View clinical trials related to Von Willebrand Diseases.
Filter by:Primary Objective: -To characterize the pharmacokinetics (PK) of BIVV001 after a single intravenous (IV) administration, as assessed by factor VIII (FVIII) activity determined by the one-stage activated partial thromboplastin time (aPPT) clotting assay, as well as, BIVV001 capture chromogenic Coatest FVIII activity assay Secondary Objective: -To assess the safety and tolerability of a single IV dose of BIVV001 in adult patients with type 2N and 3 VWD
BT200 is a PEGylated aptamer that binds to the A1 domain of human von Willebrand factor (VWF). At low doses, BT200 blocks the clearance of VWF antigen (VWF Ag) from the circulation and causes an increase in concentrations of both VWF Ag and Factor VIII (FVIII), but has negligible effect on the activity of either. At higher doses, BT200 blocks clearance of VWF and also inhibits its activity, but still does not inhibit FVIII activity. Therefore, low dose BT200 could potentially be used to correct deficiency of VWF and/or FVIII in patients with hereditary bleeding disorders. This study is designed as a "basket design" pilot study to determine the relevant dose and pharmacological activity of BT200 in such patients. In this open basket study up to 25 patients with the following congenital blood-clotting disorders are to be included: Patients with hemophilia A, heterozygous carriers of hemophilia A with subnormal FVIII levels; patients with von Willebrand syndrome (VWD) type 1, "Vicenza type", and with VWD type 2b. Participants will receive BT200 subcutaneously on day 0, day 4 and day 7 in the first week and then once a week for a total of five weeks - initially in a dose of 3 mg, then in week 3 individually after response in a dose of 3 to 9 mg. Subsequently, blood samples are taken once a week for a further three weeks (wash-out phase). Patients may be enrolled in an additional pharmacokinetics sub-study. For this purpose, approximately three blood samples are taken to estimate the half-life of substituted FVIII under the influence of BT200. The primary objective of this study is to obtain clinical proof of mechanism for BT200 in one or more hereditary bleeding disorders.
Description of the long-term evolution of patients with von Willebrand disease and treated with Voncento® and of the hemostatic efficacy in the prevention and the treatment of non-surgical bleeding episodes and prevention of surgical bleeding during 2 years after patient inclusion.
Inclusion criteria: Only constitutional VWD-patients fulfilling the inclusion criteria of the French reference center for VWD will be included. Patients with acquired von Willebrand syndrome will not be included. Material and Methods: A 15-items survey that will be sent to the 30 centers involved in the French network for bleeding disorders (MHEMO) to identify VWD-patients referred for endoscopic exploration of at least one GI-bleeding from January 2015 to December 2017. Only constitutional VWD-patients fulfilling the inclusion criteria of the French reference center for VWD will be included. Constitutional VWD diagnosis will be confirmed confirmed centrally in all patients by the French reference center for von Willebrand disease. A GI-bleeding episode will be defined as any overt or occult GI-bleeding (unexplained chronic iron deficiency anemia causing a drop of hemoglobin level by more than 2 g/dL from baseline). We will analyze patient characteristics, GI-bleeding pattern, VWD type/subtype, nature (gastroscopy, colonoscopy or VCE) and results of the endoscopic exploration and management that was applied: endoscopic therapy by argon plasma coagulation, on-demand/prophylactic-VWF replacement therapy, use of antiangiogenic drugs. If angiodysplasia without another bleeding source is identified, GI-bleeding will be categorized as angiodysplasia, if another lesion is identified GI-bleeding will be categorized as "no-angiodysplasia" and if no bleeding source is identified, GI-bleeding will be categorized as obscure GI-bleeding. Recurrence will be defined as evidence of overt GI-bleeding or a drop of hemoglobin level by more than 2 g/dL from baseline.
