Objective: A Phase II trial to determine if nasal disinfection with 0.5% povidone-iodine (PVP-I) may be a useful adjunct in the management of COVID-19 to evaluate its potential role in future respiratory virus outbreaks. To confirm results from a human pilot study of the PVP-I nasal spray (Nasodine) by assessing repeated and frequent doses on nasal shedding of SARS-CoV-2 from adult subjects with confirmed COVID-19 Methods: A multicenter, randomised, double-blinded, placebo-controlled Phase II clinical trial was conducted during the 2022/23 season involving adult subjects with early COVID-19 symptoms. Baseline nasal swabs were collected to quantify SARS-CoV-2 pre-treatment, followed by Nasodine treatment 8 times daily over 3 calendar days. Daily nasal swabs were collected at least 30 minutes post-dose to assess the impact of treatment on nasal viable viral load. Results: Nasodine subjects exhibited significantly improved reduction in viral load (log10 TCID50) on Days 2-4 compared to Placebo recipients (p=0.028), despite substantially lower recruitment numbers compared to the target (23 in the ITTi compared to a target of 144). Subjects exhibited improved rate of clearance of viable virus (p=0.032). Viable virus was cleared (reduced to undetectable levels) from 70% of Nasodine recipients by day 3 (compared to 46% of placebo recipients) and 100% by day 4 and remained undetectable in both nasal and throat samples at day 5. Conclusion: 0.5% PVP-I nasal spray (in the form of 20 doses of Nasodine® administered over 2.5 days) significantly reduced the titers of viable SARS-CoV-2 virus in the nasal passages of COVID-19 subjects over days 2-4 compared to placebo (p=0.028). Nasodine, as a broad-spectrum topical disinfectant, may be useful in reducing viral titers and transmission risk during COVID-19 outbreaks and as a readily deployable, broad-spectrum, well tolerated, and cost-effective intervention for other outbreaks of upper respiratory tract diseases.

Aims: Hereditary Hemorrhagic Telangiectasia (HHT) is a condition marked by recurring, persistent epistaxis with significant patient morbidity. This study investigated the potential anti-angiogenic effects of oral propranolol in reducing the severity and frequency of epistaxis in patients with HHT. Methods: A double-blind randomized clinical trial, conducted from 2021-2023 at the Royal Brisbane tertiary rhinology service. Inclusion criteria were: confirmed HHT; an Epistaxis Severity Score (ESS) ≥4 despite conservative therapy. Participants were randomized into placebo (control) or a 40mg twice daily propranolol group. All patients were screened by a cardiologist at baseline. Primary outcome was ESS at 3- and 6-months, with secondary outcomes including endoscopic scoring of nasal mucosa, HHT-QoL, SF-36, and patient diaries. Results: 23 participants were enrolled, of whom 15 participants (4 placebo, 11 intervention) completed the trial. Patients randomised to receive propranolol demonstrated significantly reduced ESS scores at 3 months (mean reduction -1.71, SD 2.07, p=0.018). This reduction did not reach statistical significance compared to placebo, t(13) = -1.17, p=0.264). Reduction in endoscopic severity scores was observed in both control and propranolol groups. Dizziness (33%) and fatigue (13%) were the most common adverse events in the propranolol group, leading to withdrawal in 3 patients (and 1 placebo). A further 2 patients who received placebo withdrew before 3-months due to no perceived change in symptoms. No significant changes in blood pressure or heart rate were observed. Data for 6-month visits, patient diary, HHT-QoL and SF-36 will be available upon study completion in January 2024. Conclusion: Oral propranolol led to a reduction in epistaxis in this trial in HHT but did not reach statistical significance over placebo. Further study is indicated, with suggested close monitoring of heart rate and BP and potential dose adjustments.