Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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
Sponsor:
Collaborator:
Sintesi Research Srl
Information provided by (Responsible Party):
Fondazione Angelo Bianchi Bonomi

Brief Summary:
A 5 - year International Registries and Prospective Study on VWD Type 3, aimed to assess number, types and risk factors for bleeding and the efficacy and safety of VWF concentrates used to treat VWD patients .

Condition or disease
Type 3 Von Willebrand's Disease

Detailed Description:

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.

Layout table for study information
Study Type : Observational
Actual Enrollment : 266 participants
Observational Model: Cohort
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

Resource links provided by the National Library of Medicine


Group/Cohort
Type 3 VWD
Diagnosis of Type 3 von Willebrand Disease



Primary Outcome Measures :
  1. 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.

  2. 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).

  3. Test for Anti-VWF Antibodies [ Time Frame: 36 months (retrospective + confirmatory phase) ]
    Evaluation of the titre of Anti-VWF Antibodies through Bethesda test (BU).

  4. 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).

  5. 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).

  6. 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.

  7. 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.

  8. Adverse Events [ Time Frame: 24 months (prospective phase) ]
    Record of all adverse events occurred during the prospective phase of the study.

  9. 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
Venous blood sample, that will be used to obtain both citrated Platelet Poor Plasma for VWF assays and Cell Pellet for DNA extraction.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
A large cohort of patients with diagnosis of Type 3 von Willebrand Disease, enrolled in Europe and in Iran using homogeneous and standardized criteria.
Criteria

Inclusion Criteria:

  • Male and female of any age, including infants, children, adolescent and adults
  • Informed Consent obtained (parents should sign for patients < 18 y.o.)
  • Previous Diagnosis of VWD3 (VWF antigen: undetectable or <5 U/dL)
  • Detailed information on inherited pattern, history of bleeding, previous exposure to blood products
  • Availability of plasma and DNA samples

Exclusion Criteria:

• VWD3 patients who may not be available for follow-up


Information from the National Library of Medicine

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


Locations
Layout table for location information
Finland
Helsinki University Central Hospital, Department Internal Medicine, Coagulation Disorders, at Haematology and Laboratory Services
Helsinki, Finland, FIN-00029 HUS
France
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
Germany
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
Hungary
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
Italy
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
Netherlands
Leiden University Medical Center - Department of Hematology - Hemostasis and Thrombosis Center
Leiden, Netherlands, 2333
Erasmus Medical Center - Department of Hematology
Rotterdam, Netherlands, 3015
Spain
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
Sweden
Lund University - Centre for Thrombosis and Haemostasis - Skane University Hospital
Malmö, Sweden, 205 02
United Kingdom
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
Sponsors and Collaborators
Fondazione Angelo Bianchi Bonomi
Sintesi Research Srl
Investigators
Layout table for investigator information
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

Additional Information:
Publications:
von Willebrand EA. (1926) Hereditär Pseudohemofili. Finska Läkaresällskapets Handlingar 68, 87-112.
Federici AB, Bucciarelli P, Castaman G et al. (2007) Incidence and determinants of bleeding in different types of von Willebrand disease:results of the first prospective multicenter study on 814 Italian patients Blood 110, 713
Abuzenadah AM, Gursel T, Ingerslev J et al. (1999) Mutational analysis of the von Willebrand factor gene in 27 families from Turkey with von Willebrand disease Thromb Haemost 82 (Suppl), 283
Castaman G, Giacomelli SH, Coppola A et al. (2008) Molecular bases of type 3 von Willebrand disease in Italy: report on 12 families Blood Transfus Suppl 3, 44
Gazda H, Budde U, Krey S et al. (1997) Delta C in exon 18 of the von Willebrand factor gene is the most common mutation in patients with severe von Willebrand disease type 3 in Poland Blood 90 (Suppl 1), 94b
Titapiwatanakun R, Guenther JC, Asmann YW et al. (2007) Novel Mutations in Types 2 & 3 von Willebrand Disease and Correlation with von Willebrand Factor Multimer Patterns. Blood 110, 2136
Montgomery RR, Jozwiak MA, Hutter JJ et al. (1999) A homozygous variant of the von Willebrand factor (VWF) that fails to c-terminal dimerize resulting in loss of VWF multimers larger than dimer Blood 94 (Suppl 1), 443a
Schneppenheim R, Budde U, Drewke E et al. (1999) Cysteine mutations of von Willebrand factor correlate with different types of von Willebrand disease Thromb Haemost 82 (Suppl), 283
Enayat MS, Guilliatt AM, Surdhar GK et al. (2001) Identification of five novel mutations in families with type 3 von Willebrand's disease Thromb Haemost 86 (Suppl), P1810
Federici AB, Gianniello F, Canciani MT et al. (2005) Secondary long-term prophylaxis in severe patients with von Willebrand disease: an Italian cohort study Blood 106, 507a

Layout table for additonal information
Responsible Party: Fondazione Angelo Bianchi Bonomi
ClinicalTrials.gov Identifier: NCT02460458     History of Changes
Other Study ID Numbers: ABB-11-01
First Posted: June 2, 2015    Key Record Dates
Results First Posted: April 19, 2016
Last Update Posted: May 19, 2016
Last Verified: April 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Fondazione Angelo Bianchi Bonomi:
Factor VIII
Hemorrhage
von Willebrand Diseases
von Willebrand Factor
Additional relevant MeSH terms:
Layout table for MeSH terms
Von Willebrand Diseases
Von Willebrand Disease, Type 3
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Blood Platelet Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn