Study of Octaplex (Human Prothrombin Complex Concentrate) and Fresh Frozen Plasma in Patients Under Vitamin K Therapy Antagonist Needing Urgent Surgery or Invasive Procedures

• Sponsor: Octapharma
• Information provided by (Responsible Party): Octapharma

Study Description

Brief Summary:

The purpose of this study is to determine whether Octaplex (human prothrombin complex concentrate) can reverse the effects of anticoagulants when compared to the standard treatment of fresh frozen plasma (FFP).

Condition or disease	Intervention/treatment	Phase
Reversal of Anticoagulant Treatment	Biological: Octaplex (human prothrombin complex concentrate); Biological: Fresh frozen plasma	Phase 3

Detailed Description:

The primary objective of the study is to demonstrate that the efficacy of Octaplex as a reversal agent in patients under vitamin K antagonist therapy with the need for urgent surgery or invasive procedures was not clinically inferior to that of FFP.

The secondary objective of the study is to investigate the safety and tolerability of Octaplex compared to FFP in patients under vitamin K antagonist therapy with the need for urgent surgery or invasive procedures.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	200 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Randomized, Open-label, Efficacy and Safety Study of Octaplex and Fresh Frozen Plasma (FFP) in Patients Under Vitamin K Antagonist Therapy With the Need for Urgent Surgery or Invasive Procedures
Study Start Date :	May 2008
Actual Primary Completion Date :	March 2012
Actual Study Completion Date :	August 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: Octaplex (human prothrombin complex concentrate); Participants to receive1 or more Octaplex infusions intravenously until their International Normalized Ratio (INR) was < 1.5.	Biological: Octaplex (human prothrombin complex concentrate); INR is determined 15 minutes after the end of each infusion. Each dose (mL/kg body weight) was calculated as = ln(INR/1.4)/0.52. The maximum dose for initial treatment was not to exceed 5500 IU. If the INR is ≥ 1.5 after the initial infusion, additional infusions will be repeated until the INR was < 1.5. Octaplex (500 units, IU) is supplied in vials and was reconstituted with 20 mL of Water for Injection (Ph.Eur.).
Active Comparator: Fresh frozen plasma; Participants to receive1 or more fresh frozen plasma infusions intravenously until their International Normalized Ratio (INR) was < 1.5.	Biological: Fresh frozen plasma; INR is determined 15 minutes after the end of each infusion. The initial dose is 10 mL/kg for a participant with an initial INR of < 3 and 15 mL/kg for a participant with an initial INR of ≥ 3. If the INR is ≥ 1.5 after the initial infusion, additional infusions of 5 mL/kg will be repeated until the INR was < 1.5. Fresh frozen plasma is supplied by the blood bank at each study site and will be prepared and handled according to the site's standard practice.; Other Name: FFP

Outcome Measures

Primary Outcome Measures :

1. There will be two primary end points in this study. The first primary efficacy endpoint is the correction of INR to < 1.5. [ Time Frame: 15 minutes after the end of first infusion of OCTAPLEX or FFP ]

Secondary Outcome Measures :

1. number of intra-operative red blood cell units (RBC) transfused [ Time Frame: intra-operative ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Male or female patients at least 18 years of age.
• Patients receiving oral anticoagulation with coumadin or warfarin derived agents.
• Patients who have need for urgent surgery or an invasive procedure up to 8 hours after admission or identification of a patient currently hospitalized, where oral or parenteral vitamin K therapy is deemed too slow in its action for reversal of coumadin or warfarin anticoagulant effects.
• Patients with an international normalized ratio (INR) of 2.0 or above.
• Patients who have given written informed consent or for whom written informed consent has been obtained from the patient's legal representative on their behalf.
• Patients able and willing to comply with the procedures laid out in the study protocol. In the case of unconscious and/or incapacitated patients, the willingness of the patient's legal representative for the patient to undergo the procedures laid out in the study protocol.

Exclusion Criteria:

• Patients with a life expectancy of less than 48 hours (eg, patients with a Glasgow Coma Scale (GCS) equal to 3 or a head abbreviated injury score (AIS) of 6, patients requiring continuous inotropic or pressor support, patients status post-cardiac arrest).
• Patients with a history within the last 6 months of disseminated intravascular coagulation (DIC), or hyperfibrinolysis.
• Patients with a known congenital coagulation disorder.
• Patients with known antiphospholipid antibody syndrome or have known lupus anticoagulant antibodies.
• Patients with present or past specific factor inhibitor activity.
• Patients with thrombocytopenia of < 80,000 or a history of heparin induced thrombocytopenia (HIT).
• Patients having received heparin of any type or any non-coumadin or warfarin anticoagulant immediately prior and/or intended to be given within the first 1 hour post-infusion.
• Patients who have received vitamin K more than 3 hours prior to the infusion of study drug.
• Patients with a history of hypersensitivity to plasma-derived products.
• Pregnant or nursing women.
• Patients participating in another clinical treatment study currently or during the past 1 month prior to study inclusion.
• Patients previously enrolled in this study.

Contacts and Locations

Locations

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United States, Pennsylvania
Contact Octapharma for Facility details
Philadelphia, Pennsylvania, United States, 19141

Sponsors and Collaborators

Octapharma

Investigators

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Study Director:	Wolfgang Frenzel, MD	International Medical Director

More Information

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Responsible Party:	Octapharma
ClinicalTrials.gov Identifier:	NCT00618098 History of Changes
Other Study ID Numbers:	LEX-205
First Posted:	February 18, 2008
Last Update Posted:	October 18, 2016
Last Verified:	October 2015

Keywords provided by Octapharma:

anticoagulant reversal; urgent surgery; invasive procedures; vitamin K; prothrombin complex concentrate

Additional relevant MeSH terms:

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Vitamins; Vitamin K; Thrombin; Micronutrients; Nutrients; Growth Substances	Physiological Effects of Drugs; Antifibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Hemostatics; Coagulants