Prospective, Randomized, Phase II, non-Inferiority Study to Evaluate the Safety and Efficacy of Topical Thrombin (Human) Grifols as Adjunct to Hemostasis during Vascular, Hepatic, Soft Tissue, and Spinal Open Surgery.

BACKGROUND: Thrombin-based formulations have been used for topical hemostasis in surgery for decades. However, the number of randomized clinical trials comparing bovine vs. human thrombin is limited.

STUDY DESIGN: A randomized, double-blind, non-inferiority phase-II study evaluated the hemostatic efficacy and safety of plasma-derived Topical Thrombin (Human) Grifols (TTH-Grifols) vs. Bovine Thrombin JMI® (BT-JMI) (2:1 ratio) in vascular, hepatic, soft tissue, and spinal surgeries. The primary efficacy endpoint was the percentage of patients achieving hemostasis at target bleeding sites with mild-moderate bleeding (response) within 5 minutes (T5 ) of treatment application. Non-inferiority was met if the lower limit of the 95% CI of the response ratio of TTH-Grifols relative to BT-JMI by T5 exceeded 0.8. Secondary efficacy variables were the cumulative response by 3 and 4 minutes (T3 , T4 ), and the number of treatment failures. Safety parameters were assessed.

RESULTS: Randomized patients in TTH-Grifols and BT-JMI groups were n=137 and n=68, respectively. In modified intention-to-treat population, rates of hemostasis by T5 were 78.3% (94/120) in TTH-Grifols and 80.3% (49/61) in BT-JMI (response ratio: 0.973; 95% CI: 0.833, 1.135). Rates of hemostasis in vascular, hepatic, soft tissue, and spinal surgeries ranged 75.0%-82.5% for TTH-Grifols, and 54.5%-91.7%, respectively, for BT-JMI. No significant differences in adverse events were observed between treatment groups. Antibodies to bovine factor V antigen were detected in two patients exposed to BT-JMI and in none exposed to TTH-Grifols.

CONCLUSIONS: TTH-Grifols was safe and well tolerated as a local hemostatic agent and was non-inferior to BT-JMI. No TTH-Grifols-treated patients developed antibodies to thrombin.