Kcentra Safety and Efficacy Studies

Safety Studies

Safety data for Kcentra were compiled from 2 randomized, plasma-controlled, non-inferiority trials; one evaluated patients with acute major bleeding and the other evaluated patients requiring urgent surgery or other invasive procedures.

The most frequent (≥2.8%) adverse reactions observed in subjects receiving Kcentra were headache, nausea/vomiting, hypotension, and anemia. The most serious adverse reactions were thromboembolic events, including stroke, pulmonary embolism and deep vein thrombosis.

Efficacy Studies

Acute Major Bleeding Trial

Efficacy of Kcentra was measured against that of plasma for rapid reversal of VKA-induced coagulopathy in patients presenting with major bleeding and an elevated INR of ≥ 2.0 within 3 hours before study treatment. The study was a prospective, randomized, open-label, active-controlled, multicenter non-inferiority trial.3

Efficacy of Kcentra was measured against that of plasma for rapid reversal of VKA-induced coagulopathy in patients with major bleeding

The primary endpoint was hemostatic efficacy measured up to 24 hours from the start of infusion. An additional endpoint was the reduction of INR to ≤1.3 at 30 minutes after the end of infusion.

  • Kcentra met the efficacy endpoint of hemostatic efficacy over 24 hours from start of infusion, demonstrating non-inferiority versus plasma.
  • Kcentra also met the additional endpoint for INR reduction to ≤1.3 at 30 minutes after the end of infusion, and demonstrated superiority versus plasma for this endpoint.
  • The relationship between INR values and clinical hemostasis in patients has not been established.

Urgent Surgery / Invasive Procedures Trial

Efficacy of Kcentra was also measured against that of plasma for rapid reversal of VKA-induced coagulopathy in patients needing urgent surgery or an invasive procedure. The study was a prospective, randomized, open‐label, active‐controlled, multicenter non-inferiority trial.

Efficacy of Kcentra was measured against that of plasma for rapid reversal of VKA-induced coagulopathy in patients needing urgent surgery / invasive procedure

The primary endpoint was hemostatic efficacy in preventing excessive hemorrhages during emergency surgical interventions, from the start of infusion until the end of urgent procedure.
An additional outcome measure was the proportion of subjects who had a rapid decrease of INR, defined as an INR value of 1.3 or less 30 minutes after the end of the infusion.

  • Effective hemostasis was achieved by 89.7% of patients in the Kcentra group and 75.3% of patients in the plasma group.
  • Kcentra also met the INR reduction endpoint and was superior to plasma (55.2% of patients achieved early INR reduction in the Kcentra group versus 9.9% in the plasma group).
  • The relationship between INR values and clinical hemostasis in patients has not been established.

Contraindications

Kcentra is contraindicated in:

  • Patients with known anaphylactic or severe systemic reactions to Kcentra or any components in Kcentra including heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III and human albumin.
  • Patients with disseminated intravascular coagulation (DIC).
  • Patients with known heparin-induced thrombocytopenia (HIT). Kcentra contains heparin.

Warnings and Precautions

WARNING: ARTERIAL AND VENOUS THROMBOEMBOLIC COMPLICATIONS

Patients being treated with Vitamin K antagonist therapy have underlying disease states that predispose them to thromboembolic events. Potential benefits of reversing VKA should be weighed against the risk of thromboembolic events, especially in patients with history of such events. Resumption of anticoagulation therapy should be carefully considered once the risk of thromboembolic events outweighs the risk of acute bleeding. Both fatal and nonfatal arterial and venous thromboembolic complications have been reported in clinical trials and postmarketing surveillance. Monitor patients receiving Kcentra, and inform them of signs and symptoms of thromboembolic events. Kcentra was not studied in subjects who had a thromboembolic event, myocardial infarction, disseminated intravascular coagulation, cerebral vascular accident, transient ischemic attack, unstable angina pectoris, or severe peripheral vascular disease within the prior 3 months. Kcentra might not be suitable for patients with thromboembolic events in the prior 3 months.

Hypersensitivity reactions to Kcentra may occur. If patient experiences severe allergic or anaphylactic type reactions, discontinue administration and institute appropriate treatment.

Kcentra is derived from human plasma. The risk of transmission of infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent, cannot be completely eliminated. The safety and efficacy of Kcentra in pediatric use have not been studied. Kcentra should be used in women who are pregnant only if clearly needed.

Kcentra Formulary Kit

Important product information for Kcentra, including disease state, in-depth review of clinical study results and safety information.

Home About Kcentra Safety & Efficacy
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Important Safety Information

Kcentra®, Prothrombin Complex Concentrate (Human), is a blood coagulation factor replacement product indicated for the urgent reversal of acquired coagulation factor deficiency induced by Vitamin K antagonist (VKA—eg, warfarin) therapy in adult patients with acute major bleeding or the need for urgent surgery or other invasive procedure. Kcentra is for intravenous use only.

WARNING: ARTERIAL AND VENOUS THROMBOEMBOLIC COMPLICATIONS

Patients being treated with Vitamin K antagonist therapy have underlying disease states that predispose them to thromboembolic events. Potential benefits of reversing VKA should be weighed against the risk of thromboembolic events, especially in patients with history of such events. Resumption of anticoagulation therapy should be carefully considered once the risk of thromboembolic events outweighs the risk of acute bleeding. Both fatal and nonfatal arterial and venous thromboembolic complications have been reported in clinical trials and postmarketing surveillance. Monitor patients receiving Kcentra, and inform them of signs and symptoms of thromboembolic events. Kcentra was not studied in subjects who had a thromboembolic event, myocardial infarction, disseminated intravascular coagulation, cerebral vascular accident, transient ischemic attack, unstable angina pectoris, or severe peripheral vascular disease within the prior 3 months. Kcentra might not be suitable for patients with thromboembolic events in the prior 3 months.

Kcentra is contraindicated in patients with known anaphylactic or severe systemic reactions to Kcentra or any of its components (including heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III and human albumin). Kcentra is also contraindicated in patients with disseminated intravascular coagulation. Because Kcentra contains heparin, it is contraindicated in patients with heparin-induced thrombocytopenia (HIT).

Hypersensitivity reactions to Kcentra may occur. If patient experiences severe allergic or anaphylactic type reactions, discontinue administration and institute appropriate treatment.

In clinical trials, the most frequent (≥2.8%) adverse reactions observed in subjects receiving Kcentra were headache, nausea/vomiting, hypotension, and anemia. The most serious adverse reactions were thromboembolic events, including stroke, pulmonary embolism and deep vein thrombosis.

Kcentra is made from human blood and may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent.

Please see full prescribing information for Kcentra.

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CSL Behring
Kcentra is manufactured by CSL Behring GmbH and distributed by CSL Behring LLC.
Kcentra® and Beriplex® are registered trademarks of CSL Behring GmbH.
Biotherapies for Life® is a registered trademark of CSL Behring LLC
All other products mentioned are trademarks or registered trademarks of their respective companies.
© 2017 CSL Behring. The product information presented on this site is intended for US residents only.
KCT15-11-0051 12/2015