Účinnost Atenativu u pacientů s vrozeným nedostatkem antitrombinu podstupujících operaci nebo porod
Multicentrická, prospektivní, otevřená, nekontrolovaná studie fáze 3 k posouzení účinnosti, bezpečnosti a farmakokinetiky přípravku Atenativ u pacientů s vrozeným nedostatkem antitrombinu, kteří podstupují operaci nebo porod
The goal of this study is to assess the incidence of the composite of thrombotic events (TEs) and thromboembolic events (TEEs) in patients with congenital antithrombin deficiency under when they receive Atenativ for surgical procedures or parturition.
Přehled studie
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 3
Kontakty a umístění
Studijní kontakt
- Jméno: Sigurd Knaub
- Telefonní číslo: +41554512141
- E-mail: Sigurd.Knaub@octapharma.com
Studijní místa
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Yerevan, Arménie
- Nábor
- Yeolyan Hematology and Oncology Centre
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Bron, Francie
- Nábor
- Centre de Référence de l'Hémophilie Unité d'Hémostase Clinique Hôpital Cardiologique Louis Pradel
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Reims, Francie
- Nábor
- University Hospital of Reims
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Rouen, Francie
- Nábor
- Centre Hospitalier Universitaire de Rouen (CHU de Rouen) - Centre de Traitement des Maladies Hemorragiques (CRTH) (Centre d'Hemophiles)
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Tbilisi, Gruzie
- Nábor
- Aversi Clinic
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Bergamo, Itálie, 24127
- Nábor
- Unita Strutturale Complessa di Immunoematologia e Medicina Trasfusionale -Dipartimento Interaziendale di Medicina Trasfusionale ed Ematologia - ASST Papa Giovanni XXIII ematologia Piazza OMS, 1
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Milan, Itálie
- Nábor
- Universita degli Studi di Milano - IRCCS Ospedale Maggiore Policlinico - Centro Emofilia e Trombosi Angelo Bianchi Bonomi
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Padua, Itálie
- Nábor
- University of Padua Medical School
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Roma, Itálie
- Nábor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
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Petah Tikva, Izrael
- Nábor
- Rabin Medical Centre, Institute of Haematology
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Ramat Gan, Izrael
- Nábor
- Sheba Medical Centre
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Debrecen, Maďarsko
- Nábor
- University of Debrecen, Medical and Health Science Centre
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Berlin, Německo
- Nábor
- Vivantes Klinikum Friedrichshain Klinik für Angiologie Hämostaseologie
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Bonn, Německo
- Nábor
- UKB Bonn Institut für Experimentelle Hämatologie und Transfusionsmedizin
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Duisburg, Německo
- Nábor
- Gerinnungszentrum Rhein-Ruhr
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Vienna, Rakousko
- Nábor
- Medizinische Universität Wien. Universitätsklinik für Innere Medizin Klinische Abteilung für Hämatologie und Hämostaseologie
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Craiova, Rumunsko
- Nábor
- Emergency County Hospital Craiova
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London, Spojené království
- Nábor
- Royal-free Hospital-Katherine Dormandy Haemophilia and Thrombosis Centre
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London, Spojené království
- Nábor
- St. Thomas Hospital, Guy's and St. Thomas' NHS Foundation Trust
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District of Columbia
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Washington D.C., District of Columbia, Spojené státy, 20057
- Nábor
- Georgetown University Hospital
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Florida
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Miami, Florida, Spojené státy, 33124
- Nábor
- University of Miami, Miller School of Medicine
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Illinois
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Peoria, Illinois, Spojené státy, 61615
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- Bleeding and Clotting Disorders Institute
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New York
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New York, New York, Spojené státy, 10065
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- Weill Cornell Medicine, New York Presbyterian Hospital
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North Carolina
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Durham, North Carolina, Spojené státy, 27708
- Nábor
- Duke University School of Medicine, Division of Hematology
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Belgrade, Srbsko
- Nábor
- Clinical Center of Serbia
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Nymburk, Česko
- Nábor
- Centre for Thrombosis and Haemaostasis Nemocnice
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Madrid, Španělsko, 28046
- Nábor
- Hospital Universitario La Paz
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Murcia, Španělsko
- Nábor
- Hospital Universitario Morales Meseguer
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Ourense, Španělsko, 32005
- Nábor
- Ourense University Hospital
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Principality of Asturias
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Oviedo, Principality of Asturias, Španělsko, 33011
- Nábor
