ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

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To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12620000445976

Ethics application status

Approved

Date submitted

2/04/2020

Date registered

6/04/2020

Date last updated

21/05/2024

Date data sharing statement initially provided

6/04/2020

Type of registration

Prospectively registered

Titles & IDs

Public title

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)

Scientific title

Australasian COVID-19 Trial (ASCOT): An International Multi-Centre Randomised Adaptive Platform Clinical Trial to Assess Different Treatment Regimens on the Clinical, Virological and Immunological Outcomes in Patients Diagnosed with SARS-CoV-2 Infection (COVID-19).

Secondary ID [1]

NCT04483960.

Universal Trial Number (UTN)

U1111-1250-5165

Trial acronym

ASCOT

Linked study record

Health condition

Health condition(s) or problem(s) studied:

COVID-19 (SARS-CoV-2)

Condition category

Condition code

Infection

Other infectious diseases

Respiratory

Other respiratory disorders / diseases

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatments in ASCOT ADAPT are divided into different intervention domains. Depending on eligibility and availability of the invention at participating sites, participants are randomised to receive one intervention from each domain, and therefore, can receive a combination of treatments.

(Domain Closed) Domain A - Antiviral Interventions:
Intervention 1A
Intervention Type: Drug
Intervention Administration: Intravenous infusion
Intervention Name: Nafamostat
Intervention Description: Continuous infusion of nafamostat (0.2mg/kg/hr) for 7 days or until hospital discharge (whichever is earlier).
Intervention Adherence: direct supervision while in hospital.

Intervention 2A
Intervention Type: Other
Intervention Administration: Various
Intervention Name: Standard of care
Intervention Description: Routine usual medical care given by medical doctors to treat and control symptoms (i.e. medications for pain or oxygen therapy) of COVID-19.
Intervention Adherence: direct supervision while in hospital.

(Domain Never Opened) Domain B - Therapeutic Antibody Interventions:
Intervention 1B
Intervention Type: Biological
Intervention Administration: Intravenous infusion
Intervention Name: Hyperimmune globulin
Intervention Description: 2 doses of 30mL (3x10mL vials) of COVID-19 Hyper-Immunoglobulin (Human) given over 2 days within 48 hours of randomisation. Three vials will have approximately 10500 AU of neutralising antibodies, equivalent to approximately 200mL of convalescent plasma.
Intervention Adherence: direct supervision while in hospital.

Intervention 2B
Intervention Type: Other
Intervention Administration: Various
Intervention Name: Standard of care
Intervention Description: Routine usual medical care without antibody therapies, given by medical doctors to treat and control symptoms (i.e. medications for pain or oxygen therapy) of COVID-19.
Intervention Adherence: direct supervision while in hospital.

(Domain Closed) Domain C - Anticoagulation Interventions:
Intervention 1C
Intervention Type: Drug
Intervention Administration: Injection
Intervention Name: Standard dose thromboprophylaxis.
Intervention Description: Standard dose of low molecular weight heparin (LMWH) daily until hospital discharge, admission to intensive care unit (ICU) or for a maximum of 28 days from randomisation. Choice of LMWH according to availability and local practice at the participating site, including Enoxaparin (dose 20mg if <50kg, 40mg if 50-120kg, 60mg if >120kg q24h), Tinzaparin (dose 75IU/kg q24h) or Dalteparin (dose 2500IU if <40kg, 5000IU if 40-120kg, 7500IU if >120kg q24h)
Intervention Adherence: direct supervision while in hospital.

Intervention 2C
Intervention Type: Drug
Intervention Administration: Injection
Intervention Name: Intermediate dose thromboprophylaxis.
Intervention Description: Intermediate dose of LMWH daily until hospital discharge, admission to ICU or for a maximum of 28 days from randomisation. Choice of LMWH according to availability and local practice at the participating site, including Enoxaparin (dose 40mg q24h if <50kg, 40mg q12h or 80mg q24h if 50-120kg, 60mg q12h or 120mg q24h if >120kg), Tinzaparin (dose 125IU/kg/day) or Dalteparin (dose 5000IU q24h if <40kg, 5000IU q12h or 10,000IU q24h if 40-120kg, 7500IU q12h or 15,000IU q24h if >120kg)
Intervention Adherence: direct supervision while in hospital.

