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

Abstract

Background: Additional outpatient therapies which are readily accessible will be essential to reduce COVID-19 illness 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.

Funding: Funding provided by Glenmark Pharmaceuticals Limited. Study medication provided by SaNOtize.

Keywords: Anti-viral treatment; COVID-19; Nasal Spray; SARS-CoV-2; Viral load.

Figure 1

NONS Study Trial Disposition.

Figure 2

Kaplan–Meier curve for time to negative conversion of SARS-CoV 2 RT PCR (mITT high risk population).

Figure 3

Proportion of adult COVID-19 infected patients with ≥2 point clinical status improvement in WHO progression scale score (mITT high risk population).

Figure 4

Trial patients’ immediate contacts reporting testing COVID-19 positive and immediate contacts having COVID-19 symptoms (mITT high risk population).

Figure 5

Methemoglobin levels with NONS treatment at each visit day in adult COVID-19 patients.