A Prospective, Single-Blind, Randomized, Phase III Study to Evaluate the Safety and Efficacy of Fibrin Sealant Grifols as an Adjunct to Hemostasis During Soft Tissue Open Surgery

摘要

Background/Purpose: Rapid hemostasis, an essential prerequisite of good surgical practice during surgical bleeding, including soft tissue open surgery, often requires adjunctive treatment. We evaluated the safety and hemostatic effectiveness of a human plasma-derived fibrin sealant (FS Grifols) in soft tissue open surgery. Methods: Patients with moderate soft tissue bleeding during open, urologic, gynecologic or general surgery were studied. The trial consisted of a preliminary phase (to familiarize investigators with the technique for FS Grifols application and the intraoperative procedures required by the clinical protocol) and a primary phase: in both phases, patients were randomized 1:1 to FS Grifols or Surgicel (R). The primary efficacy endpoint, based on analysis of subjects in the primary phase of the study, was to evaluate whether FS Grifols was non-inferior to Surgicel (R) in achieving hemostasis, based on the proportion of subjects in both treatment groups who achieved hemostasis at the target bleeding site (TBS) by 4 min (T-4) following the start of treatment application. Safety assessments included adverse events (AEs), vital signs, physical assessments, common clinical laboratory tests, viral markers, and immunogenicity. Results: A total of 224 subjects were randomized (primary phase): FS Grifols (N = 116), Surgicel (R) (N = 108). The 95% CI at T-4 for the ratio of the proportion of patients achieving hemostasis in the two treatment groups was 1.064 (0.934, 1.213), indicating non-inferiority for FS Grifols vs. Surgicel (R). The rate of hemostasis at the TBS by T-4 in both phases of the study was higher in the FS Grifols treatment group (preliminary phase: 90.2%; primary phase: 82.8%) than in the Surgicel (R) treatment group (preliminary phase: 78.8%; primary phase: 77.8%). Overall, reported AEs were as expected in surgical patients and were similar between the two treatment groups. Conclusions: This study shows the non-inferiority in time to hemostasis of FS Grifols vs. Surgicel as an adjunct to hemostasis in patients undergoing soft tissue open surgery, and a similar rate of AEs.