TranExamic Atomized for Pediatric post-Operative Tonsillectomy hemorrhage (TEAPOT)

PROJECT SUMMARY/ABSTRACT Tonsillectomy is the second most common pediatric surgical procedure in the United States, with more than 530,000 performed annually. Regrettably, 4-5% of these children experience a post-tonsillectomy hemorrhage (PTH) leading to emergency departments (ED) visits, hospital readmissions, blood transfusions, and surgical interventions. Conventional interventions are limited, as the bleeding is often difficult to visualize and access, making direct pressure or medication application impractical. Currently, more than 60% of otolaryngologists (ENTs) choose a second surgery for examination under general anesthesia and cauterization to control PTH bleeding. A second surgical intervention increases morbidity due to local trauma from securing a bleeding airway, anesthesia medications that may have neurotoxic effects, and additional pain resulting from the repeat cauterization of the tonsillar bed. Our preliminary data demonstrated that three doses of nebulized tranexamic acid (TXA) delivered to children with PTH reduces the need for a second operation by 44% with no safety concerns. Compared to earlier reports and studies, nebulized TXA is the first non-operative intervention that successfully decreased the need for an invasive procedure to control upper airway bleeding in children with PTH. We also found that jet nebulized TXA at 15 L/min delivers appropriately sized particles to mostly deposit at the tonsil bed. Our overall hypothesis is that nebulized TXA is a safe and easily administered treatment decreasing the severity of bleeding and the need for repeat surgical intervention in children with PTH. In preparation for a phase 3 trial, we will build on our preliminary data and investigational new drug (IND) approval to conduct a multicenter, randomized controlled, blinded pilot trial. The objectives of the pilot trial will be to assess enrollment feasibility, protocol adherence, and TXA absorption. Our research is highly significant, offering a novel and scientifically promising intervention for a condition with substantial morbidity and a lack of effective bedside treatments. Our approach innovative, as nebulized TXA has not been well studied in children, and we will develop a pulmonary pharmacokinetic model for TXA that can be extrapolated to other bleeding conditions. The anticipated impact of this pilot study is to generate feasibility and pharmacokinetic data, setting the stage for a subsequent multicenter phase 3 clinical trial that will have the power to demonstrate the efficacy of nebulized TXA in reducing the need for surgical interventions.