- Central University Hospital of Asturias
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- Adult male or female patients ≥18 and ≤80 years of age. Solely in the US, 4 male or female patients between ≥12 and <17 years of age will be enrolled into the PK phase, and subsequently in the treatment phase, if applicable
- Documented congenital antithrombin deficiency, defined by plasma activity level of antithrombin ≤60% from medical history
- Personal or family history of TEs or TEEs (except for PK patients)
- For the Treatment Phase: either a) non-pregnant surgical patients scheduled for elective surgical procedure(s) known to be associated with a high risk for occurrence of TEs or TEEs, or b) pregnant patients of at least 27 weeks gestational age who are scheduled for caesarean section or delivery
- For female patients of childbearing potential entering the PK Phase who are not known to be pregnant, and for female surgical patients of childbearing potential entering the Treatment Phase for any procedure other than caesarean section or delivery, a negative urine pregnancy test at screening and at baseline
- Patient has provided informed consent
Exclusion Criteria:
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Requires emergency surgery or emergency caesarean section
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Has undergone surgery within the last 6 weeks
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History or suspicion of another hereditary thrombophilic disorder other than antithrombin deficiency (e.g., activated protein C [APC] resistance/Factor V Leiden, Protein S or C deficiency, prothrombin gene mutation [G20210A], or acquired [lupus anticoagulant] thrombophilic disorder)
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Malignancies, renal failure (patients on renal replacement therapy), or severe liver disease (aspartate aminotransferase [ASAT] >5 times the upper limit of normal)
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Body mass index >40 kg/m2 (for non-pregnant patients, only)
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Known hypersensitivity or allergic reaction to antithrombin or any of the excipients in Atenativ
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History of anaphylactic reaction(s) to blood or blood components
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Refusal to receive transfusion of blood-derived products
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Administration of any antithrombin concentrate or antithrombin-containing blood product within 14 days of either of the two phases of the study
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Prior diagnosis of heparin-induced thrombocytopenia
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TE or TEE within the last 6 months
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Female patients who are nursing at the time of screening*
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Have participated in another investigational study within the last 30 days
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Persons dependent on the sponsor, the investigator or the centre of investigation
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Persons placed in an institution by administrative or judicial order
- criterion does not include female patients who plan to breastfeed after giving birth
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Prevence
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Experimentální: Atenativ treatment
During the PK phase, patients will receive a 60 IU/kg Atenativ as a single intravenous infusion for PK analysis. During the treatment phase, patients will receive a single intravenous loading dose followed by maintenance doses administered every 24 hours for approximately 2-7 days for surgical patients and approximately 5 days for parturients |
Antithrombin concentrate |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Thrombotic event incidence
Časové okno: Up to day 30 post treatment initiation
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The primary objective of this study is to assess the incidence of the composite of TEs and TEEs in patients with congenital antithrombin deficiency under cover of Atenativ for surgical procedures or parturition |
Up to day 30 post treatment initiation
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Single dose Pharmacokinetics of Atenativ: Area under the curve (AUCnorm(0-∞))
Časové okno: Up to day 14 post PK infusion
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Assess the area under the curve (AUCnorm(0-∞)) of Atenativ in patients with congenital antithrombin deficiency |
Up to day 14 post PK infusion
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Single dose Pharmacokinetics of Atenativ: Maximum plasma concentration (Cmax)
Časové okno: Before first infusion, 20 minutes, 1 hour, 3 hours, 8 hrs, 1 day, 2 days, 3, days, 4 days, 5 days, 6 days, 7 days, 8 days, 10 days, 12 days and 14 days post-infusion
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Assess the maximum plasma concentration (Cmax) after a single dose of Atenativ in patients with congenital antithrombin deficiency |
Before first infusion, 20 minutes, 1 hour, 3 hours, 8 hrs, 1 day, 2 days, 3, days, 4 days, 5 days, 6 days, 7 days, 8 days, 10 days, 12 days and 14 days post-infusion
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Single dose Pharmacokinetics of Atenativ: Half-life (t1/2)
Časové okno: Before first infusion, 20 minutes, 1 hour, 3 hours, 8 hrs, 1 day, 2 days, 3, days, 4 days, 5 days, 6 days, 7 days, 8 days, 10 days, 12 days and 14 days post-infusion
