Core warming of coronavirus disease 2019 (COVID-19) patients undergoing mechanical ventilation—A protocol for a randomized controlled pilot study

Background: Coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, is spreading rapidly across the globe, with little proven effective therapy. Fever is seen in most cases of COVID-19, at least at the initial stages of illness. Although fever is typically treated (with antipyretics or directly with ice or other mechanical means), increasing data suggest that fever is a protective adaptive response that facilitates recovery from infectious illness. Objective: To describe a randomized controlled pilot study of core warming patients with COVID-19 undergoing mechanical ventilation. Methods: This prospective single-site randomized controlled pilot study will enroll 20 patients undergoing mechanical ventilation for respiratory failure due to COVID-19. Patients will be randomized 1:1 to standard-of-care or to receive core warming via an esophageal heat exchanger commonly utilized in critical care and surgical patients. The primary outcome is patient viral load measured by lower respiratory tract sample. Secondary outcomes include severity of acute respiratory distress syndrome (as measured by PaO2/FiO2 ratio) 24, 48, and 72 hours after initiation of treatment, hospital and intensive care unit length of stay, duration of mechanical ventilation, and 30-day mortality. Results: Resulting data will provide effect size estimates to guide a definitive multi-center randomized clinical trial. ClinicalTrials.gov registration number: NCT04426344. Conclusions: With growing data to support clinical benefits of elevated temperature in infectious illness, this study will provide data to guide further understanding of the role of active temperature management in COVID-19 treatment and provide effect size estimates to power larger studies.