The DAWN antivirals trial: process evaluation of a COVID-19 trial in general practice

Tare et al., BJGP Open, doi:10.3399/bjgpo.2023.0109, DAWN, NCT04730206, Nov 2023
Recovery, day 30 33% improvement lower risk ← → higher risk Recovery, day 8 23% Recovery time 25% no CI Camostat for COVID-19  DAWN  EARLY TREATMENT RCT Is early treatment with camostat beneficial for COVID-19? Double-blind RCT 36 patients in Belgium Trial underpowered to detect differences c19early.org Tare et al., BJGP Open, November 2023 0 0.5 1 1.5 2+ RR
Small early terminated RCT showing better recovery with camostat treatment, without statistical significance.
Study covers TMPRSS2 inhibitors, camostat, and molnupiravir.
risk of no recovery, 32.6% lower, RR 0.67, p = 0.70, treatment 4 of 19 (21.1%), control 5 of 16 (31.2%), NNT 9.8, day 30.
risk of no recovery, 22.8% lower, RR 0.77, p = 0.48, treatment 11 of 19 (57.9%), control 12 of 16 (75.0%), NNT 5.8, day 8.
recovery time, 25.0% lower, relative time 0.75, treatment 19, control 17.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Tare et al., 20 Nov 2023, Double Blind Randomized Controlled Trial, placebo-controlled, Belgium, peer-reviewed, median age 55.0, 11 authors, trial NCT04730206 (history) (DAWN). Contact: ann.vandenbruel@kuleuven.be.
$0 $500 $1,000+ Efficacy vs. cost for COVID-19 treatment protocols c19early.org November 2025 Belgium United Kingdom Russia USA Sudan Angola Colombia Kenya Mozambique Vietnam Peru Philippines China Uzbekistan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Bosnia-Herzegovina Ukraine Côte d'Ivoire Bulgaria Greece Slovakia Singapore Iceland New Zealand Czechia Mongolia Israel Trinidad and Tobago Hong Kong North Macedonia Belarus Qatar Panama Serbia CAR Belgium favored high-profit treatments.The average efficacy of treatments was very low.High-cost protocols reduce early treatment, andforgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
$0 $500 $1,000+ Efficacy vs. cost for COVID-19treatment protocols worldwide c19early.org November 2025 Belgium United Kingdom Russia USA Sudan Angola Colombia Kenya Mozambique Vietnam Peru Philippines China Uzbekistan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Zambia Fiji Bosnia-Herzegovina Ukraine Côte d'Ivoire Eritrea Bulgaria Greece Slovakia Singapore New Zealand Malawi Czechia Mongolia Israel Trinidad and Tobago North Macedonia Belarus Qatar Panama Serbia Syria Belgium favored high-profit treatments.The average efficacy was very low.High-cost protocols reduce early treatment,and forgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
DOI record: { "DOI": "10.3399/bjgpo.2023.0109", "ISSN": [ "2398-3795" ], "URL": "http://dx.doi.org/10.3399/bjgpo.2023.0109", "abstract": "<jats:sec><jats:title>Background</jats:title><jats:p>The DAWN Antivirals trial was a multicentric, randomised placebo-controlled trial evaluating antiviral medication for COVID-19 in general practice. The trial was prematurely terminated because of insufficient recruitment.</jats:p></jats:sec><jats:sec><jats:title>Aim</jats:title><jats:p>To explore which factors contributed to the premature termination.</jats:p></jats:sec><jats:sec><jats:title>Design &amp; setting</jats:title><jats:p>General practice in Belgium.</jats:p></jats:sec><jats:sec><jats:title>Method</jats:title><jats:p>Patients were randomized to camostat or placebo (blinded) between June 2021 and July 2022); a third arm evaluating molnupiravir (open label) was opened in March 2022. We analysed available trial data and evaluated trial context, implementation and mechanisms of impact based on semi-structured interviews with trial stakeholders.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The trial recruited 44 participants; 19 were allocated to camostat (median age 55 years), 8 to molnupiravir (median age 60 years) and 17 to placebo (median age 56 years). There were no serious adverse events in either group. Most difficulties were related to the pandemic context: disruption to routine clinical services; multiple changes to the service model for COVID-19 patients; overwhelmed clinical staff; delays of trial medication; staff shortages in the sponsor and clinical team. In addition, regulatory approval processes were lengthy and led to additional study procedures. It was felt that the trial started too late, when vaccinations had already begun.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The DAWN Antivirals trial was stopped prematurely. Although many barriers were related to the pandemic itself, hurdles such as small and inexperienced sponsor and clinical teams, delays in regulatory processes and research capacity in routine settings could be overcome by established research infrastructure and standardization of processes.</jats:p></jats:sec>", "alternative-id": [ "10.3399/BJGPO.2023.0109" ], "author": [ { "affiliation": [], "family": "Tare", "given": "Dajana", "sequence": "first" }, { "ORCID": "http://orcid.org/0000-0002-1238-8052", "affiliation": [], "authenticated-orcid": false, "family": "Coenen", "given": "Samuel", "sequence": "additional" }, { "affiliation": [], "family": "De Sutter", "given": "An", "sequence": "additional" }, { "affiliation": [], "family": "Heytens", "given": "Stefan", "sequence": "additional" }, { "affiliation": [], "family": "Devroey", "given": "Dirk", "sequence": "additional" }, { "affiliation": [], "family": "Buret", "given": "Laetitia", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0003-1909-9613", "affiliation": [], "authenticated-orcid": false, "family": "Schoenmakers", "given": "Birgitte", "sequence": "additional" }, { "affiliation": [], "family": "Delvaux", "given": "Nicolas", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-7166-7211", "affiliation": [], "authenticated-orcid": false, "family": "Verbakel", "given": "Jan Y", "sequence": "additional" }, { "affiliation": [], "family": "Bogaerts", "given": "Kris", "sequence": "additional" }, { "affiliation": [], "family": "van den Bruel", "given": "Ann", "sequence": "additional" } ], "container-title": "BJGP Open", "container-title-short": "BJGP Open", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2023, 11, 20 ] ], "date-time": "2023-11-20T13:40:11Z", "timestamp": 1700487611000 }, "deposited": { "date-parts": [ [ 2023, 11, 20 ] ], "date-time": "2023-11-20T13:40:11Z", "timestamp": 1700487611000 }, "indexed": { "date-parts": [ [ 2023, 11, 21 ] ], "date-time": "2023-11-21T00:14:19Z", "timestamp": 1700525659799 }, "is-referenced-by-count": 0, "issued": { "date-parts": [ [ 2023, 11, 20 ] ] }, "language": "en", "link": [ { "URL": "https://syndication.highwire.org/content/doi/10.3399/BJGPO.2023.0109", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "1987", "original-title": [], "page": "BJGPO.2023.0109", "prefix": "10.3399", "published": { "date-parts": [ [ 2023, 11, 20 ] ] }, "published-online": { "date-parts": [ [ 2023, 11, 20 ] ] }, "publisher": "Royal College of General Practitioners", "reference-count": 0, "references-count": 0, "relation": {}, "resource": { "primary": { "URL": "http://bjgpopen.org/lookup/doi/10.3399/BJGPO.2023.0109" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [ "Family Practice" ], "subtitle": [], "title": "The DAWN antivirals trial: process evaluation of a COVID-19 trial in general practice", "type": "journal-article" }
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