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Vitamin K Antagonist Reversal for Urgent Surgery Using 4F-PCC
LEX 209 Trial
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LEX 209 was a Phase 3, double-blind, noninferiority randomized clinical trial, comparing two four-factor prothrombin complex concentrate (octaplex®) for rapid VKA reversal before urgent surgery.
Primary objective
To evaluate whether the haemostatic efficacy of an investigational 4F-PCC (octaplex) was non-inferior to a control 4F-PCC in rapidly reversing VKA prior to urgent surgery.
Patients
208 adult patients (median age 67.5 years, 118 men, 90 women, 74.5% aged >60 years) on VKA randomized 1:1 with an international normalized ratio (INR) ≥2.0 and needing urgent surgery carrying significant bleeding risk (≥50 mL).
Baseline characteristics of the ITT population were similar between the treatment groups.
Interventions
Single intravenous infusion was dosed by body weight and baseline INR. A dose of 25, 35, or 50 IU/kg of investigational 4F-PCC or control 4F-PCC was administered for baseline INR of 2 to less than 4, 4 to 6, or over 6, respectively.
Efficacy
The primary end point was hemostatic efficacy at surgery end.
Table 1: Hemostatic Efficacy Assessment by the Independent End Point Adjudication Board.
Assessment | Patients, No. (%) Octaplex® (n = 105) | Patients, No. (%) Control (4F-PCC, CSL Behring) (n = 103) |
|---|---|---|
Dichotomous hemostasis (a) | ||
Effective | 97 (94.2) | 99 (94.3) |
Ineffective | 6 (5.7) | 6 (5.8) |
Global hemostatic efficacy observed | ||
Excellent | 41 (39.0) | 50 (48.5) |
Good | 58 (55.2) | 47 (45.6) |
Moderate | 6 (5.7) | 6 (5.8) |
None | 0 (0) | 0 (0) |
Abbreviation: 4F-PCC, 4-factor prothrombin complex concentrate.
a Ratings of excellent and good were considered to be effective hemostasis, whereas ratings of moderate and none were considered to be ineffective hemostasis. Imputation for ineffective was performed for missing rating or additional coagulation therapy after initial investigational medicinal product infusion as none.
An INR of 1.5 or lower at 30 minutes after infusion occurred in 78.1% of patients in the investigational group vs 71.8% of patients in the control group (proportion difference, 0.063; 95% CI, −0.056 to 0.181).
Safety
Similar proportions of patients in the investigational and control groups experienced treatment-emergent adverse events and drug-related TEAEs.
Reference:
Sarode R, Goldstein JN, Simonian G, Hinterberger D, Matveev D, Gareis M, Milling TJ Jr. 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. doi: 10.1001/jamanetworkopen.2024.24758. PMID: 39088218; PMCID: PMC11294963. [PubMed]
