Survey of Inhibitors in Plasma-Product Exposed Toddlers
NCT ID: NCT01064284
Last Updated: 2017-08-25
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE4
303 participants
INTERVENTIONAL
2010-01-31
2015-05-31
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
BASIC_SCIENCE
NONE
Study Groups
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PLASMA DERIVED Factor VIII
Plasma-derived vWF/FVIII
PLASMA DERIVED Factor VIII
Maximum dosage : 50IU per kilo. 2-3 times per week or on demand during acute episode of bleeding
rFVIII
Recombinant FVIII
Recombinant FVIII
Maximum dosage : 50IU per kilo. 2-3 times per week or on demand during acute episode of bleeding
Interventions
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PLASMA DERIVED Factor VIII
Maximum dosage : 50IU per kilo. 2-3 times per week or on demand during acute episode of bleeding
Recombinant FVIII
Maximum dosage : 50IU per kilo. 2-3 times per week or on demand during acute episode of bleeding
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Any ethnicity
* Age \<6 years
* Severe haemophilia A (FVIII:C \<1%), as confirmed at enrolment by the central laboratory.
o Those patients diagnosed locally as severe but subsequently found to have FVIII levels \>= 1% on testing at the central laboratory will be separately recorded in the screening list.
* Previously untreated (0 EDs to any FVIII concentrates or blood products) or minimally treated (\<5 EDs) with blood components, namely whole blood, fresh frozen plasma, packed red blood cells, platelets or cryoprecipitate.
o Patients not meeting these criteria will be separately recorded in the screening list.
* Negative inhibitor measurement at both local and central laboratory at screening
* Ability to comply with study requirements
* Signed informed consent of legal tutors o Patients who will not accept to enter into the study or to be randomized will be separately recorded.
Exclusion Criteria
* Other congenital or acquired bleeding defects
* Plasma FVIII level \>= 1%, as assayed at the central laboratory
o Those patients originally diagnosed locally as severe but subsequently found to have FVIII levels ranging from 1% to 2% on testing at the central laboratory will be separately recorded in the screening list.
* Concomitant congenital or acquired immunodeficiency
* Concomitant treatment with systemic immunosuppressive drugs
* Concomitant treatment with any investigational drug
1 Minute
6 Years
MALE
No
Sponsors
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Sintesi Research Srl
INDUSTRY
Fondazione Angelo Bianchi Bonomi
OTHER
Responsible Party
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Principal Investigators
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Pier M. Mannucci, Professor
Role: PRINCIPAL_INVESTIGATOR
Fondazione Ca' Granda Ospedale Maggiore Policlinico Milano
Flora Peyvandi, Professor
Role: PRINCIPAL_INVESTIGATOR
Fondazione Ca' Granda Ospedale Maggiore Policlinico Milano
Locations
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City of Hope National Medical Center
Duarte, California, United States
Children's Hospital Los Angeles (CHLA)
Los Angeles, California, United States
Hemophilia and Thrombosis CenterUniversity of Colorado Denver - Anschutz Aurora
Aurora, Colorado, United States
Rush Hemophilia & Trombophilia Center - Rush University Medical Center
Chicago, Illinois, United States
Louisiana Center for Bleeding and Clotting Disorders, Tulane University Medical Center
New Orleans, Louisiana, United States
University of Mississippi Medical Center, Division of pediatric Hematology/Oncology
Jackson, Mississippi, United States
Children's Mercy Hospital
Kansas City, Missouri, United States
Hemophilia Treatment Center of Las Vegas
Las Vegas, Nevada, United States
MeritCare Roger Maris Cancer Center, Pediatric Oncology
Fargo, North Dakota, United States
Cook Children's Medical Center
Fort Worth, Texas, United States
Hospital de Ninos Sor Maria Ludovica La Plata Servicio de Hematologia
La Plata, Buenos Aires, Argentina
Fundacion de la Hemofilia
Buenos Aires, , Argentina
Landes- Frauen- und Kinderklinik Linz Abteilung für Kinder- und Jugendheilkunde
Linz, , Austria
Medizinische Universität Wien, Dept. Paediatrics
Vienna, , Austria
Centro de Pesquisa Clinica HEMORIO - Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti
Rio de Janeiro, , Brazil
Centro de Hematologia e Hemoterapia do e.s - Hemoes
Vitória, , Brazil
Hospital de Niños Dr. Luis Calvo Mackenna Centro Hemofílico
Santiago, , Chile
Centro de Hemofilicos del Hospital de Niños Roberto del Rio Instituto de Investigaciones Hematologicas
