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Study of Octaplex, a Four-factor Prothrombin Complex Concentrate (4F-PCC) and Beriplex® P/N (Kcentra) for the Reversal of Vitamin K Antagonist (VKA) Induced Anticoagulation in Patients Needing Urgent Surgery With Significant Bleeding Risk.

Primary Purpose

Significant Bleeding Risk

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Octaplex

Beriplex P/N (Kcentra)

About this trial

This is an interventional treatment trial for Significant Bleeding Risk focused on measuring anticoagulant reversal, urgent surgery, invasive procedures, vitamin K, prothrombin complex concentrate, four-factor prothrombin complex concentrate (4F-PCC)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

Male or female patients at least 18 years of age.
Patients currently on oral anticoagulation treatment with VKA of coumadin or warfarin type.
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;
Patients with an international normalized ratio (INR) of 2.0 or above at the time of decision to reverse the anticoagulation status.
Patients who have given written informed consent and who are able and willing to comply with the procedures described in the study protocol.

Exclusion Criteria

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).
Patients for whom the planned surgery or procedure is commonly associated with a very low bleeding risk (e.g. catheter placement, gastroscopy).
Patients with a history of thromboembolic events (TEEs), myocardial infarction, unstable angina pectoris, critical aortic stenosis, cerebrovascular accident, transient ischemic attack, severe peripheral vascular disease, or disseminated intravascular coagulation within 3 months of enrollment.
Patients with a known congenital bleeding disorder.
Patients with a known antiphospholipid antibody syndrome.
Patients with present or past specific factor inhibitor activity.
Patients with thrombocytopenia of <80,000/μL or history of heparin-induced thrombocytopenia.
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.
Patients who have received prothrombin complex concentrates (PCCs), fresh frozen plasma or vitamin K within 72 hours prior to enrollment into the study.
Patients with a known history of hypersensitivity to plasma-derived products.
Patients with acute major bleeding or polytrauma.
Pregnant or nursing women.
Patients participating in another interventional clinical study currently or during the past 30 days prior to enrollment into this study.
Patients previously enrolled in this study.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Octaplex

Beriplex P/N (Kcentra)

Arm Description

Participants to receive1 Octaplex infusion intravenously

Participants to receive1 Kcentra infusions intravenously

Outcomes

Primary Outcome Measures

Hemostatic Efficacy Rating by IEAB

Hemostatic Efficacy rated by the Independent Endpoint Adjudication Committee based on a 1 to 4 point hemostatic efficacy scale, taking into account blood loss and transfusion requirements in the context of the surgery. Hemostatic efficacy was assessed based on objective criteria in the categories 'excellent', 'good', 'moderate', or 'none'. Ratings of 'excellent' and 'good' were considered as 'effective' hemostasis, while ratings of 'moderate' and 'none' were considered as 'ineffective' hemostasis.

Dichotomous Hemostasis Success

To demostrate clinical non-inferiority of treatment with Octaplex to treatment with Beriplex P/N (Kcentra) with respect to hemostatic success. Effective hemostatis includes Excellent and Good ratings, while Ineffective hemostasis includes Moderate, None and missing ratings from Global hemostatic efficacy observed by IEAB

Secondary Outcome Measures

Measuring of International Normalized Ratio (INR) to ≤ 1.5

Number of patients with an international normalized ratio (INR) value of less or equal to 1.5 at 30 min (± 15 min) after the end of infusion.

Coagulation Factor II Levels

Change in coagulation factor levels from baseline to after the end of infusion using the Hodges-Lehmann Estimator for median differences: o Factor II The Hodges-Lehmann Estimator is a method of robust estimation. This estimator is used to give an estimate of the difference between the values in two sets of data. If the two sets of data contain m and n data points respectively, m × n pairs of points (one from each set) can be formed and each pair gives a difference of values. The Hodges-Lehmann estimator for the difference is defined as the median of the m × n differences.

Coagulation Factor VII Levels

Change in coagulation factor levels from baseline to after the end of infusion using the Hodges-Lehmann Estimator for median differences: o Factor VII The Hodges-Lehmann Estimator is a method of robust estimation. This estimator is used to give an estimate of the difference between the values in two sets of data. If the two sets of data contain m and n data points respectively, m × n pairs of points (one from each set) can be formed and each pair gives a difference of values. The Hodges-Lehmann estimator for the difference is defined as the median of the m × n differences.

