The Efficacy of Nitric Oxide Generating Lozenges on Outcome in Newly Diagnosed COVID-19 Patients of African American and Hispanic Origin: A Randomized Clinical Trial

BACKGROUND: The study was initiated in 2020 to test the efficacy of a nitric oxide generating lozenge (NOL) in outpatients with newly diagnosed COVID-19 to mitigate disease severity. The study enrolled high risk patients, African American and Latino. METHODS: This was a randomized, double blinded, prospective, placebo controlled trial. The primary endpoint was hospitalization, ICU admission, intubation, dialysis and death. The secondary endpoints were time to symptom resolution and the effect on oxygen saturation. Patients ages 50-85 with recent COVID-19 diagnosis with at least one risk factor were recruited. Patients were randomized either to active treatment or placebo using block randomization. Blood pressure and oxygen saturation (SpO2) was measured before and after the first dose and each AM thereafter. RESULTS: A total 840 patients was planned, half in the lozenge and placebo groups. An interim review of data was pre-specified. After 524 patients the composite endpoint occurred in 6 patients, 3 (1.1%) in each group. The time to symptom resolution was one day shorter on active treatment (8.7±6.6 versus 9.8±6.8 days) (p=0.3). There was no change in SpO2 on placebo (0.0±2.0%) and no significant change on treatment (0.14±0.9%), p=0.3. All events occurred in the first year (2020). CONCLUSIONS: This study did not find a benefit of NOL therapy in COVID-19 patients and was terminated for futility. NOL treatment did not reduce mortality, hospitalization, intubation or a reduction in symptoms duration. The study did find the NO lozenges were well tolerated in high risk patients without reported side effects.