Santiago, , Chile
Paediatric Haematology department, Cairo University Pediatric Hospital
Cairo, , Egypt
Faculty of Medicine Ain Shams University Department Pediatrics
Cairo, , Egypt
Centre for Blood Disorders
Chennai, , India
St. John's Medical College & Hospital
Karnataka, , India
Kasturba Medical College, Manipal University
Karnataka, , India
Karnataka Hemophilia Care and Hematology Research Center
Karnataka, , India
Kerala Institute of Medical Science (KIMS)
Kerala, , India
Lokmanya TilakMunicipal Medical College &General Hospital - Sion
Mumbai, , India
All India Institute of Medical Sciences Department of Haematology
New Delhi, , India
Sir Ganga Ram Hospital
New Delhi, , India
Sahyadri Speciality Hospital
Pune, , India
Jehangir Clinical Development Centre, Department of Haematology, Jehangir Hospital Premises
Pune, , India
Hemophilia Center - Hematoogy & Oncology Dept. Shiraz University of Medical Science Ayatollah Dastgheib Hospital
Shiraz, , Iran
Comprehensive Care Center for Children with Hemophilia Mofid Children Hospital
Tehran, , Iran
Centro Emofilia e Trombosi "Angelo Bianchi Bonomi" Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano - Italy
Milan, , Italy
Clinica Medica II - Azienda Ospedaliera di Padova - Centro Emofilia di Padova
Padua, , Italy
Ematologia- UO Diagnostica Speciale e Terapia delle Malattie dell'Emostasi e della Trombosi- Università Sapienza - Policlinico Umberto I
Rome, , Italy
Unidad Medica de Alta Especialidad (UMAE), Hospital de Pediatria. Centro Medico Nacional de Occidente Istituto Mexicano del Seguro Social
Jalisco, , Mexico
Instituto Nacional de Pediatria
México D.F., , Mexico
Hospital Infantil de Mexico Federico Gomez
México, D.F., , Mexico
Hospital Universitario Dr. Josè Eleuterio Gonzalez de la UANL, NL. Mexico
Monterrey, , Mexico
Hospital de Especialidades UMAE Istituto Mexicano del Seguro Social (IMSS)
Monterrey (Nuevo Leòn), , Mexico
Kinf Faisal Specilist Hospital and Research Center
Riyadh, , Saudi Arabia
Haemophilia Comprehensive Care Clinic, Area 454, Charlotte Maxeke Johannesburg Academic Hospital
Parktown, , South Africa
Hospital Regional Universitario Carlos Haya
Málaga, , Spain
Hospital Universitario Virgen del Rocio Unidad de Hemofilia
Seville, , Spain
Hospital Universitario La Fe Unidad Coagulopatias Congenitas
Valencia, , Spain
Cukurova Universitesi, Tip Fakultesi Pediatrik Hematoloji B.D.
Adana, , Turkey (Türkiye)
Ege Üniversitesi Tip Fakültesi Cocuk Sağliği ve Hastalikari Anabilim Dali Pediatrik Hematoloji Bilim Dali
Bornova/Izmir, , Turkey (Türkiye)
Istanbul Üniversitesi Cerrahpaşa Tip Fakültesi Pediatrik Hematoloji B.D.
Istanbul, , Turkey (Türkiye)
Countries
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References
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Addiego J, Kasper C, Abildgaard C, Hilgartner M, Lusher J, Glader B, Aledort L. Frequency of inhibitor development in haemophiliacs treated with low-purity factor VIII. Lancet. 1993 Aug 21;342(8869):462-4. doi: 10.1016/0140-6736(93)91593-b.
Amano K, Arai M, Koshihara K, Suzuki T, Kagawa K, Nishida Y, Fukutake K. Autoantibody to factor VIII that has less reactivity to factor VIII/von Willebrand factor complex. Am J Hematol. 1995 Aug;49(4):310-7. doi: 10.1002/ajh.2830490409.
Auerswald G, Spranger T, Brackmann HH. The role of plasma-derived factor VIII/von Willebrand factor concentrates in the treatment of hemophilia A patients. Haematologica. 2003 Jun;88(6):EREP05.
Chalmers EA, Brown SA, Keeling D, Liesner R, Richards M, Stirling D, Thomas A, Vidler V, Williams MD, Young D; Paediatric Working Party of UKHCDO. Early factor VIII exposure and subsequent inhibitor development in children with severe haemophilia A. Haemophilia. 2007 Mar;13(2):149-55. doi: 10.1111/j.1365-2516.2006.01418.x.
Courter SG, Bedrosian CL. Clinical evaluation of B-domain deleted recombinant factor VIII in previously untreated patients. Semin Hematol. 2001 Apr;38(2 Suppl 4):52-9. doi: 10.1016/s0037-1963(01)90109-x.
Dasgupta S, Repesse Y, Bayry J, Navarrete AM, Wootla B, Delignat S, Irinopoulou T, Kamate C, Saint-Remy JM, Jacquemin M, Lenting PJ, Borel-Derlon A, Kaveri SV, Lacroix-Desmazes S. VWF protects FVIII from endocytosis by dendritic cells and subsequent presentation to immune effectors. Blood. 2007 Jan 15;109(2):610-2. doi: 10.1182/blood-2006-05-022756. Epub 2006 Sep 19.
Ehrenforth S, Kreuz W, Scharrer I, Linde R, Funk M, Gungor T, Krackhardt B, Kornhuber B. Incidence of development of factor VIII and factor IX inhibitors in haemophiliacs. Lancet. 1992 Mar 7;339(8793):594-8. doi: 10.1016/0140-6736(92)90874-3.
