The DAWN Antivirals Trial for Ambulatory COVID-19 Patients

Study Overview
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Brief Summary
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This is a prospective, placebo controlled, individually randomized controlled phase III trial in Primary Care, assessing the efficacy of antivirals, i.e. camostat and molnupiravir, in accelerating recovery in Covid-19 patients.

Detailed Description
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In patients aged 40 years and above and diagnosed with Covid-19 upon study entry, we will evaluate the efficacy of camostat or molnupiravir on recovery within 30 days after randomisation. Participants will be randomly assigned to camostat, molnupiravir or placebo using a computer generated randomisation process. Participants will be treated for 7 days in case of camostat and 5 days in case of molnupiravir, and follow-up will be 30 days.

Official Title
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The DAWN Antivirals Trial: the Efficacy of Antivirals for COVID-19 Infections Presenting to Ambulatory Care: a Randomized Controlled Trial

Conditions
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Covid19, SARS-CoV Infection

Intervention / Treatment
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* Drug: Camostat
* Drug: Placebo
* Drug: Molnupiravir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 40 years or older; At least 2 Covid-19 suggestive symptoms at the time of inclusion, with onset of a maximum of 5 days prior to enrolment, and which cannot be explained by an alternative cause, and defined by the current Sciensano case definition Positive result on PCR test or rapid Ag test in the 7 days before inclusion or at the time of inclusion; Patient is community dwelling; Participant or their proxy is willing and able to give informed consent for participation in the trial; Participant is willing to comply with all trial procedures. Exclusion Criteria: Hospital admission is required at the time of possible recruitment; Positive PCR or rapid antigen test for SARS-CoV-2 in the last 2 months other than a test at recruitment or in the 7 days prior to recruitment; Participating in any other interventional drug clinical study before enrolment in the study; Breastfeeding; Known severe neurological disorder, especially seizures in the last 12 months; Known allergy to camostat or molnupiravir; Previous adverse reaction to, or currently taking, camostat or molnupiravir; Patients in palliative care; Pregnant women or women of childbearing potential who may become pregnant during the trial and don't agree to use any of the effective contraceptive measures lised above; Judgement of the recruiting clinician deems participant ineligible.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Camostat<br>4 x 200 milligram per day for 7 days | Drug: Camostat<br>* 100 milligram tablets<br>|
| Placebo Comparator: Placebo<br>4 x per day for 7 days | Drug: Placebo<br>* oral tablets, identical in size and shape<br>|
| Experimental: Molnupiravir<br>2 x 800 milligram per day for 5 days | Drug: Molnupiravir<br>* 200 milligram tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first self-reported recovery within 30 days after randomisation |  | within 30 days after randomisation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause unplanned hospital admission for at least 24 hours |  | within 30 days after randomisation | 
| All-cause mortality |  | within 30 days after randomisation | 
| Health status | Score on the World Health Organisation (WHO) clinical progression scale: measure of illness severity across a range from 0 (not infected) to 10 (dead) where lower scores indicate a better outcome. | at 8 days and 30 days after randomization | 
| Oxygen administration in the home setting | Number of patients who had oxygen at least once | over a period of 30 days after randomization | 
| All-cause mortality at 1 year after randomization |  | at 1 year | 
| Cardiovascular and thromboembolic complications | Number of events | within 7 days and 30 days after randomization | 
| Symptom duration for each individual symptom | Duration of symptoms reported by the patient in the patient diary as being present since randomisation | over a period of 30 days after randomization | 
| Duration of hospital admission for those admitted to hospital | Length of stay | over a period of 30 days after randomization | 
| Health services usage | Number of contacts with general practitioners, out-of-hours services, emergency department visits, specialist assessments | over a period of 30 days after randomization | 
| Consumption of antibiotics | Antibiotic consumption expressed in defined daily dose | over a period of 30 days after randomisation | 
| Participants' quality of life | Euroqol EQ-5D-5L: The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems, where higher scores indicate a better outcome | at 7 days and 30 days after randomization | 
| Time to sustained recovery within 14 days | time from randomization to self-reported recovery within 14 days and remaining recovered until day 30 after randomisation. | within 30 days after randomisation | 
| At least once ventilated |  | over a period of 30 days after randomization | 
| Admission to ICU |  | over a period of 30 days after randomization | 
| All-cause unplanned hospital admission for at least 24 hours or all-cause mortality within 30 days of randomization |  | over a period of 30 days after randomization |