Journal of the American College of Surgeons
Volume 205, Issue 2 , Pages 256-265 , August 2007

A Phase 3, Randomized, Double-Blind Comparative Study of the Efficacy and Safety of Topical Recombinant Human Thrombin and Bovine Thrombin in Surgical Hemostasis

  • William C. Chapman, MD, FACS

      Affiliations

    • Department of Surgery, Washington University, St Louis School of Medicine, St Louis, MO
    • Corresponding Author InformationCorrespondence address: William C Chapman, MD, Washington University, Department of Surgery, Section of Transplantation, 660 South Euclid Ave, Campus Box 8109, Room 6107 Queeny Tower, St Louis, MO 63110.
    • ,
  • Neil Singla, MD

      Affiliations

    • Huntington Memorial Hospital, Pasadena, CA
    • ,
  • Yuri Genyk, MD, FACS

      Affiliations

    • USC Healthcare Consultation Center, University of Southern California, Los Angeles, CA
    • ,
  • James W. McNeil, MD, FACS

      Affiliations

    • Vascular Surgery Associates, Baton Rouge, LA
    • ,
  • Kenneth L. Renkens Jr, MD, FACS

      Affiliations

    • Indiana Spine Group, Indianapolis, IN
    • ,
  • Thomas C. Reynolds, MD, PhD

      Affiliations

    • ZymoGenetics Inc, Seattle, WA
    • ,
  • Aileen Murphy, MPH

      Affiliations

    • ZymoGenetics Inc, Seattle, WA
    • ,
  • Fred A. Weaver, MD, FACS

      Affiliations

    • USC Healthcare Consultation Center, University of Southern California and LA County Hospital, Los Angeles, CA.

Received 27 February 2007 ,Accepted 5 March 2007.

References 

  1. Lawson JH. The clinical use and immunologic impact of thrombin in surgery. Semin Thromb Hemost. 2006;32(Suppl 1):98–110
  2. Nelson PA, Powers JN, Estridge TD, et al. Serological analysis of patients treated with a new surgical hemostat containing bovine proteins and autologous plasma. J Biomed Mater Res. 2001;58:710–719
  3. Winterbottom N, Kuo JM, Nguyen K, et al. Antigenic responses to bovine thrombin exposure during surgery: a prospective study of 309 patients. J Applied Res. 2002;2:1–11
  4. Thrombin-JMI. Bristol, VA: Jones Pharma Incorporated; 2005;[package insert]
  5. Lawson JH, Lynn KA, Vanmatre RM, et al. Antihuman factor V antibodies after use of relatively pure bovine thrombin. Ann Thorac Surg. 2005;79:1037–1038
  6. Ortel TL, Mercer MC, Thames EH, et al. Immunologic impact and clinical outcomes after surgical exposure to bovine thrombin. Ann Surg. 2001;233:88–96
  7. Sands JJ, Nudo SA, Ashford RG, et al. Antibodies to topical bovine thrombin correlate with access thrombosis. Am J Kidney Dis. 2000;35:796–801
  8. Sarfati MR, Dilorenzo DJ, Kraiss LW, et al. Severe coagulopathy following intraoperative use of topical thrombin. Ann Vasc Surg. 2004;18:349–351
  9. Savage WJ, Kickler TS, Takemoto CM. Acquired coagulation factor inhibitors in children after topical bovine thrombin exposure. Pediatr Blood Cancer. 2006;[Epub ahead of print]
  10. Schoenecker JG, Hauck RK, Mercer MC, et al. Exposure to topical bovine thrombin during surgery elicits a response against the xenogeneic carbohydrate galactose alpha1-3galactose. J Clin Immunol. 2000;20:434–444
  11. Streiff MB, Ness PM. Acquired FV inhibitors: a needless iatrogenic complication of bovine thrombin exposure. Transfusion. 2002;42:18–26
  12. Chapman WC, Lockstadt H, Singla N, et al. Phase 2, randomized, double-blind, placebo-controlled, multicenter clinical evaluation of recombinant human thrombin in multiple surgical indications. J Thromb Haemost. 2006;4:2083–2085
  13. Burington BE, Emerson SS. Flexible implementations of group sequential stopping rules using constrained boundaries. Biometrics. 2003;59:770–777
  14. Whitehead J. The design and analysis of sequential clinical trials (revised second edition). Chichester, West Sussex, England: John Wiley & Sons Ltd; 1997;
  15. Emerson S, Fleming T. Parameter estimation following group sequential hypothesis testing. Biometrika. 1990;7:875–892
  16. Hall WJ, Liu A. Sequential tests and estimators after overrunning based on maximum-likelihood ordering. Biometrika. 2002;89:699–707
  17. Huber PJ. The behavior of maximum likelihood estimates under nonstandard conditions. Math Statist Prob. 1967;1:221–233
  18. Mire-Sluis AR, Barrett YC, Devanarayan V, et al. Recommendations for the design and optimization of immunoassays used in the detection of host antibodies against biotechnology products. J Immunol Methods. 2004;289:1–16
  19. CoStasis Multi-center Collaborative Writing Committee. A novel collagen-based composite offers effective hemostasis for multiple surgical indications: Results of a randomized controlled trial. Surgery. 2001;129:445–450
  20. Weaver FA, Hood DB, Zatina M, et al. Gelatin-thrombin-based hemostatic sealant for intraoperative bleeding in vascular surgery. Ann Vasc Surg. 2002;16:286–293
  21. Bishop PD, Lewis KB, Schultz J, et al. Comparison of recombinant human thrombin and plasma-derived human alpha-thrombin. Semin Thromb Hemost. 2006;32(Suppl 1):86–97

 Competing Interests Declared: Authors Murphy and Reynolds were employees of ZymoGenetics, the sponsor of the trial; during the entire study. They are no longer employees of ZymoGenetics.Funding for this trial was provided by ZymoGenetics, Inc.Trial Registration: This study is registered with ClinicalTrials.gov with the identifier NCT00245336.

PII: S1072-7515(07)00456-5

doi: 10.1016/j.jamcollsurg.2007.03.020

Journal of the American College of Surgeons
Volume 205, Issue 2 , Pages 256-265 , August 2007

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