title: Safety and immunogenicity observations pooled from eight clinical trials of recombinant human thrombin.
abstract: BACKGROUND
  We evaluated safety and immunogenicity observations pooled from 8 clinical trials of recombinant human thrombin (rThrombin), an active topical hemostatic agent.
  
  
  METHODS
  Recombinant thrombin was applied with an absorbable gelatin sponge or spray applicator during a surgical procedure (day 1). Adverse events and laboratory parameters were monitored until study end (day 29). Immunogenicity was evaluated after study completion on plasma samples collected at baseline and on day 29.
  
  
  RESULTS
  Studies included 583 rThrombin-treated patients (median age, 59 years; 54% men). Surgical procedures included: spinal, 33% of patients; hepatic resection, 14%; peripheral arterial bypass, 23%; arteriovenous graft formation for hemodialysis access, 18%; and skin graft after burn wound excision, 12%. Adverse events reported for >or= 10% patients included incision site pain, procedural pain, nausea, constipation, pyrexia, anemia, insomnia, vomiting, and pruritus. Five of 552 patients developed antibodies to rThrombin (0.9%; 95% CI, 0.3 to 2.1; day 29); antibodies did not neutralize the biologic activity of native human thrombin. At baseline, 12 patients had pre-existing, antibodies recognizing rThrombin (12 of 552; 2.2%; 95% CI, 1.1 to 3.8); these patients had no previous exposure to rThrombin and their antibody titer did not increase >or= 1.0 unit (>or= 10-fold) at day 29.
  
  
  CONCLUSIONS
  Results from 8 clinical trials collectively demonstrated that rThrombin is well tolerated in numerous surgical settings when used as a topical adjunct to hemostasis. Adverse events and changes in laboratory parameters were consistent with commonly reported postoperative events. Less than 1% of patients developed antibodies to rThrombin; the antibodies did not neutralize native human thrombin.
authors.affiliation: Vascular and Interventional Specialists of Orange County, Inc, Orange, CA, USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Ballard
authors.forename: Fred A
authors.initials: FA
authors.lastname: Weaver
authors.forename: Neil K
authors.initials: NK
authors.lastname: Singla
authors.forename: William C
authors.initials: WC
authors.lastname: Chapman
authors.forename: W Allan
authors.initials: WA
authors.lastname: Alexander
mesh_terms: D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000097:blood; D002648:Child; D002986:Clinical Trials as Topic; D005260:Female; D006488:Hemostasis, Surgical; D006490:Hemostatics / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D013917:Thrombin / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*
chemical_list: D000906:Antibodies; D006490:Hemostatics; D011994:Recombinant Proteins; D013917:Thrombin; C513462:recombinant human thrombin