(rivaroxaban)
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XARELTO® (rivaroxaban)
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XARELTO - Reversal Agents in Human Studies - PCC - Levi et al (2014)
Last updated : 05/16/2024
Levi et al (2014) conducted a randomized, open-label, single-center, parallel-group study to investigate the effects of 2 different PCC products, Beriplex® P/N (a 4-factor PCC) and Profilnine® SD (a 3-factor PCC), for the reversal of the pharmacodynamic activity of XARELTO in healthy subjects.1
Three-factor PCC administration produced an increase in the ETP AUC, which surpassed baseline levels 2-4 hours after PCC administration and continued to increase over the measurement period. Following 3-factor PCC administration, mean AUC values surpassed prestudy levels 6-8 hours after PCC administration.1
Study Design1
Enrollment1
Thirty-five subjects were enrolled:
- Thirty-four subjects completed the study
- One subject withdrew consent
Baseline Characteristics1
Efficacy Results
PT: After XARELTO administration, the mean maximum PT value was ~21 seconds at steady state. While PT prolongation varied depending on PT reagent used, the effects of PCC were consistent within 30 minutes.1
Four-factor PCC reduced the mean PT by 2.5-3.5 seconds within the first 30 minutes. Mean PT values continued to decrease until approximately 12 hours after the XARELTO dose (or 8 hours after the PCC dose). After this time, the PT values with PCC were similar to those with saline.1
Three-factor PCC reduced PT by 0.6-1.0 seconds within the first 30 minutes.1
ETP: Three-factor PCC more rapidly reversed XARELTO-induced changes in ETP than 4-factor PCC.1
- ETP, as measured by AUC, decreased over the 4 hours after administration of the last XARELTO dose.
- Three-factor PCC administration produced an increase in the ETP AUC, which surpassed baseline levels 2-4 hours after PCC administration and continued to increase over the measurement period. Following 3-factor PCC administration, mean AUC values surpassed prestudy levels 6-8 hours after PCC administration.
Thrombin levels: After XARELTO administration, maximum thrombin levels were decreased. The administration of 4-factor PCC did not increase maximum thrombin levels. After administration of PCC, maximum thrombin levels returned to prestudy baseline values slowly at first, with a larger and faster increase in thrombin generation occurring about 4 hours after PCC administration, particularly after 3-factor PCC.1
Lag time: XARELTO prolonged the lag time by approximately 2-3 minutes. The administration of PCC did not influence the XARELTO-induced prolongation of the lag time.1
Anti–factor Xa and aPTT: The administration of either PCC product did not alter mean anti–factor Xa values, and neither PCC product reversed XARELTO-induced prolongation of aPTT.1
Safety Results
TEAEs occurred in 51.4% of patients.1
Most common TEAEs included abdominal discomfort, gingival bleeding, back pain, and headache (8.6% each).1
Thromboembolic events: There were no clinically evident thromboembolic events after the administration of PCC.1
aFour hours after XARELTO dosing.
bPT (using STA Neoplastin® and Thromborel® S) and ETP were measured before and after PCC or saline administration.
aPTT, activated partial thromboplastin time; AUC, area under the curve; BMI, body mass index; ETP, endogenous thrombin potential; PCC, prothrombin complex concentrate; PT, prothrombin time; TEAE, treatment-emergent adverse event.
aFour hours after XARELTO dosing.
bPT (using STA Neoplastin® and Thromborel® S) and ETP were measured before and after PCC and saline administration.
AUC, area under curve; BMI, body mass index; ETP, endogenous thrombin potential; IU, international unit; PCC, prothrombin complex concentrate; PT, prothrombin time.
Reference
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1. Levi M, Moore K, Castillejos C, et al. Comparison of three-factor and four-factor prothrombin complex concentrates regarding reversal of the anticoagulant effects of rivaroxaban in healthy volunteers. J Thromb Haemost. 2014;12(9):1428-1436.
