SARS-CoV-2 accelerated clearance using a novel nitric oxide nasal spray (NONS) treatment: A randomized trial

Background Additional outpatient therapies which are readily accessible will be essential to reduce COVID-19 ill-ness progression in high risk individuals. Especially as the virus continues to mutate with greater transmissibility despite increased global vaccination. Methods A randomized, double-blind, multicentre, parallel group, placebo-controlled phase III clinical trial evaluated the ability of nitric oxide (NO) to rapidly eradicate nasal SARS-CoV-2 RNA. Adults (18-70 years) with mild symptomatic COVID-19 were randomized, confirmed by laboratory SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) nasal swab. Randomisation was 1:1, NONS (N = 153) vs placebo (N = 153). NO generated by a nasal spray (NONS) was self-administered six times daily as two sprays per nostril (0.45 mL of solution/dose) for seven days. Patients at high risk of illness progression, defined as unvaccinated, >= 45 years of age or having comorbidities, were the primary analysis population.Findings Overall, mean SARS-CoV-2 RNA concentrations (6.96 log10 copies/mL in the NONS group and 7.16 log10 copies/mL in the placebo group) were comparable at baseline. Primary endpoint mean treatment difference SARS-CoV-2 RNA change from baseline to the end of treatment (EOT) was-0.52 copies/mL (SE 0.202, 95% CI-0. 92 to-0.12; p = 0.010) with NONS compared to placebo. Secondary endpoint assessments demonstrated a greater proportion of patients receiving NONS (82.8%) cleared SARS-CoV-2 (RT-PCR negative) by EOT compared to placebo (66.7%, p = 0.046), with no virus RNA detected a median of four days earlier compared to placebo (three vs seven days; p = 0.044).Interpretation Use of NONS in patients recently infected with SARS-CoV-2 accelerates nasal virus clearance.