary outcome measure)|
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00995046
|Hopital Edouard Herriot|
|Lyon, France, 69437|
|Principal Investigator:||Yesim Dargaud, MD, PhD||Hospices Civils de Lyon - France|