A phase 3, randomized, double-blind comparative study of the efficacy and safety of topical recombinant human thrombin and bovine thrombin in surgical hemostasis.
BACKGROUND
Plasma-derived bovine thrombin is used as a topical agent to improve surgical hemostasis, but development of antibodies to bovine hemostatic proteins has been associated with increased bleeding and thrombotic complications. Recombinant human thrombin could reduce the risk of these complications.


METHODS
The objective of this randomized, double-blind, comparative trial was to compare the efficacy, safety, and antigenicity of recombinant human thrombin (rhThrombin) and bovine thrombin as adjuncts to hemostasis in liver resection, spine, peripheral arterial bypass, and dialysis access surgery. Blinded study drug was applied topically to bleeding sites with an absorbable gelatin sponge. The primary efficacy end point was time to hemostasis, summarized as the incidence of hemostasis within 10 minutes. Safety analyses were conducted for 1 month after operation, and the development of antibodies to rhThrombin or to the bovine product was evaluated.


RESULTS
Four hundred one patients completed this trial. Hemostasis was achieved at the time-to-hemostasis evaluation site within 10 minutes in 95% of patients in each treatment group. Overall complications, including operative mortality, adverse events, and laboratory abnormalities, were similar between groups. Forty-three (21.5%) patients receiving bovine thrombin developed antibodies to the product; three patients (1.5%; p < 0.0001) in the rhThrombin group developed antibodies to rhThrombin. None of the three patients who developed antirhThrombin antibodies had abnormal coagulation laboratory results or bleeding, thromboembolic, or hypersensitivity events.


CONCLUSIONS
Results of this trial suggest that rhThrombin has comparable efficacy, a similar safety profile, and is considerably less immunogenic than bovine thrombin when used for surgical hemostasis.
Department of Surgery, Section of Transplantation, Washington University, St Louis School of Medicine, St Louis, MO 63110, USA.
William C
WC
Chapman
Neil
N
Singla
Yuri
Y
Genyk
James W
JW
McNeil
Kenneth L
KL
Renkens
Thomas C
TC
Reynolds
Aileen
A
Murphy
Fred A
FA
Weaver
D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D005260:Female; D006488:Hemostasis, Surgical; D006490:Hemostatics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use*; D013917:Thrombin / Q000627:therapeutic use*
D006490:Hemostatics; D011994:Recombinant Proteins; D013917:Thrombin; C513462:recombinant human thrombin