Intervention 3C
Intervention Type: Drug
Intervention Administration: Injection
Intervention Name: Therapeutic anticoagulation
Intervention Description: Therapeutic anticoagulation administered with LMWH daily until hospital discharge, admission to ICU or for a maximum of 28 days from randomisation. Choice of LMWH according to availability and local practice at the participating site, including Enoxaparin (dose 1mg/kg q12h or 1.5mg/kg q24h), Tinzaparin (dose 175IU/kg q24h) or Dalteparin (dose 100IU/kg q12h or 200IU/kg q24h)
Intervention Adherence: direct supervision while in hospital.

Domain Q - COVID-19 Antiviral II Domain
Intervention 1Q
Intervention Type: Other
Intervention Administration: Other
Intervention Name: No antiviral agent
Intervention Description: Patients assigned to this intervention are not to receive antiviral agents intended to be active against SARS-CoV-2 for 28 days or until hospital discharge, whichever occurs first.
Intervention Adherence: direct supervision while in hospital.

Intervention 2Q
Intervention Type: Drug
Intervention Administration: Oral/enteral
Intervention Name: Nirmatrelvir-ritonavir
Intervention Description: The dose of nirmatrelvir-ritonavir is dependent on renal function. Participants will receive 100mg BD of Ritonavir and either 150mg BD (if eGFR 30-59 mL/min/1.73m2) or 300mg BD (eGFR = 60 mL/min/1.73m2) of Nirmatrelvir. Investigators are advised to consider withholding treatment if participant’s eGFR < 30 mL/min/1.73m2.
Intervention Adherence: direct supervision while in hospital.

Intervention 3Q
Intervention Type: Drug
Intervention Administration: Intravenous infusion
Intervention Name: Remdesivir
Intervention Description: The dose of intravenous remdesivir is 200 mg on day 1 followed by 100 mg daily for a further four doses (i.e., for five doses in total) or until hospital discharge, whichever occurs first. Remdesivir will be administered as an intravenous infusion via a central or peripheral venous catheter over a 30-120 minute period, as per local practice
Intervention Adherence: direct supervision while in hospital.

Intervention 4Q
Intervention Type: Drug
Intervention Administration: Intravenous infusion and oral/enteral
Intervention Name: Nirmatrelvir-ritonavir + remdesivir
Intervention Description: The drug dosing and administration for participants receiving oral nirmatrelvir-ritonavir + intravenous remdesivir is the same as outlined in 2Q and 3Q above.
Intervention Adherence: direct supervision while in hospital.

Intervention code [1]

Treatment: Drugs

Intervention code [2]

Treatment: Other

Comparator / control treatment

Treatment contrasts will be:
-Superiority: Intervention is better than alternative interventions within a domain for that strata group.
-Inferiority: Intervention is worse than alternative interventions within a domain for that strata group.
-Equivalence: Intervention is not better or worse (i.e. it is equivalent) to at least one other alternative intervention within a domain for that strata group

Control group

Active

Outcomes

Primary outcome [1]

A hierarchical ordinal scale that is a composite of mortality during the acute hospital
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.

Timepoint [1]

End of study day 21 after randomisation

Secondary outcome [1]

Core Secondary Outcome:
Modified WHO ordinal outcome scale at day 14 after randomisation
The modified ordinal score is:
1. Not hospitalised
2. Hospitalised
3. Hospitalised, requiring supplemental oxygen
4. Hospitalised, on non-invasive ventilation or high flow oxygen devices
5. Hospitalised, on invasive mechanical ventilation or ECMO
6. Death.
Note. Admission to a Hospital in the Home unit is not counted as hospitalisation for the purposes of this ordinal scale. Patients who have been admitted to hospital and transferred to a Hospital in the Home unit will be assessed as either ordinal score 1 or 2.
Data collected from patient medical records.

Timepoint [1]

14 days after randomisation

Secondary outcome [2]

Core secondary outcome:

All-cause mortality

Timepoint [2]

28, 90 and 180 days after randomisation

Secondary outcome [3]

Core Secondary Outcomes:
Days alive and free of hospital, as it applies to the index hospital admission, by 28 days after randomisation

Note 1. Days spent in a Hospital in the Home unit will not be counted as days in hospital as hospital means ‘acute-care hospital’ for the purposes of this endpoint.

Note 2. If patient is discharged prior to day 28, it will be assumed the patient has not been readmitted to hospital.

Timepoint [3]

By 28 days after randomisation

Secondary outcome [4]

Core Secondary Outcome:
Days alive and free of supplemental oxygen, invasive or non-invasive ventilation by 28 days after randomisation
Note. If patient is discharged prior to day 28, it will be assumed that they have not received any supplemental oxygen, invasive or non-invasive ventilation since discharge.

