COVID-19; antiviral; primary healthcare; randomized controlled trial; Family Practice
Abstract :
[en] [en] BACKGROUND: 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.
AIM: To explore which factors contributed to the premature termination.
DESIGN & SETTING: General practice in Belgium.
METHOD: Patients were randomised to camostat or placebo (patients and physicians blinded) between June 2021 and July 2022; a third arm evaluating molnupiravir (open label) was opened in March 2022. The outcome assessor was blinded for all comparisons except for the patient reported outcomes in case of molnupiravir. The authors analysed available trial data and evaluated trial context, implementation, and mechanisms of impact based on semi-structured interviews with trial stakeholders.
RESULTS: 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; and 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.
CONCLUSION: The DAWN antivirals trial was stopped prematurely. Although many barriers were related to the pandemic itself, hurdles such as a 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 standardisation of processes.
Disciplines :
General & internal medicine
Author, co-author :
Tare, Dajana; Academic Centre for General Practice, KU Leuven, Belgium
Coenen, Samuel ; Centre for General Practice, Department of Family Medicine and Population Health (FAMPOP), University of Antwerp, Antwerpen, Belgium
De Sutter, An; Department of Public Health and Primary Care, Ghent University, KU Leuven, Belgium
Heytens, Stefan; Department of Public Health and Primary Care, Ghent University, KU Leuven, Belgium
Devroey, Dirk; Primary Care, Vrije Universiteit Brussel, Ixelles, Belgium
Buret, Laetitia ; Université de Liège - ULiège > Département des sciences cliniques > Médecine générale
Schoenmakers, Birgitte ; Academic Centre for General Practice, KU Leuven, Belgium
Delvaux, Nicolas; Academic Centre for General Practice, KU Leuven, Belgium
Verbakel, Jan Y ; Academic Centre for General Practice, KU Leuven, Belgium
Bogaerts, Kris; Department of Public Health and Primary Care, I-BioStat, KU Leuven, Leuven, Belgium
van den Bruel, Ann ; Academic Centre for General Practice, KU Leuven, Belgium ann.vandenbruel@kuleuven.be
Language :
English
Title :
The DAWN antivirals trial: process evaluation of a COVID-19 trial in general practice.
The DAWN antivirals trial was a phase III, randomised placebo-controlled trial of antivirals in moderately ill COVID-19 patients presenting to general practice (clinical trials ID NCT04730206). The aim was to find a repurposing drug that would be suitable for widespread use in COVID-19 patients treated in general practice. The trial was funded by KCE Trials, a national funding body, and sponsored by the KU Leuven in collaboration with four other university groups across Belgium. Preparations for the study started in the third quarter of 2020, and the study opened for recruitment in the second quarter of 2021.The authors would like to acknowledge all the GPs, study nurses, and staff involved in the DAWN antivirals trial and process evaluation. The DAWN antivirals study (COV20-1279) is an independent research study funded by the Belgian Health Care Knowledge Centre under the KCE Trials Programme. The views expressed in this publication are those of the author(s) and not necessarily those of Belgian Health Care Knowledge Centre.
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