LEX-209
Trial question
Is investigational four-factor prothrombin complex concentrate noninferior to control four-factor prothrombin complex concentrate in patients requiring urgent surgery with considerable bleeding risk?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
43.0% female
57.0% male
N = 208
208 patients (90 female, 118 male)
Inclusion criteria: adult patients taking VKAs who had an INR ≥ 2 and required urgent surgery with considerable bleeding risk
Key exclusion criteria: life expectancy < 48 hours; surgery or procedure associated with a very low bleeding risk; history of thromboembolic events, myocardial infarction, unstable angina pectoris, or critical aortic stenosis; congenital bleeding disorder; antiphospholipid syndrome
Interventions
N=105 investigational 4F-PCC (single intravenous infusion of an investigational four-factor prothrombin complex concentrate product [Octaplex®])
N=103 control 4F-PCC (single intravenous infusion of a US FDA-approved four-factor prothrombin complex concentrate product [Kcentra®])
Primary outcome
Effective hemostasis
94.3
94.2
94.3 %
70.7 %
47.1 %
23.6 %
0.0 %
Investigational
4F-PCC
Control
4F-PCC
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority margin in effective hemostasis (94.3% vs. 94.2%; PD 0.001, 95% CI -0.08 to 0.08)
Secondary outcomes
Borderline significant decrease in INR ≤ 1.5 at 30 minutes after infusion (78.1% vs. 71.8%; PD 0.063, 95% CI -0.06 to 0.18)
Borderline significant decrease in RBC transfusion during surgery (3.8% vs. 2.9%; PD 0.009, 95% CI -0.07 to 0.09)
Significant increase in improvement in mean activity of factor VII at 30 minutes post-infusion (40.9% vs. 32.8%; MD 8, 95% CI 2 to 15)
Safety outcomes
No significant differences in treatment-emergent adverse events, thrombotic events, and death.
Conclusion
In adult patients taking VKAs who had an INR ≥ 2 and required urgent surgery with considerable bleeding risk, investigational 4F-PCC was noninferior to control 4F-PCC with respect to effective hemostasis.
Reference
Ravi Sarode, Joshua N Goldstein, Gregory Simonian et al. Vitamin K Antagonist Reversal for Urgent Surgery Using 4-Factor Prothrombin Complex Concentrates: A Randomized Clinical Trial. JAMA Netw Open. 2024 Aug 1;7(8):e2424758.
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