Efficacy and Safety of 4F-PCC (4-Factor Prothrombin Complex Concentrate) in Adult Patients Undergoing Complex Cardiovascular Surgery With Cardiopulmonary Bypass (CPB)

Официальное название

A Phase 3, Multicenter, Randomized, Open-label, Controlled Study to Investigate the Efficacy and Safety of 4-Factor Prothrombin Complex Concentrate in Adult Patients Undergoing Complex Cardiovascular Surgery With Cardiopulmonary Bypass

Обзор

This is a phase 3, multicenter, randomized, open-label, parallel-group, controlled study to assess the efficacy and safety of BE1116 compared with fresh frozen plasma (FFP) in adult participants undergoing complex cardiovascular surgery with CPB. The primary purpose of the study is to compare the efficacy of BE1116 and FFP in correcting coagulation factor deficiencies in bleeding participants undergoing complex cardiovascular surgery with CPB.

Вмешательства

• Биопрепарат BE1116
  A single dose of BE1116 will be administered by intravenous (IV) infusion intraoperatively.
• Биопрепарат FFP
  A single dose of FFP will be administered as investigational product (IP) by IV infusion intraoperatively.

Первичные конечные точки

• Number of Participants With and Without a Successful Correction of Coagulation Factor Deficiency [Срок оценки: At Day 1 after IP infusion (30 minutes after the end of infusion)]

Вторичные конечные точки (12)

• Number of Participants With Effective or Not Effective Hemostatic Response from 30 Minutes to 24 Hours After the End of IP Infusion [Срок оценки: Up to 24 hours after the end of IP infusion]
• Number of Participants With and Without Successful Correction of Coagulation Factor Deficiency [Срок оценки: At Day 1 after IP infusion (30 minutes after the end of infusion)]
• Change in INR from Baseline [Срок оценки: From baseline (before IP infusion), to 30 minutes, 6 hours, 24 hours, and 48 hours after the end IP infusion]
• Number of Participants With Effective and Not Effective Hemostatic Response From the Start of IP Infusion to 24 Hours After the Start of IP Infusion [Срок оценки: Up to 24 hours after the start of IP infusion]
• Change in Z-Scores for ROTEM EXTEM CT and TEG Reaction Time [Срок оценки: From baseline (before IP infusion) to 30 minutes and 24 hours after the end IP infusion]
• Change in Bleeding Severity Scale (BSS) Score From Baseline [Срок оценки: From baseline (before IP infusion) to 30 minutes after end of IP infusion]
• Number of Participants in Each Universal Definition for Perioperative Bleeding (UDPB) Class [Срок оценки: During surgery (Day 1) and on the first postoperative day (Day 2)]
• Total Number of Units of Allogeneic Blood Products (ABPs) Administered [Срок оценки: From the start of IP infusion and up to 24 hours and 5 days after surgery]
• Number of Units of Individual ABPs Administered [Срок оценки: Up to 24 hours after the start of IP infusion]
• Volume of Chest Tube Output [Срок оценки: Up to 24 hours after the end of surgery]
• Number of Participants Requiring Reoperation for Bleeding and for Other Reasons [Срок оценки: Up to 30 days after surgery]
• Duration of Mechanical Ventilation [Срок оценки: Up to 30 days after surgery]

Критерии участия

Критерии включения

• Adult greater than or equal to (≥) 18 years and has provided written informed consent.
• Undergoing elective complex cardiovascular surgery requiring CPB, including procedures of the thoracic aorta (with or without additional cardiac interventions), aortic valve replacement + coronary artery bypass graft (CABG), complex valve surgeries, mitral valve repair + CABG, and mitral valve replacement + CABG and reoperative CABG. Reoperative procedures are permitted. Excluded surgeries are as follows: heart transplantation, insertion or removal of ventricular assist devices (except for intra-aortic balloon pumps), and acute repair of thoracoabdominal aneurysms.
• Coagulation factor replacement (ie, 4F-PCC or FFP) is ordered in the operating room for the management of bleeding, in accordance with accepted clinical standards. The following criteria must be met:
• INR ≥ 1.6 (point-of-care INR testing by Hemochron ≥ 5 to 10 minutes after protamine infusion for heparin reversal). If a participant needs a second dose of protamine, a new INR measurement should be performed to confirm eligibility.
• Significant microvascular hemorrhage (ie, not due to surgical complications), as defined by a BSS score of ≥ 2.

Критерии исключения

• Administration of any systemic hemostatic therapy, such as cryoprecipitate, platelets, FFP, PCC (eg, 4-factor / 3-factor PCC \[4F-PCC / 3F-PCC\]), Factor VIII (FVIII) inhibitor bypassing activity (FEIBA), recombinant activated Factor VIIa (rFVIIa), or other coagulation factor products, in the 24 hours before study surgery, except when FFP is added to the CPB circuit.

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

Открытое

Основная цель

Лечение

Центры проведения

США · 10 центров

• UCLA Health - Ronald Reagan Medical Center — Los Angeles
• University of Chicago Medicine — Chicago
• University of Maryland Medical Center (UMMC) — Baltimore
• North Shore University Hospital — Manhasset
• University of Cincinnati — Cincinnati
• OUHSC (University of Oklahoma Health Sciences Center) — Oklahoma City
• Oregon Health & Sciences University — Portland
• Thomas Jefferson University Hospital — Philadelphia
• … и ещё 2 центра

Канада · 4 центра

• Kingston Health Science Center — Kingston
• London Health Sciences Center - University Campus — London
• University of Toronto - St. Michael's Hospital (SMH) - Keenan Research Centre for Biomedic — Toronto
• Universite de Montreal-Institut de Cardiologie de Montreal (ICM) Montreal Heart Institute — Montreal

Япония · 3 центра

• Kyushu University Hospital — Fukuoka
• National Cerebral and Cardiovascular Center — Suita
• Sakakibara Heart Institute — Fuchu-shi

Мексика · 1 центр

• Hospital Civil de Guadalajara — Guadalajara

Идентификаторы

NCT: NCT07094087 · BE1116_3008

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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