Efficacy

In 2 head-to-head trials, Kcentra demonstrated superiority to plasma in 3 of 4 efficacy endpoints

Efficacy endpoint Urgent Surgery​/​Invasive Procedures trial Acute Major Bleeding trial
Effective hemostasis Kcentra superior Kcentra and plasma equally effective
Early INR reduction Kcentra superior Kcentra superior

Effective hemostasis measured up to 24 hours for the Acute Major Bleeding trial and until the end of procedure (up to 24 hours) for the Urgent Surgery/Invasive Procedures trial.
Rapid INR reduction to ≤1.3 at 0.5 hours after end of infusion.

  • The relationship between INR values and clinical hemostasis in patients has not been established
  • Kcentra was compared to plasma in 2 prospective, randomized, open-label, active-controlled, multicenter, noninferiority trials for urgent warfarin reversal in 388 adult patients with:
Need for urgent surgery/invasive procedure or
Acute major bleeding
Click below to explore Kcentra efficacy

Superior or equally effective hemostasis vs plasma

Superior hemostasis with Kcentra vs plasma in the Urgent Surgery/Invasive Procedures trial.
Equally effective hemostasis with Kcentra vs plasma in the Acute Major Bleeding trial.
Superior hemostasis with Kcentra vs plasma in the Urgent Surgery/Invasive Procedures trial
Kcentra demonstrated superior hemostasis vs plasma in the Urgent Surgery/Invasive Procedures trial

Kcentra–plasma (%) [95% CI] = 14.3 [2.8, 25.8] (prespecified noninferiority margin >–10%; Kcentra superior to plasma as lower limit of 95% CI >0).

*Intent to treat-efficacy (ITT-E) population.

  • Criteria for effective hemostasis were based on:
    • The difference between predicted and actual blood losses
    • Subjective hemostasis rating
    • The need of additional blood products containing coagulation factors
  • Sustained until the end of urgent procedure
SEE STUDY DESIGN
Equally effective hemostasis with Kcentra vs plasma in the Acute Major Bleeding trial
Kcentra demonstrated equally effective hemostasis vs plasma in the Acute Major Bleeding trial

Kcentra–plasma (%) [95% CI] = 7.1 [–5.8, 19.9] (prespecified noninferiority margin >–10%). Farrington–Manning P value for noninferiority, rejecting null hypothesis of inferiority of 4F-PCC.

*ITT-E population

  • Efficacy was adjudicated as “effective” or “not effective” by a blinded independent Endpoint Adjudication Board
  • Criteria for effective hemostasis were based on standard clinical assessments, including:
    • Vital signs
    • Hemoglobin measurements
    • CT assessments at predefined time points
  • Sustained up to 24 hours
SEE STUDY DESIGN
BACK TO DATA

Kcentra pivotal trial study design:
urgent surgery/invasive procedures

Prospective, randomized, open-label, active-controlled, multicenter, noninferiority trial2

Urgent Surgery/Invasive Procedures trial study design
BACK TO DATA

Kcentra pivotal trial study design:
acute major bleeding

Prospective, randomized, open-label, active-controlled, multicenter, noninferiority trial10

Acute Major Bleeding trial study design

Superior early INR reduction vs plasma

Superior speed in reaching INR of ≤1.3 within 30 minutes after end of infusion.
Superior speed in reaching INR of ≤1.3 within 30 minutes after end of infusion
Kcentra demonstrated superior early INR reduction vs plasma
Kcentra demonstrated superior early INR reduction vs plasma

*Kcentra—plasma (%) [95% CI] = 45.3 [31.9, 56.4] for noninferiority (prespecified noninferiority margin >–10% in the Urgent Surgery/Invasive Procedures trial; Kcentra superior to plasma if lower limit 95% CI >0).

Kcentra—plasma (%) [95% CI] = 52.6 [39.4, 65.9] for noninferiority (prespecified noninferiority margin >–10%; Kcentra superior to plasma if lower limit 95% CI >0) in the Acute Major Bleeding trial.

  • The relationship between INR values and clinical hemostasis in patients has not been established
  • Time to INR reduction does not include infusion time. Mean infusion time for Kcentra was under 25 minutes, while mean infusion time for plasma was over 2 hours2,10
  • Administer vitamin K concurrently to patients receiving Kcentra. Vitamin K is administered to maintain vitamin K–dependent clotting factor levels once the effects of Kcentra have diminished

Sustained INR reduction vs plasma

Statistically significant INR reduction sustained for up to 8 hours.
Statistically significant INR reduction sustained for up to 8 hours
Kcentra demonstrated 8 hours of statistically significant INR reduction in the Urgent Surgery/Invasive Procedures trial

*Statistically significant difference compared to plasma by 2-sided Wilcoxon test.

Statistically significant INR reduction sustained for up to 12 hours
Kcentra demonstrated 12 hours of statistically significant INR reduction in the Acute Major Bleeding trial

*Statistically significant difference (P<0.0001) compared to plasma by 2-sided Wilcoxon test.
P=0.0002.

  • Administer vitamin K concurrently to patients receiving Kcentra. Vitamin K is administered to maintain vitamin K–dependent clotting factor levels once the effects of Kcentra have diminished
Top of Page Important Safety Information
Important Safety Information & Indications

Important Safety Information

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 derived from human plasma. The risk of transmission of infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent and its variant (vCJD), cannot be completely eliminated.

Indications

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.

Please see full prescribing information for Kcentra.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

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