Long-term randomized controlled trial of a novel nanopowder hemostatic agent (TC-325) for control of severe arterial upper gastrointestinal bleeding in a porcine model

Abstract

Background and study aim: Endoscopic therapy of brisk upper gastrointestinal bleeding remains challenging. A proprietary nanopowder (TC-325) has been proven to be effective in high pressure bleeding from external wounds. The efficacy and safety of TC-325 were assessed in a survival gastrointestinal bleeding animal model. Method: 10 animals were randomized to treatment or sham. All animals received intravenous antibiotics, H2-blockers and heparin (activated clotting time 2 x normal). In a sterile laparotomy the gastroepiploic vessels were dissected, inserted through a 1-cm gastrotomy, and freely exposed in the gastric lumen, and the exposed vessel lacerated by needle knife. The treatment group received TC-325 by a modified delivery catheter while the sham group received no endoscopic treatment. Time to hemostasis, and mortality at 60 minutes, 24 hours, 48 hours, and 7 days were noted. Necropsy was performed in all animals. Results: Spurting arterial bleeding was achieved in all animals. No control animal showed hemostasis within the first hour compared with 100% (5/5) in the treatment arm (mean 13.8 minutes, P < 0.0079). Durable hemostasis was achieved with no evidence of rebleeding after 1 and 24 hours in 80% (4/5) of the treated animals compared with none in the control group (P < 0.0098). None of the control animals survived more than 6 hours. Necropsy at 1 week in treated animals revealed healed gastrotomy without foreign body granuloma or embolization to the lung or brain. Conclusion: TC-325 is safe and highly effective in achieving hemostasis in an anticoagulated severe arterial gastrointestinal bleeding animal model.