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 - 23/10/19
, Jordi Navarro-Puerto, MSc b, Shankar Lakshman, MD c, Sonia Singla, MD c, Charles Cousar, MD d, Robin Kim, MD, FACS e, Alan Villavicencio, MD f, Levester Kirksey, MD g, Jaume Ayguasanosa, MD bon behalf of the
Clinical Investigation Study Group on Topical Thrombin (Human) Grifols in Surgery
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.
Le texte complet de cet article est disponible en PDF.Abbreviations and Acronyms : AE, AR, BT-JMI, FV, ITT, mITT, T3, T4, T5, TBS, TClosure, TEAE, TStart, TTH-Grifols
Plan
| Disclosure Information: This study was funded byGrifols, 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 fromGrifols. Drs Ayguasanosa and Navarro-Puerto are employed by Grifols. Dr Villavicencio received research funding fromGrifols, paid to his institution. Dr Minkowitz's institution receives clinical trial grant money from Research Concepts, GP LLC. |
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| Disclosures outside the scope of this work: Dr Villavicencio received honoraria from Leading Edge Spinal Implants and received research funding fromPfizer,Empirical Spine, andGlobus 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. |
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| ClinicalTrials.gov identifier NCT02014402. |
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| ICMJE data-sharing statement available online as eDocument 1. |
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| Members of the Clinical Investigation Study Group on Topical Thrombin (Human) Grifols in Surgery who co-authored the manuscript are listed in the Appendix. |
Vol 229 - N° 5
P. 497 - novembre 2019 Retour au numéro
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