Phase 3, randomized, double-blind study of plasma-derived human thrombin versus bovine thrombin in achieving hemostasis in patients undergoing surgery

Curr Med Res Opin. 2008 Mar;24(3):785-94. doi: 10.1185/030079908X273426. Epub 2008 Jan 31.

Abstract

Objective: To compare the effectiveness of plasma-derived human thrombin and bovine thrombin for achieving hemostasis during surgery.

Methods: Adults (N = 305) with > or = 1 mild or moderate bleeding site not manageable by conventional modalities during elective cardiovascular, neurologic, or general surgical procedures at multiple study centers were randomized to human (n = 153) or bovine (n = 152) thrombin, applied topically with an absorbable gelatin sponge. Bleeding was assessed 3, 6, and 10 min post-application. Other evaluations included laboratory assessments, vital signs, blood loss, blood transfusions, time in specialty-care units, procedure duration, and length of hospital stay. Blood samples for antibody assessment were collected at baseline and postoperative week 5.

Results: The proportion of patients achieving hemostasis within 10 min (primary outcome) was equivalent for human and bovine thrombin (97.4 vs. 97.4%, respectively; ratio, 1.00; 95% CI, 0.96-1.05). The proportions of patients achieving hemostasis at 6 min (94.8 vs. 92.8%) and 3 min (73.2 vs. 72.4%) were also equivalent. No clinically meaningful differences were noted for other variables. The products had similar adverse event profiles. More patients (12.7%) who received bovine thrombin demonstrated seroconversion for > or = 1 of the 4 antibodies assayed than patients who received human thrombin (3.3%). No patients in the human thrombin group developed seroconversion for anti-human thrombin or anti-human factor V/Va antibodies. Limitations of this study include the lack of a placebo-control group, the potential for inter-surgeon variability, and the fact that antibody assessment was not evaluable in all patients.

Conclusions: Plasma-derived human thrombin and bovine thrombin were equivalent in achieving hemostasis within 10, 6, and 3 min and had comparable safety profiles. None of the patients receiving human thrombin developed seroconversion for antibodies to any of the human antigens.

Trial registration: ClinicalTrials.gov NCT00196534.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Loss, Surgical / prevention & control*
  • Cardiovascular Surgical Procedures / methods*
  • Cattle
  • Double-Blind Method
  • Female
  • Hemostasis, Surgical*
  • Hemostatics / blood*
  • Humans
  • Intraoperative Complications / prevention & control
  • Length of Stay
  • Male
  • Middle Aged
  • Neurosurgical Procedures*
  • Perioperative Care
  • Postoperative Hemorrhage / prevention & control*
  • Prospective Studies
  • Thrombin / therapeutic use*
  • Thrombin Time

Substances

  • Hemostatics
  • Thrombin

Associated data

  • ClinicalTrials.gov/NCT00196534