Timepoint [4]

By 28 days after randomisation

Secondary outcome [5]

[No longer collected. Domain closed] Antiviral domain-specific secondary outcome: Viral clearance. Proportion of patients with negative SARS-CoV-2 RT-PCR at day 3 (post randomisation) and day 7 from upper or lower respiratory tract samples, for those with results available.

Timepoint [5]

Day 3 and day 7 post randomisation

Secondary outcome [6]

[No longer collected. Domain never opened]. Antibody domain-specific secondary outcome: Confirmed arterial thrombosis (acute myocardial infarction, ischemic cerebrovascular event, other) as assessed by patient medical records.

Timepoint [6]

Up to day 28

Secondary outcome [7]

[No longer collected. Domain never opened]. Antibody domain-specific secondary outcome: Haemolysis - defined as fever and other symptoms/signs of haemolysis confirmed by one or more of the following: • Fall of haemoglobin • Rise in lactic dehydrogenase • Rise in bilirubin • Positive direct antiglobulin test • Positive crossmatch Haemolysis within 72 hours Assessed using patient medical records.

Timepoint [7]

Within 72 hours of last transfusion

Secondary outcome [8]

[No longer collected. Domain never opened]. Antibody domain-specific secondary outcome: Occurrence of any of the following serious treatment-related adverse events (assessed via medical records): 1) Serious allergic reaction or anaphylaxis; 2) Transfusion-related acute lung injury (TRALI)

Timepoint [8]

Within 24 hours of intervention administration

Secondary outcome [9]

[No longer collected. Domain closed]. Antiviral domain-specific secondary outcome: Viral load. Changes in cycle threshold value in RT-PCR for SARS-CoV-2 from baseline to day 3 and from baseline to day 7, for those with results available from the same respiratory tract sample type.

Timepoint [9]

Baseline and Day 3 and day 7 post randomisation

Secondary outcome [10]

[No longer collected. Domain closed]. Antiviral domain-specific secondary outcome: Safety: Elevation of Alanine Transaminase (ALT) or Aspartate Transaminase (AST) to >5x upper limit of normal assessed via medical records

Timepoint [10]

At any time while admitted to hospital (censored at day of discharge)

Secondary outcome [11]

[No longer collected. Domain closed]. Anticoagulation domain-specific secondary outcome: Confirmed deep venous thrombosis, assessed via medical records.

Timepoint [11]

Up to day 28 post randomisation

Secondary outcome [12]

[No longer collected. Domain closed]. Anticoagulation domain-specific secondary outcome: Other confirmed thrombotic event up to 28 days after randomisation.

Timepoint [12]

During index hospitalisation, up to day 28 post randomisation.

Secondary outcome [13]

[No longer collected] Core secondary outcome: Time to clinical recovery. Time to clinical recovery is defined as the first day, during the 28 days after enrolment, on which a patient satisfies categories 1, 2, or 3 on the WHO eight-point ordinal outcome scale. For the purposes of this outcome measure, it will be assumed that the participant is not hospitalised on the first day following discharge.

Timepoint [13]

up to 28 days after randomisation

Secondary outcome [14]

Core secondary outcome:

Presence of patient-reported outcome of shortness of breath.

1. Dichotomous comparison of a subjective measure of shortness of breath such as: “Are you currently experiencing shortness of breath that you didn’t have before you got COVID, or which is worse now than before you got COVID?”

2. Ordinal comparison of the modified Medical Research Council (mMRC) breathlessness scale:
0=I only get breathless with strenuous exercise;
1=I get short of breath when hurrying on level ground or walking up a slight hill;
2=On level ground, I walk slower than people of the same age because of breathlessness, or I have to stop for breath when walking at my own pace on the level;
3=I stop for breath after walking about 100 metres or after a few minutes on level ground;
4=I am too breathless to leave the house or I am breathless when dressing or undressing

Timepoint [14]

180 days after randomisation.

Secondary outcome [15]

Core secondary outcome:

Quality of life as measured by EQ-5D-5L questionnaire

Timepoint [15]

180 days after randomisation

Secondary outcome [16]

[No longer collected. Domain never opened]. Antibody domain-specific secondary outcome: Confirmed venous thrombosis (deep vein thrombosis, pulmonary embolus, other) as assessed by patient medical records.

Timepoint [16]

Up to day 28

Secondary outcome [17]

[No longer collected. Domain closed]. Antiviral domain-specific secondary outcome: Safety: Elevation of serum potassium to >5.5 mmol/L (assessed via medical records)

Timepoint [17]

While admitted to hospital (censored at day of discharge).

