A phase 3b, open-label, single-group immunogenicity and safety study of topical recombinant thrombin in surgical hemostasis.
BACKGROUND
The immunogenicity and safety of recombinant human thrombin (rThrombin) were evaluated in this phase 3b, open-label, single-group, multisite study of 209 adult vascular and spinal operation patients at high risk for preexisting anti-bovine thrombin product antibodies.


METHODS
Patients received rThrombin applied as a topical hemostat during a surgical procedure (day 1). Immunogenicity samples were collected at baseline and approximately 1 month after operation (day 29) and were analyzed after study participation.


RESULTS
Mean patient age was 61.5 years; median number of previous surgical procedures was 5.0 (range, 1 to 25). Operation types included spinal (n = 89 of 209 [43%]), arterial reconstruction (including peripheral arterial bypass; n = 75 of 209 [36%]), and arteriovenous vascular access procedures (n = 45 of 209 [22%]). All patients had confirmed or highly likely previous bovine thrombin exposure; at baseline, 15.6% of patients (n = 32 of 205) had preexisting anti-bovine thrombin antibodies. Of 200 patients with complete immunogenicity evaluations, 31 had preexisting anti-bovine thrombin antibodies (15.5%), and 4 had preexisting anti-rThrombin product antibodies (2.0%). None of the 200 patients became antibody positive for rThrombin antibodies on day 29 (seroconversion or > or = 10-fold increase in titer). Adverse events and laboratory results were consistent with a surgical population with substantial comorbidities. Patients with preexisting antibodies to bovine thrombin were older (p = 0.04) and had undergone more surgical procedures previously (p < 0.001) than patients without preexisting antibodies.


CONCLUSIONS
Results of this study confirm the low immunogenicity of rThrombin and suggest that rThrombin can be used safely as an aid to hemostasis in patients with or without preexisting anti-bovine thrombin antibodies. A sizeable proportion of this vascular and spinal operation patient population (15.6%) had preexisting anti-bovine thrombin antibodies; these patients are at risk for immune responses after reexposure to bovine thrombin.
Singla
Neil K
NK
Lotus Clinical Research, Huntington Memorial Hospital, Pasadena, CA, USA.
Ballard
Jeffrey L
JL
Moneta
Gregory
G
Randleman
C Duane
CD
Renkens
Kenneth L
KL
Alexander
W Allan
WA
D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D002417:Cattle; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006488:Hemostasis, Surgical / Q000379:methods*; D006490:Hemostatics / Q000008:administration & dosage* / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000276:immunology*; D013122:Spinal Diseases / Q000601:surgery*; D013917:Thrombin / Q000008:administration & dosage* / Q000276:immunology*; D016896:Treatment Outcome; D014656:Vascular Surgical Procedures
D006490:Hemostatics; D011994:Recombinant Proteins; D013917:Thrombin; C513462:recombinant human thrombin