A Prospective, Randomized, Multicenter Clinical Trial on the Safety and Efficacy of a Ready-to-Use Fibrin Sealant as an Adjunct to Hemostasis during Vascular Surgery

Abstract

Background: Anastomotic or "stitch hole" bleeding is common during vascular surgery with synthetic material such as Dacron or polytetrafluoroethylene. Hemostatic adjuncts such as fibrin sealant (FS) may reduce blood loss and operating time in such circumstances. We evaluated the safety and the hemostatic effectiveness of a ready-to-use human plasma-derived FS in vascular surgery.

Methods: Patients with mild/moderate suture line bleeding during elective, open, vascular surgery using synthetic grafts or patches were studied. In an initial Exploratory Study, all patients were treated with FS Grifols, and in a subsequent Primary Study were randomized in a 2:1 ratio to FS Grifols or manual compression (MC). The primary efficacy end point was time to hemostasis (TTH), assessed at defined intervals from the start of treatment application, during a 10-min observational period. Safety end points (in Exploratory + Primary Studies) included adverse events (AEs), vital signs, physical assessments, common clinical laboratory tests (coagulation, complete blood count, serum clinical chemistry parameters, microscopic urinalysis), viral markers, and immunogenicity.

Results: In the Primary Study, the proportion of patients who achieved hemostasis at the 3-min time point was higher in the FS Grifols group (46.4%, n = 51/110) than in the MC group (26.3%, n = 15/57) (P < 0.05). The benefit was maintained at successive time intervals: 69 FS Grifols patients (62.7%) and 18 MC patients (31.6%) at 4 min; 82 FS Grifols patients (74.5%) and 28 MC patients (49.1%) at 5 min. The differences between the groups persisted for TTH ≤ 7 min and TTH ≤ 10 min. Treatment failure was reported for 13 FS Grifols patients (11.8%) and 16 MC patients (28.1%). TTH was shorter after FS Grifols application than after MC application. Differences were statistically significant in favor of FS Grifols for each TTH category and for the overall comparison (P < 0.001) as well as for each TTH category (cumulative) and for treatment failure (P = 0.016). Overall, AE experience and types of AEs reported were those expected in this patient population and were similar between the 2 treatment groups. The most frequently reported AEs were procedural pain (59.9% and 69.2% of patients in the FS Grifols [n = 72 + 111] and MC [n = 57] groups, respectively) and nausea (23.5% and 19.2% of patients, respectively).

Conclusions: FS Grifols was efficacious and safe as an adjunct to anastomotic hemostasis in patients undergoing arterial surgery using prosthetic material with mild to moderate bleeding.