Phase 3, randomized, double-blind study of plasma-derived human thrombin versus bovine thrombin in achieving hemostasis in patients undergoing surgery.
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.
Doria
Cataldo
C
Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA. cataldo.doria@jefferson.edu
Fischer
Craig P
CP
Wood
Christopher G
CG
Li
P Mark
PM
Marra
Steven
S
Hart
James
J
D000818:Animals; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D013504:Cardiovascular Surgical Procedures / Q000379:methods*; D002417:Cattle; D004311:Double-Blind Method; D005260:Female; D006488:Hemostasis, Surgical; D006490:Hemostatics / Q000097:blood*; D006801:Humans; D007431:Intraoperative Complications / Q000517:prevention & control; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D019635:Neurosurgical Procedures; D019990:Perioperative Care; D019106:Postoperative Hemorrhage / Q000517:prevention & control*; D011446:Prospective Studies; D013917:Thrombin / Q000627:therapeutic use*; D013918:Thrombin Time
D006490:Hemostatics; D013917:Thrombin