Reversal of vitamin K antagonist (VKA) induced anticoagulation in patients needing urgent surgery associated with significant bleeding risk. MedDRA version: 20.0 Level: PT Classification code 10065667 Term: Haemorrhage prophylaxis System Organ Class: 10042613 - Surgical and medical procedures
Conditions
Interventions
Trade Name: Octaplex
Product Name: Octaplex
Pharmaceutical Form: Powder and solvent for concentrate for solution for infusion
INN or Proposed INN: PROTHROMBIN COMPLEX CONCENTRATE
CAS Number: 37224-63-
Sponsors
Octapharma Pharmazeutika Produktionsges.m.b.H
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients at least 18 years of age. 2. Patients currently on oral anticoagulation treatment with VKA of coumadin or warfarin type. 3. Patients being admitted to the hospital or currently hospitalized where: • an urgent surgery carrying significant bleeding risk (=50 mL expected blood loss in normal coagulation state) is required as part of routine clinical care within 24 hours of the start of the investigational medicinal product; • VKA withdrawal and use of oral or parenteral vitamin K alone to reverse anticoagulation is deemed too slow or inappropriate for reversal; 4. Patients with an INR of 2.0 or above at the time of decision to reverse the anticoagulation status. 5. Patients who have given written informed consent and who are able and willing to comply with the procedures laid out in the study protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 222 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 148
Exclusion criteria
Exclusion criteria: 1. Patients with a life expectancy of less than 48 hours per physician’s judgment (e.g., patients with a Glasgow Coma Scale equal to 3 or a head Abbreviated Injury Score of 6, patients requiring continuous inotropic or pressor support, and patients whose status is post cardiac arrest). 2. Patients for whom the planned surgery or procedure is commonly associated with a very low bleeding risk (e.g., catheter placement, gastroscopy). 3. Patients with a history of TEEs, myocardial infarction (MI), unstable angina pectoris, critical aortic stenosis, cerebrovascular accident, TIA, severe peripheral vascular disease (e.g. Fontaine IV), or disseminated intravascular coagulation within 3 months of enrollment. (Note: ongoing thrombosis in-situ or severe unilateral peripheral arterial disease (PAD) undergoing surgical intervention is not an exclusion criterion). 4. Patients with a known congenital bleeding disorder. 5. Patients with a known antiphospholipid antibody syndrome. 6. Patients with present or past specific factor inhibitor activity. 7. Patients with thrombocytopenia of <80,000/µL or history of heparin-induced thrombocytopenia. 8. Patients who have received more than 5000 units of systemic unfractionated heparin (UFH), any dose of low-molecular-weight heparin (LMWH) or any dose of non-VKA anticoagulant (i.e. direct oral anticoagulant) within 24 hours prior to enrollment into the study or have potential need to receive these medications in mentioned doses before completion of hemostasis evaluation at the end of surgery. 9. Patients who have received PCCs, FFP or vitamin K within 72 hours prior to enrollment into the study. 10. Patients receiving P2Y12 platelet inhibitors (e.g. Clopidogrel, Prasugrel, Ticagrelor) 11. Patients with a known history of hypersensitivity to plasma-derived products. 12. Patients requiring urgent surgical procedures where according to the surgeon's clinical judgment an accurate estimate of expected blood loss and transfusion requirements is not possible, e.g.: a. Surgeries requiring massive transfusion protocols (e.g., major polytrauma, major injuries, organ transplant surgeries), b. Patients with acute major bleeding (e.g. gastrointestinal bleeds, obstetric haemorrhage), c. Surgeries with unpredictable intraoperative blood loss (e.g., ruptured aneurysm, primary surgery for intracranial hemorrhage (ICH)). 13. Pregnant or nursing women. 14. Patients participating in another interventional clinical study currently or during the past 30 day prior to enrollment into this study. 15. Patients previously enrolled in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to demonstrate that the efficacy of OCTAPLEX as a reversal agent in patients under VKA therapy with the need for urgent surgery with significant bleeding risk is clinically non-inferior to Beriplex® P/N (Kcentra).;Secondary Objective: The secondary objective of the study is to investigate the safety and tolerability of OCTAPLEX compared to Beriplex® P/N (Kcentra) in patients under VKA therapy with the need for urgent surgery with significant bleeding risk.;Primary end point(s): The primary efficacy endpoint is the hemostatic efficacy rating at the end of the surgery.;Timepoint(s) of evaluation of this end point: End of surgery. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Proportion of patients with an INR value of less than or equal to 1.5 at 30 min (± 15 min) after the end of infusion. • Change in coagulation factor levels from baseline to 30 (± 15 min) after the end of infusion: o Factor FII o Factor FVII o Factor FIX o Factor FX • Proportion of patients receiving red blood cells (RBC) during the surgery ;Timepoint(s) of evaluation of this end point: • Proportion of patients with an INR value of less than or equal to 1.5 at 30 min (± 15 min) after the end of infusion. • Change in coagulation factor levels from baseline to 30 (± 15 min) after the end of infusion: o Factor FII o Factor FVII o Factor FIX o Factor FX • Proportion of patients receiving red blood cells (RBC) during the surgery | — |
Countries
Bulgaria, Germany, Poland, Romania, Russian Federation, Spain, Ukraine, United States
Contacts
Public ContactClinical Research & Development
Octapharma Pharmazeutika Produktionsges.m.b.H
Outcome results
None listed