Secondary outcome [18]

[No longer collected. Domain closed]. Antiviral domain-specific secondary outcome: Safety: Decrease of serum sodium to <125 mmol/L (assessed via medical records)

Timepoint [18]

While admitted to hospital (censored at day of discharge)

Secondary outcome [19]

[No longer collected. Domain closed]. Antiviral domain-specific secondary outcome: Safety: Major bleeding as defined by the International Society on Thrombosis and Haemostasis (ISTH; assessed via medical records)

Timepoint [19]

While admitted to hospital (censored on day of discharge)

Secondary outcome [20]

[No longer collected. Domain closed]. Antiviral domain-specific secondary outcome: Safety: Thrombophlebitis/vasculitis at IV line site (assessed via medical records).

Timepoint [20]

While admitted to hospital (censored on day of discharge)

Secondary outcome [21]

[No longer collected. Domain closed]. Anticoagulation domain-specific secondary outcome: Confirmed pulmonary embolus assessed via medical records.

Timepoint [21]

Up to 28 days after randomisation

Secondary outcome [22]

[No longer collected. Domain closed]. Anticoagulation domain-specific secondary outcome: Confirmed acute myocardial infarction assessed via medical records.

Timepoint [22]

Up to 28 days after randomisation.

Secondary outcome [23]

[No longer collected. Domain closed]. Anticoagulation domain-specific secondary outcome: Confirmed ischemic cerebrovascular event assessed via medical records.

Timepoint [23]

Up to 28 days after randomisation

Secondary outcome [24]

[No longer collected. Domain closed]. Anticoagulation domain-specific secondary outcome: Confirmed deep vein thrombosis assessed via medical records.

Timepoint [24]

Up to 28 days after randomisation

Secondary outcome [25]

[No longer collected. Domain closed]. Anticoagulation domain-specific secondary outcome: Major bleeding (as defined by ISTH) assessed via medical records.

Timepoint [25]

Up to 28 days after randomisation

Secondary outcome [26]

[No longer collected. Domain closed]. Anticoagulation domain-specific secondary outcome: Clinically relevant non-major bleeding (as defined by ISTH) assessed via medical records.

Timepoint [26]

Up to 28 days after randomisation.

Secondary outcome [27]

[No longer collected. Domain closed]. Anticoagulation domain-specific secondary outcome: Heparin-induced thrombocytopenia during index hospitalisation, assessed via medical records

Timepoint [27]

Up to 28 days after randomisation

Secondary outcome [28]

[No longer collected. Domain closed]. Antiviral domain-specific secondary outcome: Safety: Clinically relevant non-major bleeding (as defined by ISTH) assessed via medical records.

Timepoint [28]

While admitted to hospital (censored on day of discharge)

Secondary outcome [29]

Core Secondary Outcome:
Days alive and free of invasive or non-invasive ventilation or high flow oxygen by 28 days after randomisation. Collected from patient medical records.

Note. If patient is discharged prior to day 28, it will be assumed that they have not received any invasive or non-invasive ventilation since discharge.

Timepoint [29]

Secondary outcome [30]

Timepoint [30]

28 days after randomisation

Secondary outcome [31]

Core Secondary Outcome:
Days alive and free of invasive mechanical ventilation by 28 days after randomisation

Note. If patient is discharged prior to day 28, it will be assumed that they have not received any invasive ventilation since discharge.

Data collected from patient medical records.

Timepoint [31]

28 days after randomisation

Secondary outcome [32]

Timepoint [32]

28 days after randomisation

Secondary outcome [33]

Core Secondary Outcome:
Destination at time of hospital discharge (characterised as home, rehabilitation hospital, nursing home, or long-term care facility, or another acute hospital)
Data collected from patient medical record

Timepoint [33]

28 days after randomisation

Secondary outcome [34]

Timepoint [34]

Discharge

Secondary outcome [35]

Core Secondary Outcome: Admission (or re-admission) to ICU during the index hospitalisation, censored at 90 days post-randomisation. Data collected from patient medical records.

Timepoint [35]

Discharge

Secondary outcome [36]

Core Secondary Outcome: Admission (or re-admission) to ICU during the index hospitalisation, censored at 90 days post-randomisation. Data collected from patient medical records.

Timepoint [36]

During the participant's index hospitalisation. Censored 90 days after randomisation.

Secondary outcome [37]

Core secondary outcome measures for participants admitted to ICU: ICU mortality, censored at 90 days post-randomisation. Data collected from patient medical records.

