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

[This corrects the article DOI: 10.1016/j.lansea.2022.100036.].

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 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.

Evaluation of the Safety and Efficacy of Favipiravir in Adult Indian Patients with Mild-to-Moderate COVID-19 in a Real-World Setting.

Purpose: To evaluate the safety and efficacy of favipiravir, which is prescribed for the treatment of patients with mild-to-moderate coronavirus disease 2019 (COVID-19) in India. Patients and Methods: This was a prospective, open-label, multicenter, single-arm postmarketing study conducted in India. Patients with mild-to-moderate COVID-19 received favipiravir (3600 mg [1800 mg orally twice daily] on the first day, followed by 800 mg orally twice daily, up to a maximum of 14 days) as a part of their treatment. The primary endpoints were to evaluate the safety of favipiravir by assessing the number of adverse events (AEs) and treatment-related AEs. The secondary endpoints were to evaluate the efficacy of favipiravir by assessing time to clinical cure, rate of clinical cure, time to pyrexia resolution, rate of oxygen requirement, and all-cause mortality. Results: A total of 1083 patients were enrolled in this study from December 2020 to June 2021. Adverse events were reported in 129 patients (11.9%), 116 (10.7%) of whom had mild AEs. Dose modification or withdrawal of favipiravir treatment was reported in four patients (0.37%). The median time to clinical cure and pyrexia resolution was 7 and 4 days, respectively. A total of 1036 patients (95.8%) exhibited clinical cure by day 14. Oxygen support was required by 15 patients (1.4%). One death was reported, which was unrelated to favipiravir. Conclusion: In the real-world setting, favipiravir was well-tolerated, and no new safety signals were detected.

Efficacy and safety of single-inhaler triple therapy of glycopyrronium, formoterol and fluticasone in patients with COPD: a double-blind, randomised controlled trial.

BACKGROUND: The aim of this work was to investigate the safety and efficacy of single-inhaler triple therapy with 12.5 µg glycopyrronium (GB)/12 µg formoterol fumarate (FF)/250 µg fluticasone propionate (FP), compared to 50 µg GB co-administered with a fixed dose of 12 µg FF/250 µg FP in subjects with COPD. METHODS: This was a phase 3, randomised, double-blind, active-control, parallel-group, noninferiority study conducted at 20 sites across India. COPD patients aged ≥40 to ≤75 years, with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.70, using mono/dual therapy with inhaled corticosteroids (ICSs), long-acting muscarinic antagonists (LAMAs), or long-acting ß-agonists (LABAs) for ≥1 month, were included. Subjects were randomised 1:1 to GB/FF/FP or GB+FF/FP for 12 weeks. The primary efficacy end-point was the change from baseline in trough FEV1 at the end of 12 weeks. The study is registered with the Clinical Trials Registry of India (identifier number: CTRI/2019/01/017156). RESULTS: Between 23 March 2019 and 14 February 2020, 396 subjects were enrolled, with 198 patients each in the fixed-triple (GB/FF/FP) and open-triple (GB+FF/FP) groups. The difference in least-square mean (LSM) changes in pre-dose FEV1 from baseline at 12 weeks was noninferior between the groups (p<0.05). The LSM change from baseline in post-dose FEV1 was comparable (p=0.38). A superiority test showed comparable efficacy (p=0.12) for the difference in mean change from baseline in trough FEV1 between the groups. Adverse events (mild or moderate) were recorded in 25.3% and 24.9% of subjects in the GB/FF/FP and GB+FF/FP groups. CONCLUSIONS: Fixed triple therapy with GB/FF/FP provides comparable bronchodilation and lung function improvement as open-triple therapy. It is safe and well tolerated in symptomatic COPD patients with a history of exacerbations.

Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: A randomized, comparative, open-label, multicenter, phase 3 clinical trial.

OBJECTIVE: To assess the efficacy and safety of favipiravir in adults with mild-to-moderate coronavirus disease 2019 (COVID-19). METHODS: In this randomized, open-label, parallel-arm, multicenter, phase 3 trial, adults (18-75 years) with RT-PCR confirmed COVID-19 and mild-to-moderate symptoms (including asymptomatic) were randomized 1:1 to oral favipiravir (day 1: 1800 mg BID and days 2-14: 800 mg BID) plus standard supportive care versus supportive care alone. The primary endpoint was time to the cessation of viral shedding; time to clinical cure was also measured. RESULTS: From May 14 to July 3, 2020, 150 patients were randomized to favipiravir (n = 75) or control (n = 75). Median time to the cessation of viral shedding was 5 days (95% CI: 4 days, 7 days) versus 7 days (95% CI: 5 days, 8 days), P = 0.129, and median time to clinical cure was 3 days (95% CI: 3 days, 4 days) versus 5 days (95% CI: 4 days, 6 days), P = 0.030, for favipiravir and control, respectively. Adverse events were observed in 36% of favipiravir and 8% of control patients. One control patient died due to worsening disease. CONCLUSION: The lack of statistical significance on the primary endpoint was confounded by limitations of the RT-PCR assay. Significant improvement in time to clinical cure suggests favipiravir may be beneficial in mild-to-moderate COVID-19.