Efficacy of BREATHOX? Device Inhalation on Acute Symptoms Associated with COVID-19 (BREATH Study): A Randomized Pilot Clinical Trial

(1) Background: A high concentration of sodium chloride on in vitro cell culture leads to reduced SARS-CoV-2 replication. Therefore, our aim was to evaluate the effects of inhaling hypertonic NaCl particles (BREATHOX (R)) on the duration of COVID-19-induced acute symptoms. (2) Methods: A prospective, open label, randomized, standard of care-controlled group (SOC) pilot trial compared inhaled oral and nasal administered BREATHOX (R) (2.0 mg NaCl, particles size between 1-10 mu m), with five or ten inhalations per day for ten days. The primary endpoint was the time to resolve COVID-19-related symptoms. Safety outcomes included adverse clinical and laboratory events. (3) Results: A total of 101 individuals were screened and 98 were randomly assigned to BREATHOX (R) ten sessions per day (Group 1; 33 patients), BREATHOX (R) five sessions per day (Group 2; 32 patients), or SOC (33 patients), and followed up for 28 days. There was an association with cough frequency after 10 days BREATHOX (R) compared to SOC [Group 1: hazard ratio (HR) 2.01, 95% confidence interval (CI) 1.06-3.81; Group 2: HR 2.17, 95% CI 1.17-4.04]. No differences between the groups for the reported symptoms' resolution time were seen after 28 days. After combining both BREATHOX (R) groups, the period to cough resolution 10 days after randomization was significantly lower than in SOC (HR 2.10, 95% CI 1.20-3.67). An adverse event occurred in 30% of Group 1, 36% of Group 2, and 9% in SOC individuals. One patient from SOC had a serious adverse event. Nasal burning, sore or itchy nose, and dry mouth were considered related to BREATHOX (R) use and resolved after stopping inhalations. (4) Conclusion: BREATHOX (R) inhalation is safe and may be effective in reducing the duration of COVID-19-induced coughing.