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Clinical Trial
. 2019 Nov;229(5):497-507.e1.
doi: 10.1016/j.jamcollsurg.2019.07.008. Epub 2019 Jul 31.

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

Harold Minkowitz  1 , Jordi Navarro-Puerto  2 , Shankar Lakshman  3 , Sonia Singla  3 , Charles Cousar  4 , Robin Kim  5 , Alan Villavicencio  6 , Levester Kirksey  7 , Jaume Ayguasanosa  2 ; Clinical Investigation Study Group on Topical Thrombin (Human) Grifols in Surgery
Collaborators, Affiliations
Clinical Trial

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

Harold Minkowitz et al. J Am Coll Surg. 2019 Nov.

Abstract

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; Instituto Grifols SA) vs bovine THROMBIN JMI (BT-JMI; GenTrac Inc) (2:1 ratio) in vascular, hepatic, soft tissue, and spinal operations. The primary efficacy end point was the percentage of patients achieving hemostasis at target bleeding sites with mild to 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 and 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 of 120) in TTH-Grifols and 80.3% (49 of 61) in BT-JMI (response ratio: 0.973; 95% CI 0.833 to 1.135). Rates of hemostasis in vascular, hepatic, soft tissue, and spinal operations ranged from 75.0% to 82.5% for TTH-Grifols and from 54.5% to 91.7% for BT-JMI. No significant differences in adverse events were observed between treatment groups. Antibodies to bovine factor V antigen were detected in 2 patients exposed to BT-JMI and in none exposed to TTH-Grifols.

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

Trial registration: ClinicalTrials.gov NCT02014402.

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