Phase 3 Study on the Efficacy and Safety of Human Plasma Derived Antithrombin (Atenativ) in Heparin-Resistant Patients Scheduled to Undergo Cardiac Surgery Necessitating Cardiopulmonary Bypass

Официальное название

Phase 3, Double-blind, Placebo-controlled, Multicentre Study on the Efficacy and Safety of Human Plasma Derived Antithrombin (Atenativ) in Heparin-Resistant Patients Scheduled to Undergo Cardiac Surgery Necessitating Cardiopulmonary Bypass

Обзор

The primary objective of this study is to evaluate the efficacy of two different doses of Atenativ, versus placebo, in restoring and maintaining heparin responsiveness in adult patients undergoing cardiac surgery necessitating cardiopulmonary bypass (CPB)

Вмешательства

• Препарат Human plasma derived antithrombin
  A solvent/detergent and heat-treated antithrombin concentrate derived from human plasma
• Препарат Placebo
  Half of the patients in the placebo group will be randomised to receive a volume of placebo corresponding to the low dose of Atenativ and the other half to receive a volume of placebo corresponding to a high dose of Atenativ

Первичные конечные точки

• Restoring heparin responsiveness [Срок оценки: During surgery (from the time of the first surgical incision to the time at which the final suture or staple is placed)]

Вторичные конечные точки (12)

• Amounts of further therapy for restoring heparin responsiveness [Срок оценки: During surgery (from the time of the first surgical incision to the time at which the final suture or staple is placed)]
• Change in activated clotting time (ACT) values [Срок оценки: Within 5 minutes following intravenous administration of 500 U/kg unfractionated heparin (UFH) and between 2-10 minutes after IMP infusion]
• Change in antithrombin plasma levels [Срок оценки: Within 10 minutes before IMP infusion and between 2 and 10 minutes after IMP infusion, within 10 minutes after the end of CPB, at the end of surgery, and at 24 hours after the start of IMP infusion]
• Change in heparin usage [Срок оценки: From end of IMP infusion to the end of surgery]
• FP unit use [Срок оценки: From the start of IMP infusion until 24 hours following IMP infusion, and until discharge or 7 days after surgery, whichever comes first]
• Amounts of further antithrombin concentrate for maintaining heparin responsiveness [Срок оценки: From placement of the final suture or staple until 24 hours following IMP infusion, to discharge or 7 days after surgery, whichever comes first]
• Transfusion of allogenic blood products [Срок оценки: From the start of IMP infusion until 24 hours after the start of Atenativ or placebo infusion and until discharge or 7 days after surgery, whichever comes first]
• Administration of coagulation factor concentrates [Срок оценки: From the start of IMP infusion until 24 hours after the start of Atenativ or placebo infusion and until discharge or 7 days after surgery, whichever comes first]
• Administration of other haemostatic-relevant therapies [Срок оценки: From the start of IMP infusion until 24 hours after the start of Atenativ or placebo infusion and until discharge or 7 days after surgery, whichever comes first]
• Postoperative chest tube drainage [Срок оценки: From the start of IMP infusion to 24 hours after infusion and until discharge or 7 days after surgery, whichever comes first]
• Need for reoperation due to bleeding [Срок оценки: 24 hours after the start of IMP infusion]
• Cell saver volume [Срок оценки: During surgery (from the time of the first surgical incision to the time at which the final suture or staple is placed)]

Критерии участия

Критерии включения

• Planned cardiac surgery with CPB
• Heparin-resistant patients (pre-CPB Hemochron ACT less than 480 s in the measurement taken between 2-5 minutes following intravenous administration of 500 U/kg UFH)
• Patients between 18 and 85 years of age, inclusive
• Freely given written or electronic informed consent
• In female patients of childbearing potential, a pre-existing negative pregnancy test within 14 days prior to surgery

Критерии исключения

• Receiving, or have received within the timeframes specified, one or more of the following medications prior to the start of surgery:

• vitamin K antagonists (within 3 days)
• direct oral anticoagulants (within 2 days)
• thienopyridines (ticlopidine within 14 days, prasugrel within 7 days, or clopidogrel within 5 days), unless platelet function is satisfactory according to local standard of care assessment
• ticagrelor (within 5 days), unless platelet function is satisfactory according to local standard of care assessment
• glycoprotein IIb/IIIa antagonist (within 24 hours)
• Pre-existing coagulopathy, a history of bleeding problems, or a laboratory-diagnosed bleeding disorder (e.g., von Willebrand disease, platelet disorder)
• Renal insufficiency, defined as serum creatinine level >2.0 mg/dL
• Thrombocytosis, defined as platelet count >400,000 per μL
• Known hypersensitivity or allergic reaction to antithrombin or any of the excipients in Atenativ, i.e., human albumin, sodium chloride, acetyl tryptophan, caprylic acid
• History of anaphylactic reaction(s) to blood or blood components
• Refusal to receive transfusion of blood or blood-derived products
• Current participation in another interventional clinical trial or previous participation in the current trial
• Treatment with any IMP within 30 days prior to screening visit

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 9 центров

• Stanford University School of Medicine — Stanford
• University of Miami — Miami
• Massachusetts General Hospital — Boston
• Duke University Medical Center — Durham
• Atrium Health Wake Forest Baptist — Winston-Salem
• Cleveland Clinic — Cleveland
• The Ohio State University — Columbus
• OU Health University of Oklahoma Medical Center — Oklahoma City
• … и ещё 1 центр

Канада · 4 центра

• Royal Columbian Hospital — New Westminster
• Kingston Health Sciences Centre — Kingston
• Toronto General Hospital — Toronto
• Montreal Heart Institute — Montreal

Великобритания · 3 центра

• Royal Papworth Hospital — Cambridge
• University Hospital Coventry and Warwickshire — Coventry
• The James Cook University Hospital — Middlesbrough

Австрия · 2 центра

• University Hospital Innsbruck — Innsbruck
• Vienna General Hospital AKH, Medical University of Vienna — Vienna

Чехия · 2 центра

• Center of Cardiovascular and Transplant Surgery — Brno
• Institute for Clinical and Experimental Medicine — Prague

Франция · 2 центра

• CHU de Reims, Hôpital Robert Debré — Reims
• CHU de Rennes — Rennes

Литва · 2 центра

• Hospital of Lithuanian university of Health sciences Kauno Klinikos — Kaunas
• Vilnius University hospital Santaros Klinikos — Vilnius

Румыния · 1 центр

• Institute for Cardiovascular Diseases C.C. Iliescu — Bucharest

Сербия · 1 центр

• Institute of Cardiovascular Diseases Vojvodina — Kamenitz

Словения · 1 центр

• University Medical Centre Ljubljana — Ljubljana

Идентификаторы

NCT: NCT06096116 · ATN-108

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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