Study of Recombinant Human Thrombin for Bleeding During Surgery

• Incidence and severity of adverse events [ Time Frame: Up to 29 days ] [ Designated as safety issue: Yes ]
• Incidence and grade of clinical laboratory abnormalities [ Time Frame: Up to 29 days ] [ Designated as safety issue: Yes ]
• Incidence of anti-product antibodies [ Time Frame: Up to 29 days ] [ Designated as safety issue: Yes ]

• Incidence and severity of adverse events
• Incidence and grade of clinical laboratory abnormalities
• Incidence of anti-product antibodies

The purpose of this study is to determine whether recombinant human Thrombin (rhThrombin) is effective in stopping bleeding during surgery, in comparison with bovine thrombin.

This is a Phase 3 multiple site, randomized, double-blind, controlled trial designed to evaluate the comparative efficacy and safety of rhThrombin and bovine thrombin in patients undergoing spinal surgery, hepatic resection, peripheral arterial bypass surgery, or arteriovenous graft formation for hemodialysis access.

After establishing eligibility, subjects will be randomized in a 1:1 ratio to receive rhThrombin (1000 U/mL) or bovine thrombin (1000 U/mL). During a surgical procedure, study participants will be treated with blinded study drug (rhThrombin or bovine thrombin) in combination with an absorbable gelatin sponge at appropriate bleeding evaluation site(s) and time to hemostasis (TTH) will be assessed for up to 10 minutes. Bleeding appropriate for TTH evaluation is defined as mild to moderate bleeding, either on its own or remaining after brisk bleeding has been controlled by standard surgical modalities. Blinded study drug may also be used at additional appropriate bleeding sites. Study participants will have follow-up visits at about 2 days and 1 month after surgery. Approximately 400 to 600 patients will participate in the study. The final sample size will be determined based on blinded interim results.

• Biological: rThrombin
  1000 U/mL applied topically in combination with absorbable gelatin sponge
• Drug: bovine thrombin
  1000 U/mL applied topically in combination with absorbable gelatin sponge
  Other Name: Thrombin-JMI

• Experimental: 1
  rThrombin
  Intervention: Biological: rThrombin
• Active Comparator: 2
  bThrombin
  Intervention: Drug: bovine thrombin

• Weaver FA, Lew W, Granke K, Yonehiro L, Delange B, Alexander WA; Study Investigators. 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 Jun;47(6):1266-73. Epub 2008 Apr 28.
• Chapman WC, Singla N, Genyk Y, McNeil JW, Renkens KL Jr, Reynolds TC, Murphy A, Weaver FA. 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 Aug;205(2):256-65. Epub 2007 Jun 27.

Inclusion Criteria:

• Subject is undergoing spinal surgery, hepatic resection, peripheral arterial bypass surgery, or arteriovenous graft formation for hemodialysis access

Exclusion Criteria:

• Subject has undergone a therapeutic surgical procedure within 30 days prior to surgery
• Subject has history of heparin-induced thrombocytopenia
• Subject has known antibodies or hypersensitivity to thrombin or other coagulation factors or known sensitivity to other components of the study treatment
• Subject has received blood products within 24 hours prior to surgery