A Phase 3b, Open-Label, Single-Group Immunogenicity and Safety Study of Topical Recombinant Thrombin in Surgical Hemostasis

Neil K. Singla, Jeffrey L. Ballard, Gregory (Greg) Moneta, C. Duane Randleman, Kenneth L. Renkens, W. Allan Alexander

    Research output: Contribution to journalArticle

    19 Citations (Scopus)

    Abstract

    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. Study Design: 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 ≥ 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.

    Original languageEnglish (US)
    Pages (from-to)68-74
    Number of pages7
    JournalJournal of the American College of Surgeons
    Volume209
    Issue number1
    DOIs
    StatePublished - Jul 2009

    Fingerprint

    Surgical Hemostasis
    Thrombin
    Safety
    Antibodies
    Blood Vessels
    Hemostasis

    ASJC Scopus subject areas

    • Surgery

    Cite this

    A Phase 3b, Open-Label, Single-Group Immunogenicity and Safety Study of Topical Recombinant Thrombin in Surgical Hemostasis. / Singla, Neil K.; Ballard, Jeffrey L.; Moneta, Gregory (Greg); Randleman, C. Duane; Renkens, Kenneth L.; Alexander, W. Allan.

    In: Journal of the American College of Surgeons, Vol. 209, No. 1, 07.2009, p. 68-74.

    Research output: Contribution to journalArticle

    Singla, Neil K. ; Ballard, Jeffrey L. ; Moneta, Gregory (Greg) ; Randleman, C. Duane ; Renkens, Kenneth L. ; Alexander, W. Allan. / A Phase 3b, Open-Label, Single-Group Immunogenicity and Safety Study of Topical Recombinant Thrombin in Surgical Hemostasis. In: Journal of the American College of Surgeons. 2009 ; Vol. 209, No. 1. pp. 68-74.
    @article{154c9d71d00e4711b8a64039f4f0e113,
    title = "A Phase 3b, Open-Label, Single-Group Immunogenicity and Safety Study of Topical Recombinant Thrombin in Surgical Hemostasis",
    abstract = "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. Study Design: 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 ≥ 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.",
    author = "Singla, {Neil K.} and Ballard, {Jeffrey L.} and Moneta, {Gregory (Greg)} and Randleman, {C. Duane} and Renkens, {Kenneth L.} and Alexander, {W. Allan}",
    year = "2009",
    month = "7",
    doi = "10.1016/j.jamcollsurg.2009.03.016",
    language = "English (US)",
    volume = "209",
    pages = "68--74",
    journal = "Journal of the American College of Surgeons",
    issn = "1072-7515",
    publisher = "Elsevier Inc.",
    number = "1",

    }

    TY - JOUR

    T1 - A Phase 3b, Open-Label, Single-Group Immunogenicity and Safety Study of Topical Recombinant Thrombin in Surgical Hemostasis

    AU - Singla, Neil K.

    AU - Ballard, Jeffrey L.

    AU - Moneta, Gregory (Greg)

    AU - Randleman, C. Duane

    AU - Renkens, Kenneth L.

    AU - Alexander, W. Allan

    PY - 2009/7

    Y1 - 2009/7

    N2 - 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. Study Design: 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 ≥ 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.

    AB - 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. Study Design: 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 ≥ 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.

    UR - http://www.scopus.com/inward/record.url?scp=67549111906&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=67549111906&partnerID=8YFLogxK

    U2 - 10.1016/j.jamcollsurg.2009.03.016

    DO - 10.1016/j.jamcollsurg.2009.03.016

    M3 - Article

    C2 - 19651065

    AN - SCOPUS:67549111906

    VL - 209

    SP - 68

    EP - 74

    JO - Journal of the American College of Surgeons

    JF - Journal of the American College of Surgeons

    SN - 1072-7515

    IS - 1

    ER -