title: Immunogenicity and safety of re-exposure to recombinant human thrombin in surgical hemostasis.
abstract: BACKGROUND
  This Phase 4, open-label study evaluated the immunogenicity and safety of a second exposure to recombinant human thrombin (rThrombin) in adult patients with previous exposure to rThrombin.
  
  
  METHODS
  Topical rThrombin was applied as a hemostatic aid during a surgical procedure (day 1). Adverse events and clinical laboratory abnormalities were monitored to day 29 (study end). Immunogenicity samples were collected on days 1 and 29. Thirty-one patients were treated at 9 study sites; 30 patients completed the study.
  
  
  RESULTS
  Mean age was 59.5 years; 61.3% of patients were male. Study operations types included spinal (n = 23 of 31; 74.2%), arterial reconstruction or peripheral arterial bypass (n = 4; 12.9%), arteriovenous vascular access procedure (n = 3; 9.7%), and other (n = 1; 3.2%). A median of 10 mL rThrombin (1,000 IU/mL; range 5 to 60 mL) was prepared per patient. Median elapsed time since previous rThrombin exposure was 1.3 years (range 19 days to 3.3 years). Recombinant human thrombin was not observed to be immunogenic; no patients (n = 0 of 30, 0%; 95% CI 0.0%, 11.6%) became positive for anti-rThrombin product antibodies at day 29, approximately 1 month after the second exposure to rThrombin. The most commonly reported adverse events were procedural pain (n = 23 of 31, 74.2%), constipation (n = 8, 25.8%), and nausea (n = 8, 25.8%) All adverse events and clinical laboratory abnormalities were considered unrelated to treatment. For the majority of patients, maximal severity of any adverse event was mild or moderate.
  
  
  CONCLUSIONS
  The immunogenicity and safety results of this Phase 4 rThrombin trial suggest that patients with known previous exposure may be safely re-exposed to topical rThrombin.
authors.affiliation: Lotus Clinical Research, Pasadena CA, USA.
authors.forename: Neil K
authors.initials: NK
authors.lastname: Singla
authors.forename: Antonios P
authors.initials: AP
authors.lastname: Gasparis
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Ballard
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Baron
authors.forename: Michael D
authors.initials: MD
authors.lastname: Butine
authors.forename: John P
authors.initials: JP
authors.lastname: Pribble
authors.forename: W Allan
authors.initials: WA
authors.lastname: Alexander
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000097:blood; D015331:Cohort Studies; D004334:Drug Administration Schedule; 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*; D019233:Retreatment; D013917:Thrombin / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D013997:Time Factors; D055815:Young Adult
chemical_list: D000906:Antibodies; D006490:Hemostatics; D011994:Recombinant Proteins; D013917:Thrombin; C513462:recombinant human thrombin