Coagulation Factor IX Levels

Change in coagulation factor levels from baseline to after the end of infusion using the Hodges-Lehmann Estimator for median differences: o Factor II Factor IX The Hodges-Lehmann Estimator is a method of robust estimation. This estimator is used to give an estimate of the difference between the values in two sets of data. If the two sets of data contain m and n data points respectively, m × n pairs of points (one from each set) can be formed and each pair gives a difference of values. The Hodges-Lehmann estimator for the difference is defined as the median of the m × n differences.

Coagulation Factor X Levels

Change in coagulation factor levels from baseline to after the end of infusion using the Hodges-Lehmann Estimator for median differences: o Factor X The Hodges-Lehmann Estimator is a method of robust estimation. This estimator is used to give an estimate of the difference between the values in two sets of data. If the two sets of data contain m and n data points respectively, m × n pairs of points (one from each set) can be formed and each pair gives a difference of values. The Hodges-Lehmann estimator for the difference is defined as the median of the m × n differences.

Number of Patients Requiring Red Blood Cells (RBC)

Number of patients receiving red blood cells (RBC) during the surgery

Full Information

NCT ID

NCT02740335

First Posted

April 5, 2016

Last Updated

March 6, 2023

Sponsor

Octapharma

1. Study Identification

Unique Protocol Identification Number

NCT02740335

Brief Title

Study of Octaplex, a Four-factor Prothrombin Complex Concentrate (4F-PCC) and Beriplex® P/N (Kcentra) for the Reversal of Vitamin K Antagonist (VKA) Induced Anticoagulation in Patients Needing Urgent Surgery With Significant Bleeding Risk.

Official 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 (VKA) Induced Anticoagulation in Patients Needing Urgent Surgery With Significant Bleeding Risk.

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Completed

Study Start Date

June 8, 2017 (Actual)

Primary Completion Date

February 23, 2022 (Actual)

Study Completion Date

February 23, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Octapharma

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

To demonstrate that the efficacy of OCTAPLEX as a reversal agent in patients under Vitamin K Antagonist (VKA) therapy with the need for urgent surgery with significant bleeding risk is clinically non-inferior to that Beriplex® P/N (Kcentra).

Detailed Description

The primary objective of the study is to demonstrate that the efficacy of OCTAPLEX as a reversal agent in patients under Vitami n K Antagonist (VKA)therapy with the need for urgent surgery with significant bleeding risk is clinically non-inferior to that Beriplex® P/N (Kcentra). The secondary objective of the study is to investigate the safety and tolerability of OCTAPLEX compared to Beriplex® P/N (Kcentra) in patients under Vitamin K Antagonist (VKA) therapy with the need for urgent surgery with significant bleeding risk.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Significant Bleeding Risk

Keywords

anticoagulant reversal, urgent surgery, invasive procedures, vitamin K, prothrombin complex concentrate, four-factor prothrombin complex concentrate (4F-PCC)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

208 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Octaplex

Arm Type

Experimental

Arm Description

Participants to receive1 Octaplex infusion intravenously

Arm Title

Beriplex P/N (Kcentra)

Arm Type

Active Comparator

Arm Description

Participants to receive1 Kcentra infusions intravenously

Intervention Type

Drug

Intervention Name(s)

Octaplex

Other Intervention Name(s)

4F PCC, 4 Factor PCC, 4 Factor Prothrombin Concentrate Complex

Intervention Description

OCTAPLEX will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).

Intervention Type

Drug

Intervention Name(s)

Beriplex P/N (Kcentra)

Other Intervention Name(s)

Kcentra

Intervention Description

Beriplex® P/N (Kcentra) will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).

Primary Outcome Measure Information:

Title

Hemostatic Efficacy Rating by IEAB

Description

Time Frame

At the end of the surgery

Title

Dichotomous Hemostasis Success

Description

Time Frame

At the end of surgery

Secondary Outcome Measure Information:

Title

Measuring of International Normalized Ratio (INR) to ≤ 1.5

Description

Number of patients with an international normalized ratio (INR) value of less or equal to 1.5 at 30 min (± 15 min) after the end of infusion.

Time Frame