Recombinant thrombin: safety and immunogenicity in burn wound excision and grafting

J Burn Care Res. May-Jun 2009;30(3):371-9. doi: 10.1097/BCR.0b013e3181a28979.

Abstract

This study evaluated the safety, immunogenicity, and hemostatic effect of recombinant human Thrombin (rThrombin), in patients undergoing skin grafting for burns. This was a phase 2 multiple site, single-arm, open-label study in patients receiving partial- or full-thickness autologous grafts. rThrombin was applied using a spray applicator to newly excised wounds of 1 to 4% body surface area at 5 minutes intervals for up to 20 minutes, after point source bleeding was stopped. Adverse events, skin graft survival, and formation of anti-rThrombin antibodies were measured at baseline and Day 29. There were no deaths or study drug discontinuations. Adverse events occurred in 63 of 72 patients (88%), and were typical of sequelae of skin grafting. Hemostasis was achieved within 20 minutes after application of rThrombin in 65 of 71 patients (91.5%). Skin graft failure occurred in 4 patients (6%). At the day 29 evaluation, for those patients who returned, 88.9% had > or =90% graft survival. One patient (1 of 70, 1.4%) had specific, low titer antibodies to rThrombin at baseline, but no increase in titer posttreatment; a second patient (1 of 62, 1.6%), developed antibodies to rThrombin at day 29. None of the antibodies neutralized native human thrombin. In excised burn wounds, hemostasis at 20 minutes was achieved in 91.5% of patients and skin graft survival was excellent. There was a low rate of antibodies to rThrombin at baseline (1.4%) and a low rate of anti-rThrombin antibody formation at day 29 (1.6%). rThrombin was well tolerated when administered with a pump spray.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Adolescent
  • Adult
  • Aged
  • Burns / therapy*
  • Child
  • Female
  • Graft Survival
  • Hemostatics / administration & dosage
  • Hemostatics / immunology
  • Hemostatics / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / immunology
  • Recombinant Proteins / therapeutic use*
  • Safety
  • Skin Transplantation* / adverse effects
  • Thrombin / administration & dosage
  • Thrombin / immunology
  • Thrombin / therapeutic use*
  • Treatment Outcome
  • Wound Healing / physiology

Substances

  • Hemostatics
  • Recombinant Proteins
  • Thrombin
  • recombinant human thrombin