Type 3 Von Willebrand International Registries Inhibitor Prospective Study (3WINTERS-IPS)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02460458|
Recruitment Status : Unknown
Verified April 2016 by Fondazione Angelo Bianchi Bonomi.
Recruitment status was: Active, not recruiting
First Posted : June 2, 2015
Results First Posted : April 19, 2016
Last Update Posted : May 19, 2016
|Condition or disease|
|Type 3 Von Willebrand's Disease|
Von Willebrand Disease (VWD) is the most common inherited bleeding disorder, characterized by a quantitative and/or qualitative deficiency of von Willebrand factor (VWF), that plays a major role in early phases of haemostasis. VWD type 3 (VWD3) is due to virtually complete deficiency of VWF and, for this reason, has been also described as "severe VWD". VWD3 is inherited as a recessive trait and heterozygous relatives have mild or no bleeding symptoms. Even if the prevalence of VWD3 is very low, the highest rate is found in Iran and the lowest in southern Europe. However, the actual prevalence of VWD3 is still unknown in most countries, due to the lack of retrospective or prospective studies. Although rare, VWD3 is of major interest because of its severe clinical presentation, the need for replacement therapy with VWF concentrates and the risk of occurrence of anti-VWF inhibitors after the infusion of VWF concentrates, for which risk factors have not been systematically determined.
The major objectives of the study are: to create an international network among European and Iranian Centers (ratio 1:1), the prospective enrollment of 250 VWD3 patients using a common database online, the collection of detailed information about previous bleedings and exposure to VWF concentrates, the use of bleeding severity score of VWD3 calculated with a common questionnaire, the evaluation of the presence of VWF gene defects with VWF phenotype and risk of anti-VWF inhibitors, the evaluation of anti-VWF antibody titre through common methods, the VWD3 gene analysis, the observation of frequency and sites of bleeding in VWD3 followed-up for 2 years, and the efficacy assessment of the VWF concentrates used to treat VWD3 using the most objective criteria for efficacy.
To these purposes, a cohort of 250 patients with diagnosis of Type 3 von Willebrand Disease will be enrolled using homogenous and standardized criteria.
The work planned to achieve the objectives of the project will be divided in three parts:
- the first part deals with standardized criteria for enrolment and collection of retrospective clinical and laboratory data, to be confirmed by centralized laboratories;
- the second part involves a further characterization of clinical and laboratory parameters, collected in the retrospective phase, including prevalence of anti-VWF inhibitors, advanced laboratory tests to further identify VWD3, mutations analyses of the VWF gene;
- the third part of the study for the first time deals with the prospective clinical observation in a large cohort of VWD3 patients all previously well characterized by an international panel of experts.
|Study Type :||Observational|
|Actual Enrollment :||266 participants|
|Official Title:||Type 3 Von Willebrand International Registries Inhibitor Prospective Study|
|Study Start Date :||December 2012|
|Estimated Primary Completion Date :||April 2018|
|Estimated Study Completion Date :||April 2018|
Type 3 VWD
Diagnosis of Type 3 von Willebrand Disease
- Bleeding Severity Score (BSS) [ Time Frame: 24 months (retrospective phase) ]The range of measurement is from -1 to +4 for each symptom considered (12 symptoms, total range from -12 to 48). For each symptom: 0=no symptom, 1=referred by the patient, 2=brought to medical attention, 3=major intervention. For spontaneous hemorrhagic symptoms, scores equal or greater than two require that the patient has specifically addressed that hemorrhagic symptom with a physician, whatever has been the diagnosis and therapy subsequently proposed. Score 0 and 1 are attributed to symptoms referred by the patient, hence without any precise medical intervention. Score 0 is for negligible or absent symptoms; 1 otherwise. For surgical procedures, it is considered important to differentiate between patients that have never bled because they never underwent surgery and those that did not bled after a surgery. These latter receive a negative score, indicating that the probability of VWD diminishes if you don't bleed after surgery.
- General Laboratory Tests for VWD3 Diagnosis (Composite) [ Time Frame: 36 months (retrospective + confirmatory phase) ]Hemoglobin: (mmol/L), HT(%), MVC (fl); Leucocytes: (E9/L); Neutrophil (%); Basophil (%); Eosinophil (%); Lymphocyte (%); Platelet count: (E9/L), MPV (fl); Prothrombin Time (sec); PTT (sec); PTT mix 50:50 (sec); Ferritin (ug/l); Bleeding Time (min:sec); Closure Time (Sec); Collagen/ADP (sec); Collagen/Epinephrine (sec); FVIII:C (IU/mL); VWF:RCo (IU/mL); VWF:Ag (IU/mL).
- Test for Anti-VWF Antibodies [ Time Frame: 36 months (retrospective + confirmatory phase) ]Evaluation of the titre of Anti-VWF Antibodies through Bethesda test (BU).
- Molecular Diagnosis of VWF in DNA [ Time Frame: 36 months (retrospective + confirmatory phase) ]Evaluation of the presence of VWF gene defects (confirmation or screening for the first time).
- Previous Use of Blood Products [ Time Frame: 24 months (retrospective) ]Record of any product used in the previous 24 months (collected type of blood products/VWF concentrate, year of first exposure, units used).
- Allergic Reactions During Use of VWF-containing Concentrates [ Time Frame: 24 months (retrospective) ]Record of any allergic and anaphilactic reactions occurred in the past due to the use of any VWF concentrate and the date of onset.
