View clinical trials related to Hemophilia A.
Filter by:The German Pediatric Hemophilia Research Database will collect data on the prophylactic and therapeutic use of factor concentrates, complications, outcome measures (joint scores, QoL) and living circumstances in newly diagnosed children with hemophilia.
In the context of hemophilia, it is well know that the level of factor VIII alone does not reflect the clinical phenotype of the patients in an accurate way. At equal factor VIII levels, certain patients will bleed more than others. The thrombin generation test (TGT) is a test that seems to provide a better prediction of the overall hemostatic status of an individual patient. In a previous study, the investigators have established normal reference values of the thrombin generation curve in children aged 6 months to 16 years and adults. The goal was to evaluate the use of this test in different clinical contexts and in severe hemophilia patients in particular. A pilot study showed that the patients having a thrombin generation <150 had a severe phenotype, whether those who received an appropriate prophylaxy had a thrombin generation superior to 150. Moreover, the investigators now have access to a software tool that allows them to individually determine the pharmacokinetic profile of the factor VIII injected to each patient. The factor VIII concentration is measured at injection and 30 minutes, 1 hour, 2 hours and 24 hours afterwards. The introduction of these concentrations in the software allows to obtain the half-life of factor for a given patient, the maximum peak, and the minimum factor level (though level). The injected dosis might be sufficient (disappearance of substantial diminution of the bleedings) or unsufficient (persisting bleeding) for a given patient. This study aims: - to measure the pharmacokinetic profile of factor VIII by two different methods, the time-based method and the chromogenic method - to correlate the results with the TGT results obtained at the same time points and determine which method gives the best correlation - to link the clinical symptomatology (improved symptomatology or not) with the TGT results - to determine which minimal TGT result is linked to a minimal bleeding rate - to adapt the prophylactic dosis of the patient in a personalized way.
Haemophilic arthropathy is one of the major complications of severe haemophilia. In order to maintain plasma clotting factor activity levels above 1% and avoid spontaneous joint bleeds and other serious bleeding events, prophylactic factor replacement therapy is used. Because of the high cost and limited availability of clotting factor concentrates, dosing is a crucial issue for prophylaxis therapy. Several studies reported a better correlation between clinical bleeding tendency of patients with haemophilia and thrombin generation assay results compared to FVIII/FIX levels. However there is no specific data showing that thrombin generation may be a better indicator of the clinical efficacy of prophylaxis compared to the conventional FVIII measurement. The main objective of this open, multicentre, prospective study is to compare trough thrombin generation capacity and FVIII levels in severe haemophilia patients and compare these two laboratory results with: - the number of spontaneous haemarthroses and other spontaneous serious bleeds occurred in the last 6 months - the number of additional FVIII units used in the last 6 months This project requires no change in term of type of treatment : During the study, each patient will be treated by his usual clotting factor at the usual regimen (frequency and dosage). The clinical outcome with the usual prophylaxis regimen will be correlated to TGA results
Haemophilia A is an inherited bleeding disorder caused by a deficiency of factor VIII (FVIII). Patients with severe hemophilia A have a FVIII plasma concentration less than1 IU/dL and experience spontaneous and trauma-induced bleeds. Joint bleeds lead to hemophilic arthropathy resulting in progressive disability. Patients with moderate hemophilia (FVIII level between 1-5 IU/dL) are characterized by fewer hemarthroses, usually trauma-induced, and a decreased likelihood of developing arthropathy. This clinical observation led to the use of prophylactic FVIII infusions to convert patient´s bleeding phenotype from severe to moderate with the result of decreasing or preventing arthropathy. Prophylactic regimens may be effective when based on standard fixed-dose protocols (that assumes one approach fits all patients) or phenotypic dosing determined by bleeding patterns, but do not protect all patients with severe haemophilia from joint damage caused by spontaneous or activity-triggered bleeding. Individualized treatment in haemophilia A takes into consideration all available information about the patient, not only his phenotypic bleeding pattern. Some of the factors that contribute to the observed interpatient variability include baseline or residual FVIII activity, the pharmacokinetic (PK) profile of the replacement factor, the individual's level of physical activity and perceived risk of traumatic bleeding, the presence or absence of joint disease, presence of comorbidities and adherence to the dosing regimen. Objectives: Identify and analyze cause(s) of poor bleeding control in patients on prophylaxis treatment and study the clinical impact of a "personalized pilot program" with a 1 year follow up to act on the specific causes. 1. Describe PK parameters in patients on prophylaxis treatment with Advate®. 2. Analyze differences in PK parameters in non-controlled vs well controlled patients. 3. Identify causes of poor clinical outcome in non-controlled patients. Patients' individual variables that influence bleeding risk will be studied (individual PK, bleeding pattern, joint status, physical activity, life style and patient's adherence). 4. Study the improvement in clinical outcomes (ABR and Joint status) of a 1 year Personalized Prophylaxis Program that acts specifically on the previously identified causes of bleeding in non-controlled patients (named: short half-life, high bleeding pattern, joint damage, high risk physical activity, active life style and poor patient's adherence).
