Journal of the American College of Surgeons
Volume 209, Issue 1 , Pages 68-74 , July 2009

A Phase 3b, Open-Label, Single-Group Immunogenicity and Safety Study of Topical Recombinant Thrombin in Surgical Hemostasis

  • Neil K. Singla, MD

      Affiliations

    • Lotus Clinical Research, Huntington Memorial Hospital, Pasadena, CA
    • ,
  • Jeffrey L. Ballard, MD, FACS

      Affiliations

    • Vascular and Interventional Specialists of Orange County, Inc, Orange, CA
    • ,
  • Gregory Moneta, MD, FACS

      Affiliations

    • Oregon Health and Science University, Portland, OR
    • ,
  • C. Duane Randleman Jr, MD

      Affiliations

    • Cardio Thoracic Surgeons, PC, Birmingham, AL
    • ,
  • Kenneth L. Renkens, MD, FACS

      Affiliations

    • Indiana Spine Group, Indianapolis, IN
    • ,
  • W. Allan Alexander, MD

      Affiliations

    • ZymoGenetics, Inc, Seattle, WA
    • Corresponding Author InformationCorrespondence address: W Allan Alexander, MD, ZymoGenetics, Inc, 1201 Eastlake Ave E, Seattle, WA 98102

Received 4 February 2009 ,Revised 4 February 2009 ,Accepted 9 March 2009.

References 

  1. Wolberg AS. Thrombin generation and fibrin clot structure. Blood Rev. 2007;21:131–142
  2. Lawson JH. The clinical use and immunologic impact of thrombin in surgery. Semin Thromb Hemost. 2006;32(Suppl 1):98–110
  3. ZymoGenetics, Inc.. Prescribing information: RECOTHROM. 2008;
  4. Chapman WC, Singla N, Genyk Y, et al. A phase 3, randomized, double-blind comparative study of the efficacy and safety of topical recombinant human thrombin and bovine thrombin in surgical hemostasis. J Am Coll Surg. 2007;205:256–265
  5. Weaver FA, Lew W, Granke K, et al. A comparison of recombinant thrombin to bovine thrombin as a hemostatic ancillary in patients undergoing peripheral arterial bypass and arteriovenous graft procedures. J Vasc Surg. 2008;47:1266–1273
  6. Greenhalgh DG, Gamelli RL, Collins J, et al. A phase 2 multicenter study of the safety and immunogenicity of recombinant thrombin (rThrombin) applied following burn wound excision prior to skin grafting. J Burn Care Res. 2008;29:S56
  7. Lockstadt H, Lawson J, Chapman W, et al. Safety, immunogenicity, and efficacy of recombinant human thrombin as a topical surgical hemostat: integrated results for a multi-surgery phase 2 program; Abstract. J Thromb Haemost. 2005;3(Suppl 1):P1441
  8. Greenhalgh DG, Gamelli RL, Collins J, et al. Recombinant thrombin: safety and immunogenicity in burn wound excision and grafting. J Burn Care Res. 2009;30:371–379
  9. Dorion RP, Hamati HF, Landis B, et al. Risk and clinical significance of developing antibodies induced by topical thrombin preparations. Arch Pathol Lab Med. 1998;122:887–894
  10. 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
  11. 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
  12. Ortel TL, Charles LA, Keller FG, et al. Topical thrombin and acquired coagulation factor inhibitors: clinical spectrum and laboratory diagnosis. Am J Hematol. 1994;45:128–135
  13. King Pharmaceuticals Inc.. Prescribing Information: Thrombin-JMI. 2007;
  14. Agresti A, Min Y. On small-sample confidence intervals for parameters in discrete distributions. Biometrics. 2001;57:963–971
  15. US Census Bureau. B02001. RACE−Universe: total population. Data Set: 2006 American Community Survey. Survey: American Community Survey. http://factfinder.census.gov/servlet/DTTable?_bm=y&-geo_id=01000US&-ds_name=ACS_2006_EST_G00_&-mt_name=ACS_2006_EST_G2000_B02001Accessed October 27, 2008.
  16. Koren E, Zuckerman AL, Mire-Sluis AR. Immune responses to therapeutic proteins in humans—clinical significance, assessment and prediction. Curr Pharm Biotechnol. 2002;3:349–360

 Disclosure Information: The clinical study was funded by ZymoGenetics, Inc. Dr Alexander is employed by ZymoGenetics, Inc as medical director, and the remaining authors were clinical investigators for this study.

 The ClinicalTrials.gov identifier for this study is NCT00491608.

PII: S1072-7515(09)00325-1

doi: 10.1016/j.jamcollsurg.2009.03.016

Journal of the American College of Surgeons
Volume 209, Issue 1 , Pages 68-74 , July 2009

Article Tools

* Image Usage & Resolution