- Record of Bleeding Episodes [ Time Frame: 24 months (prospective phase) ]Bleeding: severity, start date, stop date; Treatment: Product name, start date, stop date, Total IU, Total ED.
- Adverse Events [ Time Frame: 24 months (prospective phase) ]Record of all adverse events occurred during the prospective phase of the study.
- Type of VWF/FVIII-containing Concentrates in Use [ Time Frame: 24 months (prospective phase) ]Record of any VWF/FVIII-containing concentrates used and currently in use, including the current schedule type of treatment.
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02460458
|Helsinki University Central Hospital, Department Internal Medicine, Coagulation Disorders, at Haematology and Laboratory Services|
|Helsinki, Finland, FIN-00029 HUS|
|Institut d'Hématologie - Hôpital Cardiologique - University of Lille - Haematology Department|
|Lille Cedex, France, 59037|
|Centre Régional de Traitement de l'Hémophilie - Laboratoire d'Hématologie|
|Nantes Cedex 1, France, 44093|
|University Clinic Bonn - Institute of Experimental Haematology & Transfusion Medicine|
|Bonn, Germany, 53127|
|University Children's Hospital - Department of Pediatric Hematology and Oncology|
|Hamburg, Germany, 20246|
|Department of Haematology, Haemostasis, Oncology and Stem Cell Transplantation - Hannover Medical School - Haemophilia Care Centre|
|Hannover, Germany, 30625|
|St. Istvan & St. Laszlo Hospital of Budapest - Hematology and Stem Cell Transplantation|
|Budapest, Hungary, 1097|
|Iran, Islamic Republic of|
|Ahvaz Jundishpur University of Medical Sciences - Research Center for Thalassemia & Hemoglobinopathy - Division of Hematology & Oncology|
|Ahwaz, Iran, Islamic Republic of|
|Seid-ol-Shohada Hospital - Hemophilia Center - Esfahan University of Medical Science|
|Esfahan, Iran, Islamic Republic of|
|Hemophilia- Thalassaemia Center of Mashhad (Sarvar Clinic) - Mashad University of Medical Science|
|Mashad, Iran, Islamic Republic of|
|Nemazee Hospital Hemophilia Center - Shiraz University of Medical Science|
|Shiraz, Iran, Islamic Republic of|
|Iranian Hemophilia Comprehensive Treatment Centre - Iranian Hemophilia Society|
|Tehran, Iran, Islamic Republic of|
|Mofid Comprehensive Care Centre for Children with Hemophilia - Shahid Beheshti University of Medical Science|
|Tehran, Iran, Islamic Republic of|
|Thrombosis Hemostasis Research Center - Vali-Asr Hospital - Emam Khmeini Complex Hospital - Tehran University of Medical Science|
|Tehran, Iran, Islamic Republic of|
|Azienda Ospedaliera Policlinico Consorziale di Bari - Unità Operativa Semplice di Emostasi e Trombosi|
|Bari, Italy, 70124|
|Azienda Ospedaliera Universitaria Careggi - Agenzia per l'Emofilia - Centro di Riferimento Coagulopatie Congenite|
|Firenze, Italy, 50141|
|Centro Emofilia e Trombosi - Fondazione Angelo Bianchi Bonomi - IRCCS Ospedale Ca' Granda - Dip. di Medicina Interna - Università degli Studi di Milano|
|Milano, Italy, 20122|
|Dipartimento di Biotecnologie Cellulari ed Ematologia - Università "Sapienza" di Roma - Policlinico Umberto I|
|Roma, Italy, 00161|
|Dipartimento di Terapie Cellulari ed Ematologia - Centro Malattie Emorragiche e Trombotiche - Ospedale San Bortolo|
|Vicenza, Italy, 36100|
|Leiden University Medical Center - Department of Hematology - Hemostasis and Thrombosis Center|
|Leiden, Netherlands, 2333|
|Erasmus Medical Center - Department of Hematology|
|Rotterdam, Netherlands, 3015|
|Complejo Hospitalario Universitario de A Coruña - Servicio de Hematología y Hemoterapia|
|A Coruña, Spain, 15006|
|Hospital Universitari General Vall d'Hebron - Unidad de Hemofilia|
|Barcelona, Spain, 08035|
|Hospital Universitario La Paz - Unidad de Hemofilia - Servicio de Hematología|
|Madrid, Spain, 28046|
|Lund University - Centre for Thrombosis and Haemostasis - Skane University Hospital|
|Malmö, Sweden, 205 02|
|Katherine Dormandy Haemophilia Centre and Thrombosis Unit - Royal Free Campus - University College London Medical School|
|London, United Kingdom, NW3 2PF|
|Central Manchester University Hospital NHS Foundation Trust - Manchester Royal Infirmary - Manchester Royal Eye Hospital|
|Manchester, United Kingdom, M13 9WL|
|Study Director:||Augusto B. Federici, MD||Hematology and Transfusion Medicine, L. Sacco University Hospital Department of Clinical & Community Sciences, University of Milan, Via Pace, 9 20122 Milan, Italy|
|Study Chair:||Pier M. Mannucci, MD||Scientific Direction IRCCS Maggiore Hospital Cà Granda Foundation, Via Francesco Sforza, 28, 20122 Milan, Italy|