Povidone-iodine nasal spray (Nasodine®) for the common cold: a randomized, controlled, double-blind, Phase III clinical trial

DOI record: { "DOI": "10.3389/fmed.2025.1565069", "ISSN": [ "2296-858X" ], "URL": "http://dx.doi.org/10.3389/fmed.2025.1565069", "abstract": "<jats:sec><jats:title>Aim</jats:title><jats:p>To determine the safety and efficacy of a 0.5% povidone-iodine nasal spray (Nasodine) as a treatment for the common cold (ACTRN12619000764134).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A multi-center, randomized, controlled, double-blind Phase III study was conducted to assess the impact of Nasodine on the common cold. Two hundred and sixty (260) euthyroid adults with qualifying cold symptoms and meeting inclusion/exclusion criteria were randomized 2:1 to Nasodine or matching saline nasal spray (SNS), each applied 4 times daily for 5 days. Cold severity was reported using the WURSS-21 survey. The primary endpoint was impact on nasal symptoms (4-item scale), with the validated 19-item Global Severity Score (GSS) as the key secondary endpoint.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>All cold severity outcomes pointed in favor of Nasodine over SNS. In the ITT (<jats:italic>n</jats:italic> = 260), the Nasodine benefit over SNS on nasal symptoms was 8.4% (<jats:italic>p</jats:italic> = 0.217). For GSS, the benefit was 12.6% (<jats:italic>p</jats:italic> = 0.054) in the ITT population. <jats:italic>Post hoc</jats:italic> subset analyses showed markedly improved benefits of Nasodine: In subjects with stronger symptoms at enrollment (ES), the GSS benefit was 17.1% (<jats:italic>p</jats:italic> = 0.023); for those with confirmed viral infection (VES), GSS benefit was 23.0% (<jats:italic>p</jats:italic> = 0.048); and for those enrolled within 24 h of symptom onset (24S), GSS benefit was 39.7% (<jats:italic>p</jats:italic> = 0.024). In terms of functional impairment, the Nasodine benefit was greater in all subsets, with 16.1% (<jats:italic>p</jats:italic> = 0.041) benefit in ITT, 22.2% in ES (<jats:italic>p</jats:italic> = 0.012), 32.1% in VES (<jats:italic>p</jats:italic> = 0.023) and 37.1% in 24S (<jats:italic>p</jats:italic> = 0.093). Nasodine was well tolerated, with mild transient nasopharyngeal discomfort being a common adverse effect.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Nasodine treatment had a consistently positive and clinically meaningful benefit on overall cold severity when compared with saline nasal spray. Early treatment after symptom onset is an important efficacy factor.</jats:p></jats:sec><jats:sec><jats:title>Clinical trial registration</jats:title><jats:p><jats:uri>https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377353&amp;amp;isReview=true</jats:uri>, identifier ACTRN12619000764134.</jats:p></jats:sec>", "alternative-id": [ "10.3389/fmed.2025.1565069" ], "author": [ { "affiliation": [], "family": "Polasek", "given": "Thomas M.", "sequence": "first" }, { "affiliation": [], "family": "Friedland", "given": "Peter L.", "sequence": "additional" } ], "container-title": "Frontiers in Medicine", "container-title-short": "Front. Med.", "content-domain": { "crossmark-restriction": true, "domain": [ "frontiersin.org" ] }, "created": { "date-parts": [ [ 2025, 6, 5 ] ], "date-time": "2025-06-05T04:10:28Z", "timestamp": 1749096628000 }, "deposited": { "date-parts": [ [ 2025, 6, 5 ] ], "date-time": "2025-06-05T04:10:29Z", "timestamp": 1749096629000 }, "indexed": { "date-parts": [ [ 2025, 6, 6 ] ], "date-time": "2025-06-06T04:02:31Z", "timestamp": 1749182551189, "version": "3.41.0" }, "is-referenced-by-count": 0, "issued": { "date-parts": [ [ 2025, 6, 5 ] ] }, "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2025, 6, 5 ] ], "date-time": "2025-06-05T00:00:00Z", "timestamp": 1749081600000 } } ], "link": [ { "URL": "https://www.frontiersin.org/articles/10.3389/fmed.2025.1565069/full", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "1965", "original-title": 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