In parallel with the growth of American Thrombosis and Hemostasis Network's (ATHN) clinical studies, the number of new therapies for all congenital and acquired hematologic conditions, not just those for bleeding and clotting disorders, is increasing significantly. Some of the recently FDA-approved therapies for congenital and acquired hematologic conditions have yet to demonstrate long-term safety and effectiveness beyond the pivotal trials that led to their approval. In addition, results from well-controlled, pivotal studies often cannot be replicated once a therapy has been approved for general use.(1,2,3,4) In 2019 alone, the United States Food and Drug Administration (FDA) has issued approvals for twenty-four new therapies for congenital and acquired hematologic conditions.(5) In addition, almost 10,000 new studies for hematologic diseases are currently registered on www.clinicaltrials.gov.(6) With this increase in potential new therapies on the horizon, it is imperative that clinicians and clinical researchers in the field of non-neoplastic hematology have a uniform, secure, unbiased, and enduring method to collect long-term safety and efficacy data. ATHN Transcends is a cohort study to determine the safety, effectiveness, and practice of therapies used in the treatment of participants with congenital or acquired non-neoplastic blood disorders and connective tissue disorders with bleeding tendency. The study consists of 7 cohorts with additional study "arms" and "modules" branching off from the cohorts. The overarching objective of this longitudinal, observational study is to characterize the safety, effectiveness and practice of treatments for all people with congenital and acquired hematologic disorders in the US. As emphasized in a recently published review, accurate, uniform and quality national data collection is critical in clinical research, particularly for longitudinal cohort studies covering a lifetime of biologic risk.(7)
This is a single-center randomized phase III clinical trial, the VWD-Woman Trial, in which 20 pregnant subjects with von Willebrand disease (VWD), defined as VWF ristocetin co-factor activity (VWF:RCo) <0.50 IU/ml (historic) and previous history of bleeding are enrolled. Subjects will include women with VWD age 18 years and older, excluding those who have a bleeding disorder other than VWD. Once enrolled, subjects who meet all of the inclusion and none of the exclusion criteria will be randomized to recombinant Von Willebrand factor (rVWF, Vonvendi ®) with Tranexamic Acid (TA, Cyclokapron®); or recombinant Von Willebrand factor (rVWF, Vonvendi®) alone to prevent postpartum hemorrhage after vaginal or caesarean delivery. The primary endpoint is quantitative blood loss (QBL) by a labor suite nurse at delivery. Secondary endpoints include safety assessment for postpartum lochial blood loss by Pictorial Blood Assessment Chart (PBAC), transfusion, blood products, thromboembolic events, and hysterectomy within 21 days; and mechanism of PPH reduction by VWF assays (VWF:RCo, VWF:Ag, VIII:C), fibrinogen, and d-dimer. Blood draws are at 5 time points, including at 36 weeks' gestation (screening), on admission for childbirth, and at 1 day, 2 days, and 21 days after delivery. The VWD-Woman Trial is considered greater than minimal risk as study drugs are given at delivery and special coagulation studies are obtained.
