Australasian COVID-19 Trial (ASCOT): A multi-centre randomised adaptive platform clinical trial to assess clinical, virological and immunological outcomes in patients with SARS-CoV-2 infection (COVID-19)

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 2200

Inclusion Criteria

Core Platform Inclusion Criteria (all participants must meet the following):
Adult (as defined by local jurisdiction) patient admitted to hospital with acute illness and suspected or proven SARS-CoV-2 infection.

Antiviral II Inclusion Criteria (all patients at sites participating in the Antiviral II Domain must meet the following) :
SARS-CoV-2 infection has been confirmed by positive rapid antigen test OR polymerase chain reaction test within the last 7 days

Exclusion Criteria

A. Core Platform Exclusion Criteria (all participants must not meet the following):
1. Death is deemed to be imminent and inevitable during the next 24 hours AND one or more of the patient, substitute decision maker or attending physician are not committed to full active treatment
2. Patient is expected to be discharged from hospital today or tomorrow
3. More than 14 days have elapsed while admitted to hospital with symptoms of an acute illness due to proven SARS-CoV-2 infection
4. Previous participation in this trial, or another trial that is analysed within the same statistical model as this trial, within the last 90 days

B. Antiviral II Domain Exclusion Criteria (all patients at sites participating in the Antiviral II Domain must not meet the following):
1.Severe renal impairment, defined as eGFR<30ml/min or receipt of renal replacement therapy
2.Severe hepatic impairment, defined as proven or suspected cirrhosis with Child Pugh class of C, OR acute hepatitis, defined as AST or ALT>5 times the upper limit of normal in the testing laboratory.
3.The patient has received, at the time of eligibility assessment, >24h of an antiviral agent intended to have activity against SARS-CoV-2, within the past 7 days
4.The patient is known to be pregnant or breastfeeding
5.The treating clinician believes that participation in the domain would not be in the best interests of the patient

B.1. Antiviral II Domain Non-Immune Suppressed Stratum-specific Exclusion Criteria (all non-immune suppressed patients at sites participating in the Antiviral II Domain must not meet the following):
1. Onset of COVID-related symptoms was more than 7 days (i.e., 168 hours) ago

B2. Antiviral II domain Intervention-specific Exclusion Criteria (All patients at sites participating in the Antiviral II Domain will be excluded from the below interventions if they meet the following):

Will be excluded from receiving Remdesivir if:
1 No venous access is available and none can be created
2 Known hypersensitivity to remdesivir or its excipients

Will be excluded from receiving Nirmatrelvir/ritonavir if:
1 The patient is unable to take, tolerate or absorb oral or enteral medications
2 Known hypersensitivity to any of nirmatrelvir, ritonavir or its excipients
3 Receipt of a concomitant drug with a high-risk interaction with nirmatrelvir-ritonavir which cannot be ceased or substituted.

Will be excluded from receiving no antiviral agent if:
1. The patient is in the Immune Suppressed Stratum
2. The patient is receiving or has received supplemental oxygen on the calendar day of eligibility assessment.
3. The patient is considered by the treating clinician to be at very high risk for progression to severe COVID-19

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
A hierarchical ordinal scale that is a composite of mortality during the acute hospital<br>admission and the duration of organ failure support while admitted to an ICU up until the end of study day 21. Death and duration of organ support collected from patient medical records. [ End of study day 21 after randomisation]

Secondary Outcome Measures