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

Singla, Neil; Ballard, Jeffrey L.; Moneta, Gregory L.; Randleman, C. Duane; Renkens, Kenneth L.; Alexander, W. Allan

doi:10.1016/j.jamcollsurg.2009.03.016

Cited by 24 publications

(32 citation statements)

References 10 publications

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“…The immunogenicity analysis set in the current study included 9 patients who were 0 to 2 years old; their response to application of rThrombin appeared comparable with that of the 18 patients who were 3 to 17 years old, as none of the patients in either age group became antibody-positive at day 29. The lack of immunogenicity observed in this study is consistent with the low incidence of immunogenicity observed in previous studies of rThrombin in adult surgical populations [7][8][9][10][11].…”

Section: Discussionsupporting

confidence: 92%

“…For this reason, according to product labeling, patients with antibodies to bovine thrombin products should not be reexposed to those products [4]. In a previous study enrolling an adult population of patients with definite or highly likely previous exposure to bovine thrombin, 15.6% of the patients had antibodies to bovine thrombin product at study entry, before the study surgical procedure [10]. The presence of antibodies to bovine thrombin product was not evaluated in the pediatric patients included in the current study.…”

Section: Discussionmentioning

confidence: 99%

“…Eight clinical trials have shown that rThrombin is well tolerated and minimally immunogenic, and can be safely applied as an aid to hemostasis in a variety of surgical settings [7][8][9][10][11]. Trials assessing hemostatic efficacy of rThrombin included a randomized, double-blind, active comparator trial [9] and an open-label, noncomparative trial, which focused on use of rThrombin as an aid to hemostasis in burn wound excision and skin grafting in an adult and adolescent patient population [7].…”

mentioning

confidence: 99%

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Recombinant human thrombin: safety and immunogenicity in pediatric burn wound excision

Foster

Mullins

Greenhalgh

et al. 2011

Journal of Pediatric Surgery

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Recombinant human thrombin: safety and immunogenicity in pediatric burn wound excision

Foster

Mullins

Greenhalgh

et al. 2011

Journal of Pediatric Surgery

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“…The efficacy of topical thrombin at a concentration of 1000 IU/mL was recently demonstrated in clinical trials, although no clinical trials have compared the effects of different concentrations of topical thrombin on hemostatic efficacy [3-5]. The critical role of thrombin concentration in fibrin clot formation has been demonstrated in a number of in vitro settings; clots formed in the presence of higher concentrations of thrombin had more tightly packed fibrin strands and were more resistant to fibrinolysis, when compared with clots formed in the presence of lower concentrations of thrombin [6-8].…”

Section: Introductionmentioning

confidence: 99%

Topical recombinant thrombin at a concentration of 1000 IU/mL reliably shortens in vivo TTH and delivers durable hemostasis in the presence of heparin anticoagulation and clopidogrel platelet inhibition in a rabbit model of vascular bleeding

Hughes¹,

Bishop²,

García³

et al. 2009

Ann Surg Innov Res

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BackgroundThis study was designed to evaluate the effect of recombinant human thrombin (rThrombin) concentration on time to hemostasis (TTH), clot durability, and clot strength in settings that replicate the heparinization and platelet inhibition often found in surgical populations.MethodsA modified, anticoagulated rabbit arteriovenous shunt preparation was selected to model vascular anastomotic bleeding. Rabbits were treated with heparin or heparin + clopidogrel and TTH was measured after applying a range of topical rThrombin concentrations or placebo, in combination with absorbable gelatin sponge, USP. Treatments (placebo, rThrombin) were randomly assigned and the investigator was blinded to treatment. TTH was evaluated with the Kaplan-Meier method. After hemostasis was achieved, clot burst assessment was performed for heparin + clopidogrel treated animals. Clot viscoelastic strength and kinetics were measured in ex-vivo samples using thromboelastography (TEG) methods.ResultsTTH decreased with increasing concentrations of rThrombin in heparin-treated animals and was shorter after treatment with 1000 IU/mL rThrombin (73 seconds) than with 125 IU/mL rThrombin (78 seconds; p = 0.007). TTH also decreased with increasing concentrations of rThrombin in heparin + clopidogrel treated animals; again it was significantly shorter after treatment with 1000 IU/mL rThrombin (71 seconds) than with 125 IU/mL rThrombin (177 seconds; p < 0.001). Variability in TTH was significantly smaller after treatment with 1000 IU/mL rThrombin than after 125 IU/mL rThrombin, indicating greater reliability of clot formation (p < 0.001 for heparin or heparin + clopidogrel treatments). Clot durability was examined in heparin + clopidogrel treated animals. Clots formed in the presence of 1000 IU/mL rThrombin were significantly less likely to rupture during clot burst assessment than those formed in the presence of 125 IU/mL rThrombin (0% versus 79%, p < 0.001). In vitro clot strength and clot kinetics, as determined by TEG in heparin + clopidogrel samples, were positively associated with the amount of rThrombin activity added for clot initiation.ConclusionIn an animal model designed to replicate the anti-coagulation regimens encountered in clinical settings, topical rThrombin at 1000 IU/mL more reliably controlled the pharmacological effects of heparin or heparin + clopidogrel on hemostasis than rThrombin at 125 IU/mL. Results from in vitro assessments confirmed a positive relationship between the amount of rThrombin activity and both the rate of clot formation and clot strength.

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“…Other studies support the low immunogenicity of recombinant thrombin, noting that the antibodies formed did not neutralize native human thrombin [24,26]. This finding suggests that recombinant human thrombin may safely enhance hemostasis, even in patients with preexisting anti-bovine thrombin antibodies [27].…”

Section: Intraoperative Techniques To Minimize Blood Lossmentioning

confidence: 96%

Blood utilization: fostering an effective hospital transfusion culture

Sherman

MacIvor

2012

Journal of Clinical Anesthesia

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

Cited by 24 publications

References 10 publications

Recombinant human thrombin: safety and immunogenicity in pediatric burn wound excision

Recombinant human thrombin: safety and immunogenicity in pediatric burn wound excision

Topical recombinant thrombin at a concentration of 1000 IU/mL reliably shortens in vivo TTH and delivers durable hemostasis in the presence of heparin anticoagulation and clopidogrel platelet inhibition in a rabbit model of vascular bleeding

Blood utilization: fostering an effective hospital transfusion culture

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