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. STUDY DESIGN: 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.
BACKGROUND: This Phase 4, open-label study evaluated the immunogenicity and safety of a second exposure to recombinant humanthrombin (rThrombin) in adult patients with previous exposure to rThrombin. STUDY DESIGN: 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 humanthrombin 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.