Rationale: Transcatheter aortic valve implantation (TAVI) has become the standard therapy for elderly patients with high surgical risks. Paravalvular leakage after TAVI is relatively common and there is conflicting evidence regarding the clinical impact of mild paravalvular leakage in self-expanding devices. Prospective data for self-expanding devices are required to compare the extent of paravalvular leakage as a result of device design. Grading paravalvular leakage after TAVI is difficult. Echocardiography and angiography systematically underestimate paravalvular leakage (PVL) as compared to cardiac MRI. Hemodynamic measurements are used to aid decision making directly after TAVI implantation. Prospective data comparing hemodynamic measurements with cardiac MRI are needed to design an optimal strategy to grade paravalvular leakage peri-operatively in order to optimize TAVI outcomes. The combination of aortic valve stenosis, angiodysplasia and von Willebrand Disease type 2A (vWD-2A) is known as Heyde syndrome. Previous studies have shown a decrease in angiodysplastic lesions after TAVI. However, since PVL after TAVI is relatively common, angiodysplastic lesions tend to reoccur. Prospective data comparing the severity of PVL to the severity of both vWD-2A and angiodysplasia are lacking. Objective: To assess procedural hemodynamic measurements in patients with paravalvular regurgitation quantified by means of cardiac MRI (CMR) and to analyse its association with impaired clinical outcome during 5-year follow-up. Secondary objectives are to assess whether the severity of vWD-2A correlates with the severity of PVL measured by cardiac MRI, and to prospectively assess the success percentage of TAVI in the treatment of angiodysplasia. Study design: This is a prospective, single-center clinical trial. Patients will receive a TAVI. After implantation different hemodynamic indices of PVL will be assessed. Within 4-8 weeks after TAVI a cardiac MRI will be performed to quantify the amount of PVL. Standardized clinical follow-up will take place at discharge, 30 days, 3 months, 6 months and 1 year. Telephone follow-up will take place at 2, 3, 4 and 5 years after TAVI. In patients with known angiodysplasia or iron deficiency anemia e.c.i., a videocapsule endoscopy (VCE) will take place before TAVI and 6 months after TAVI. Of note, for the substudy on Heyde syndrome, patients with a different type of TAVI valve (i.e. no Abbott Portico valve) are also allowed to participate. Study population: Approximately 80 patients with severe symptomatic aortic valve stenosis with an indication for TAVI will be included. At least 76 patients with a cardiac MRI that is of sufficient quality to quantify the amount of PVL will be included. Intervention: Patients will undergo cardiac MRI on top of standard clinical care within 4-8 weeks after TAVI. A subgroup of patients will also undergo a VCE. Main study parameters/endpoints: The primary endpoint is defined as PVL regurgitation fraction as measured by cardiac MRI. One secondary endpoint will comprise a composite of device success, early safety and clinical efficacy as defined by the Valve Academic Research Consortium-2 (VARC-2) (1) and will comprise death, vascular complications, stroke/TIA, life-threatening bleeding requiring transfusion, and acute kidney injury requiring dialysis. Another secondary endpoint will be the reduction of angiodysplastic lesions after TAVI as determined by VCE. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The hemodynamic indices can be assessed in a standard fashion using a fluid filled pigtail catheter that is placed in the left ventricle as part of the routine protocol. Following TAVI, enrolled patients will undergo cardiac MRI to assess PVL. The risk of cardiac MRI after TAVI implantation is negligible. Extra blood samples will be taken. After one year, patients will be followed by telephonic follow-up. Risk/benefit: the expected benefit is a structured clinical follow-up at 1, 2, 3, 4 and 5 years, at the cost of an extra visit to undergo cardiac MRI.
Establish a Latin-American network of centers and professionals with the aim of: - To register VWD patients in retrospective/prospective study, using a database, available online, common to all - To register the bleeding history, the treatment and the events of VWD patients in the region - To investigate the influence of VWD on quality of life
In pregnant women with von Willebrand disease (VWD) who by the third trimester do not have von Willebrand factor (VWF) or factor VIII (FVIII) levels greater than 50-100%, specific guidance is lacking for delivery planning in terms of how high of a VWF level should be achieved to reduce bleeding. This is a prospective, open-label, cohort study in women with VWD using Wilate VWF replacement therapy to maintain trough or minimum VWF levels of 100-150% for delivery and the immediate postpartum period, followed by levels of 50-100% for 5-10 days after delivery, depending upon the route of delivery. The primary objective is to document the rate of primary postpartum hemorrhage (PPH). The secondary objective is to document further effectiveness outcomes and safety.
In Willebrand disease, there is currently no test available to identify non-invasively patients with a high risk of bleeding from angiodysplasias The study propose to use a sublingual capillary bed analysis by video-microscopy, a sensitive, reproducible and non-invasive technique, to assess whether sublingual capillary density is predictive of hemorrhagic risk for patients with von Willebrand disease.