The DAWN Antivirals Trial for Ambulatory COVID-19 Patients (DAWN)

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

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.

Study Overview

• Status: Terminated
• Conditions: Covid19; SARS-CoV Infection
• Intervention / Treatment: Drug: Camostat; Drug: Placebo; Drug: Molnupiravir

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • KU Leuven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: KU Leuven
• Collaborators: University Ghent; Vrije Universiteit Brussel; Universiteit Antwerpen; Université de Liège

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2021
• Primary Completion (Actual): July 13, 2022
• Study Completion (Actual): July 13, 2022

Study Registration Dates

• First Submitted: January 28, 2021
• First Submitted That Met QC Criteria: January 28, 2021
• First Posted (Actual): January 29, 2021

Study Record Updates

• Last Update Posted (Actual): October 3, 2022
• Last Update Submitted That Met QC Criteria: September 29, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Severe Acute Respiratory Syndrome; COVID-19; Infections; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Trypsin Inhibitors; Camostat
• Other Study ID Numbers: S64445

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No