The Swiss Hemophilia Registry will collect data on the prophylactic and therapeutic use of factor concentrates in patients with hemophilia and other severe bleeding disorders in Switzerland.
The purpose of this study is to assess the role of a FVIII/VWF complex concentrate (Emoclot) in successfully inducing immune tolerance (I.T.I.) in patients with Haemophilia A with inhibitors, including patients at high risk of failure.
Background The treatment of haemophilia A and B has been revolutionized by the use of factor concentrate, both as prophylaxis and to treat bleeding episodes (on-demand treatment). However, despite its advantages, repeated treatment with factor concentrate can lead to development of inhibitors (antibodies) towards the coagulation factor in the concentrate. Another patient group in which the bleeding symptoms are difficult to treat because of inhibitors towards coagulation factors, most commonly FVIII, is patients with acquired haemophilia. Patients with high antibody titers exhibit a deficient or no response to factor concentrates and usually need treatment with bypassing agents, namely factor eight inhibitor bypassing agent (FEIBA®, Baxter) och recombinant activated factor VII (rFVIIa, Novo-Seven®, Novo Nordisk). The effect of the treatment cannot be accurately monitored by traditional coagulation tests. The aim of the study is to evaluate the utility of the global haemostatic methods in patients with haemophilia with inhibitors. The objective is to improve the monitoring of the treatment effect and thus increase the safety of the patient and the effectiveness of the treatment. Patients and methods Patients The primary cohort will consist of fifteen patients with inherited haemophilia with inhibitors as well as five adult patients with acquired haemophilia who are followed up at the Coagulation Department of the Karolinska University Hospital, Stockholm, Sweden. Blood samples will be collected from those patients at specific time points (see Design of the study) during the course of two years (for each patient). The treatment (type, dose, duration) will be determined by the treating physician. Methods (selection) - Thrombin generation (Calibrated Automated Thrombogram, CAT® and a commercial kit from Siemens®). - Overall haemostatic potential (OHP) Design of the study Timeframe for blood sampling: i) baseline (inclusion in the study), and ii) prior and after administration of bypassing agents to either treat bleeding symptoms or before an invasive procedure or as prophylaxis. Data analysis The variations in coagulation markers measured as described above (Methods) will be associated to the clinical symptoms (bleeding), the level of coagulation factors (if measurable) and the titers of the inhibitors.
Therapy of patients with severe hemophilia (including hemophilia with inhibitors) and other severe bleeding disorders could be monitored and guided based upon special clotting assays , eg thrombin generation and thromboelastography. In this study blood sampled from patients with bleeding disorders will be evaluated applying ex- vivo spiking assays with various coagulation concentrates to potentially address the feasibility of replacement /bypass agents/ combined therapy for future bleeding episodes. Patients that will be further treated by any regimen potentially suggested (as standard care- not within trial) will be thereafter followed , including repeated lab studies to assess the impact of therapy upon hemostasis.
This trial is designed to assess if there is evidence of subclinical joint bleeding on MRI/X-Ray in adults with severe Haemophilia A while on standard and/or pharmacokinetically tailored prophylaxis regimens. Participants with severe Haemophilia A will have longitudinal MRI and XRay imaging of their elbows, ankles and knees at 0, 6 and 18 months while on standard ( 0-6 months) and then pharmacokinetically tailored (7-18 months) recombinant Factor VIII prophylaxis.
This research program is initiated to evaluate and document data on the success of ITI in 300 haemophilia A patients with newly developed or already existing FVIII-inhibitors (also patients who might potentially have failed in earlier ITIs), which will be treated with ITI - preferably high-dose based on individualized product selection, in order to improve management of this potentially devastating complication of haemophilia treatment. In order to investigate the role of in vitro tests on individual ITI success rate in patients undergoing ITI, the inhibitor plasma samples can be assayed against different FVIII concentrates using the following in vitro tests: Batch selection, Thrombin generation assay (TGA), Thrombin Generation Test (TGT) to monitor FVIII efficacy, Epitope mapping,IgG Subclasses specific for FVIII, Immunogenotyping.