A Phase III, randomized, double-blind, multicenter study to assess the efficacy and safety of OCTAPLEX, a four-factor prothrombin complex concentrate (4F-PCC), compared to the 4F-PCC Beriplex® P/N (Kcentra), for the reversal of vitamin K antagonist induced anticoagulation in patients needing urgent surgery with significant bleeding risk.

• Register: EUCTR
• Last refreshed on: 20 August 2018
• Main ID: EUCTR2016-002649-41-ES
• Date of registration: 06/03/2017
• Prospective Registration: Yes
• Primary sponsor: Octapharma Pharmazeutika Produktionsges.m.b.H
• Public title: A Phase III, randomized, double-blind, multicenter study to assess the efficacy and safety of OCTAPLEX, a four-factor prothrombin complex concentrate (4F-PCC), compared to the 4F-PCC Beriplex® P/N (Kcentra), for the reversal of vitamin K antagonist induced anticoagulation in patients needing urgent surgery with significant bleeding risk.
• Scientific title: A Phase III, randomized, double-blind, multicenter study to assess the efficacy and safety of OCTAPLEX, a four-factor prothrombin complex concentrate (4F-PCC), compared to the 4F-PCC Beriplex® P/N (Kcentra), for the reversal of vitamin K antagonist induced anticoagulation in patients needing urgent surgery with significant bleeding risk.
• Date of first enrolment: 08/03/2017
• Target sample size: 370
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002649-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Germany, Poland, Romania, Russian Federation, Spain, Ukraine, United States

Contacts

• Name: Clinical Research & Development
• Affiliation: Octapharma Pharmazeutika Produktionsges.m.b.H

• Name: Clinical Research & Development
• Affiliation: Octapharma Pharmazeutika Produktionsges.m.b.H

Key inclusion & exclusion 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) is required as part of routine clinical care;
• the 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:
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, or disseminated intravascular coagulation within 3 months of enrollment.
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 heparin of any type or any non-VKA anticoagulant within 24 hours prior to enrollment into the study or with potential need to receive these medications 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 with a known history of hypersensitivity to plasma-derived products.
11. Patients with acute major bleeding or polytrauma.
12. Pregnant or nursing women.
13. Patients participating in another interventional clinical study currently or during the past 30 day prior to enrollment into this study.
14. Patients previously enrolled in this study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Reversal of vitamin K antagonist (VKA) induced anticoagulation in patients needing urgent surgery associated with significant bleeding risk.
MedDRA version: 19.1 Level: PT Classification code 10065667 Term: Haemorrhage prophylaxis System Organ Class: 10042613 - Surgical and medical procedures

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

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: 37224-63-8
Other descriptive name: PROTHROMBIN COMPLEX CONCENTRATES
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 500-

Trade Name: Beriplex
Product Name: Beriplex
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: PROTHROMBIN COMPLEX CONCENTRATE
CAS Number: 37224-63-8
Other descriptive name: PROTHROMBIN COMPLEX CONCENTRATES
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

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).

Primary end point(s): The primary efficacy endpoint is the hemostatic efficacy rating at the end of the surgery.

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.

Timepoint(s) of evaluation of this end point: End of surgery.

Secondary Outcome(s)

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

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

Secondary ID(s)

2016-002649-41-DE

LEX-209

Source(s) of Monetary Support

Octapharma Pharmazeutika Produktionsges.m.b.H