Goudemand J, Rothschild C, Demiguel V, Vinciguerrat C, Lambert T, Chambost H, Borel-Derlon A, Claeyssens S, Laurian Y, Calvez T; FVIII-LFB and Recombinant FVIII study groups. Influence of the type of factor VIII concentrate on the incidence of factor VIII inhibitors in previously untreated patients with severe hemophilia A. Blood. 2006 Jan 1;107(1):46-51. doi: 10.1182/blood-2005-04-1371. Epub 2005 Sep 15.
Gouw SC, van der Bom JG, Auerswald G, Ettinghausen CE, Tedgard U, van den Berg HM. Recombinant versus plasma-derived factor VIII products and the development of inhibitors in previously untreated patients with severe hemophilia A: the CANAL cohort study. Blood. 2007 Jun 1;109(11):4693-7. doi: 10.1182/blood-2006-11-056317. Epub 2007 Jan 11.
Gringeri A, Mantovani LG, Scalone L, Mannucci PM; COCIS Study Group. Cost of care and quality of life for patients with hemophilia complicated by inhibitors: the COCIS Study Group. Blood. 2003 Oct 1;102(7):2358-63. doi: 10.1182/blood-2003-03-0941. Epub 2003 Jun 19.
Gringeri A, Monzini M, Tagariello G, Scaraggi FA, Mannucci PM; Emoclot15 Study Members. Occurrence of inhibitors in previously untreated or minimally treated patients with haemophilia A after exposure to a plasma-derived solvent-detergent factor VIII concentrate. Haemophilia. 2006 Mar;12(2):128-32. doi: 10.1111/j.1365-2516.2006.01201.x.
Guerois C, Laurian Y, Rothschild C, Parquet-Gernez A, Duclos AM, Negrier C, Vicariot M, Fimbel B, Fressinaud E, Fiks-Sigaud M, et al. Incidence of factor VIII inhibitor development in severe hemophilia A patients treated only with one brand of highly purified plasma-derived concentrate. Thromb Haemost. 1995 Feb;73(2):215-8.
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Qadura M, Waters B, Burnett E, Chegeni R, Othman M, Lillicrap D. Investigating the mechanisms underlying FVIII antibody production in hemophilic mice following recombinant and plasma-derived FVIII infusion. Blood (ASH Annual Meeting Abstracts) 2008; 112: abstract #237.
Rothschild C, Laurian Y, Satre EP, Borel Derlon A, Chambost H, Moreau P, Goudemand J, Parquet A, Peynet J, Vicariot M, Beurrier P, Claeyssens S, Durin A, Faradji A, Fressinaud E, Gaillard S, Guerin V, Guerois C, Pernod G, Pouzol P, Schved JF, Gazengel C. French previously untreated patients with severe hemophilia A after exposure to recombinant factor VIII : incidence of inhibitor and evaluation of immune tolerance. Thromb Haemost. 1998 Nov;80(5):779-83.
Scharrer I, Ehrlich HJ. Reported inhibitor incidence in FVIII PUP studies: comparing apples with oranges? Haemophilia. 2004 Mar;10(2):197-8. doi: 10.1111/j.1365-2516.2004.00887.x. No abstract available.
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Rosendaal FR, Palla R, Garagiola I, Mannucci PM, Peyvandi F; SIPPET Study Group. Genetic risk stratification to reduce inhibitor development in the early treatment of hemophilia A: a SIPPET analysis. Blood. 2017 Oct 12;130(15):1757-1759. doi: 10.1182/blood-2017-06-791756. Epub 2017 Aug 2.
Peyvandi F, Mannucci PM, Garagiola I, El-Beshlawy A, Elalfy M, Ramanan V, Eshghi P, Hanagavadi S, Varadarajan R, Karimi M, Manglani MV, Ross C, Young G, Seth T, Apte S, Nayak DM, Santagostino E, Mancuso ME, Sandoval Gonzalez AC, Mahlangu JN, Bonanad Boix S, Cerqueira M, Ewing NP, Male C, Owaidah T, Soto Arellano V, Kobrinsky NL, Majumdar S, Perez Garrido R, Sachdeva A, Simpson M, Thomas M, Zanon E, Antmen B, Kavakli K, Manco-Johnson MJ, Martinez M, Marzouka E, Mazzucconi MG, Neme D, Palomo Bravo A, Paredes Aguilera R, Prezotti A, Schmitt K, Wicklund BM, Zulfikar B, Rosendaal FR. A Randomized Trial of Factor VIII and Neutralizing Antibodies in Hemophilia A. N Engl J Med. 2016 May 26;374(21):2054-64. doi: 10.1056/NEJMoa1516437.
Study Documents
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Document Type: Article
View DocumentRelated Links
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The official web site of the SIPPET Study
Other Identifiers
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2009-011186-88
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
ABB - 09 - 001
Identifier Type: -
Identifier Source: org_study_id
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