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Assess the half-life (t1/2) after a single dose of Atenativ in patients with congenital antithrombin deficiency |
Before first infusion, 20 minutes, 1 hour, 3 hours, 8 hrs, 1 day, 2 days, 3, days, 4 days, 5 days, 6 days, 7 days, 8 days, 10 days, 12 days and 14 days post-infusion
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Single dose Pharmacokinetics of Atenativ: Mean residence time (MRT)
Časové okno: Before first infusion, 20 minutes, 1 hour, 3 hours, 8 hrs, 1 day, 2 days, 3, days, 4 days, 5 days, 6 days, 7 days, 8 days, 10 days, 12 days and 14 days post-infusion
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Assess the mean residence time (MRT) after a single dose of Atenativ in patients with congenital antithrombin deficiency |
Before first infusion, 20 minutes, 1 hour, 3 hours, 8 hrs, 1 day, 2 days, 3, days, 4 days, 5 days, 6 days, 7 days, 8 days, 10 days, 12 days and 14 days post-infusion
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Single dose Pharmacokinetics of Atenativ: Clearance (CL)
Časové okno: Before first infusion, 20 minutes, 1 hour, 3 hours, 8 hrs, 1 day, 2 days, 3, days, 4 days, 5 days, 6 days, 7 days, 8 days, 10 days, 12 days and 14 days post-infusion
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Assess the clearance (CL) after a single dose of Atenativ in patients with congenital antithrombin deficiency |
Before first infusion, 20 minutes, 1 hour, 3 hours, 8 hrs, 1 day, 2 days, 3, days, 4 days, 5 days, 6 days, 7 days, 8 days, 10 days, 12 days and 14 days post-infusion
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Single dose Pharmacokinetics of Atenativ: Incremental in vivo recovery (IVR)
Časové okno: Before first infusion, 20 minutes, 1 hour, 3 hours, 8 hrs, 1 day, 2 days, 3, days, 4 days, 5 days, 6 days, 7 days, 8 days, 10 days, 12 days and 14 days post-infusion
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Assess the Incremental in vivo recovery after a single dose of Atenativ in patients with congenital antithrombin deficiency |
Before first infusion, 20 minutes, 1 hour, 3 hours, 8 hrs, 1 day, 2 days, 3, days, 4 days, 5 days, 6 days, 7 days, 8 days, 10 days, 12 days and 14 days post-infusion
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Single dose Pharmacokinetics of Atenativ: Volume of distribution at steady state (Vss)
Časové okno: Before first infusion, 20 minutes, 1 hour, 3 hours, 8 hrs, 1 day, 2 days, 3, days, 4 days, 5 days, 6 days, 7 days, 8 days, 10 days, 12 days and 14 days post-infusion
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Assess the volume of distribution at steady state (Vss) after a single dose of Atenativ in patients with congenital antithrombin deficiency |
Before first infusion, 20 minutes, 1 hour, 3 hours, 8 hrs, 1 day, 2 days, 3, days, 4 days, 5 days, 6 days, 7 days, 8 days, 10 days, 12 days and 14 days post-infusion
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Single dose Pharmacokinetics of Atenativ: Maximum Plasma Concentration (Tmax)
Časové okno: Before first infusion, 20 minutes, 1 hour, 3 hours, 8 hrs, 1 day, 2 days, 3, days, 4 days, 5 days, 6 days, 7 days, 8 days, 10 days, 12 days and 14 days post-infusion
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Assess the time to reach Maximum Plasma Concentration (Tmax) after a single dose of Atenativ in patients with congenital antithrombin deficiency |
Before first infusion, 20 minutes, 1 hour, 3 hours, 8 hrs, 1 day, 2 days, 3, days, 4 days, 5 days, 6 days, 7 days, 8 days, 10 days, 12 days and 14 days post-infusion
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10. Coagulation parameters: Activated partial thromboplastin time [aPTT]
Časové okno: Up to day 7 post treatment initiation
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Assess activated partial thromboplastin time [aPTT] in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition |
Up to day 7 post treatment initiation
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Coagulation parameters: Prothrombin time [PT]
Časové okno: Up to day 7 post treatment initiation
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Assess prothrombin time [PT] in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition |
Up to day 7 post treatment initiation
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Coagulation parameters: International normalised ratio [INR]
Časové okno: Up to day 7 post treatment initiation
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Assess international normalised ratio [INR] in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition |
Up to day 7 post treatment initiation
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Coagulation parameters: Fibrinogen level
Časové okno: Up to day 7 post treatment initiation
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Assess fibrinogen in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition |
Up to day 7 post treatment initiation
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Safety and tolerability: Number of adverse events (AEs)
Časové okno: Up to day 30 post treatment initiation
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Number of adverse events (AEs) following treatment with Atenativ in patients with congenital antithrombin deficiency |
Up to day 30 post treatment initiation
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Spolupracovníci a vyšetřovatelé
Sponzor
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
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