TY - JOUR
T1 - 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
AU - Clinical Investigation Study Group on Topical Thrombin (Human) Grifols in Surgery
AU - Minkowitz, Harold
AU - Navarro-Puerto, Jordi
AU - Lakshman, Shankar
AU - Singla, Sonia
AU - Cousar, Charles
AU - Kim, Robin
AU - Villavicencio, Alan
AU - Kirksey, Levester
AU - Ayguasanosa, Jaume
AU - Anderson, Christopher D.
AU - Labow, Daniel
AU - Fishbein, Thomas
AU - Sheiner, Patricia
AU - Lockstadt, Harry
AU - Courtney, Kecia
AU - Cheng, Junliang
AU - Barrera, Gladis
AU - Henriquez, Waleska T.
N1 - Funding Information:
Disclosure Information: This study was funded by Grifols, the manufacturer of topical thrombin (human) Grifols, Medical writing support was provided by Gines Escolar, MD, PhD, under the direction of the authors, with funding from Grifols. Drs Ayguasanosa and Navarro-Puerto are employed by Grifols. Dr Villavicencio received research funding from Grifols, paid to his institution. Dr Minkowitz's institution receives clinical trial grant money from Research Concepts, GP LLC.Disclosures outside the scope of this work: Dr Villavicencio received honoraria from Leading Edge Spinal Implants and received research funding from Pfizer, Empirical Spine, and Globus Medical, paid to his institution. Dr Minkowitz is a paid consultant to AcelRX, Heron, Avenue, Concentric, Takeda, Sorrento, and Acacia, and receives payment for lecture from AcelRX, Heron, Avenue, Acacia, and Merck.
Publisher Copyright:
© 2019 American College of Surgeons
PY - 2019/11
Y1 - 2019/11
N2 - 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.
AB - 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.
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U2 - 10.1016/j.jamcollsurg.2019.07.008
DO - 10.1016/j.jamcollsurg.2019.07.008
M3 - Article
C2 - 31376435
AN - SCOPUS:85072329671
SN - 1072-7515
VL - 229
SP - 497-507.e1
JO - Journal of the American College of Surgeons
JF - Journal of the American College of Surgeons
IS - 5
ER -