Timepoint [37]

During the participant's index hospitalisation. Censored 90 days after randomisation.

Secondary outcome [38]

Core secondary outcome measures for participants admitted to ICU: ICU mortality, censored at 90 days post-randomisation. Data collected from patient medical records.

Timepoint [38]

Up to 90 days after randomisation.

Secondary outcome [39]

Core secondary outcome measures for participants admitted to ICU:
ICU length of stay, censored at 90 days post-randomisation. Data collected from patient medical records.

Timepoint [39]

Up to 90 days after randomisation.

Secondary outcome [40]

Core secondary outcome measures for participants admitted to ICU:
ICU length of stay, censored at 90 days post-randomisation. Data collected from patient medical records.

Timepoint [40]

Up to 90 days after randomisation

Secondary outcome [41]

Core secondary outcome measures for participants admitted to ICU:
Ventilator-free days, censored at 28 days post-randomisation. Data collected from patient medical records.

Timepoint [41]

Up to 90 days after randomisation

Secondary outcome [42]

Core secondary outcome measures for participants admitted to ICU:
Ventilator-free days, censored at 28 days post-randomisation. Data collected from patient medical records.

Timepoint [42]

Up to 28 days after randomisation

Secondary outcome [43]

Core secondary outcome measures for participants admitted to ICU:
Organ failure free days. Data collected from patient medical records.

Timepoint [43]

Up to 28 days after randomisation

Secondary outcome [44]

Core secondary outcome measures for participants admitted to ICU:
Organ failure free days. Data collected from patient medical records.

Timepoint [44]

Up to 28 days after randomisation

Secondary outcome [45]

Antiviral II Domain Secondary Outcome:
Length of hospital stay (in days). Data collected from patient medical record.

Timepoint [45]

Up to 28 days after randomisation

Secondary outcome [46]

Antiviral II Domain Secondary Outcome:
Length of hospital stay (in days). Data collected from patient medical record.

Timepoint [46]

During the participant's index hospitalisation. Censored 90 days after enrolment.

Secondary outcome [47]

Antiviral II Domain Secondary Outcome:
Proportion of participants with baseline respiratory symptoms in whom all acute respiratory symptoms have resolved at study day 7 after randomisation. Data collected from patient medical records or directly from the patient or proxy.

Note 1. Respiratory symptoms are defined as one or more of: cough, sore throat, runny nose sneezing, shortness of breath or chest pain. “Acute” means the symptom in question is not usually present in that individual, or during the current COVID episode was substantially worse or more frequent than usual.
Note 2. Resolution of all acute respiratory symptoms means return to baseline state – not necessarily the absence of all respiratory symptoms.
Note 3. Ongoing non-respiratory symptoms (such as fatigue, anorexia, delirium, diarrhea) are not counted as part of this endpoint.

Timepoint [47]

During the participant's index hospitalisation. Censored 90 days after enrolment.

Secondary outcome [48]

Timepoint [48]

7 days after randomisation

Eligibility

Key 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

Minimum age

No limit

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key 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

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Central randomisation by computer

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Participants may be randomised using response adaptive randomisation (RAR), that is the ratio of randomisation to each regimen will be proportional to the posterior probability that it is the optimal regimen for that participant, depending on their State and Strata membership. At commencement, initial randomisation ratios will be equal across all regimens; in other words, no assumptions will be made about the relative efficacy of each intervention prior to the first examination of the accumulating data.

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Factorial

Other design features

Phase

Phase 3

Type of endpoint/s

Efficacy

Statistical methods / analysis

Regular adaptive analyses will be undertaken using a Bayesian Hierarchical Model that can estimate the probability of superiority, efficacy, inferiority, equivalence, non-inferiority, harm or futility relative to pre-defined reference levels.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

10/04/2020

Actual

28/07/2020

Date of last participant enrolment

Anticipated

4/07/2025

Actual

Date of last data collection

Anticipated

31/12/2025

Actual

Sample size

Target

2200

Accrual to date

1606

Final

Recruitment in Australia

Recruitment state(s)

ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Recruitment hospital [1]

Blacktown Hospital - Blacktown

Recruitment hospital [2]

John Hunter Hospital - New Lambton

Recruitment hospital [3]

Liverpool Hospital - Liverpool

Recruitment hospital [4]

Nepean Hospital - Kingswood

Recruitment hospital [5]

Prince of Wales Hospital - Randwick

Recruitment hospital [6]

St George Hospital - Kogarah

Recruitment hospital [7]

Wollongong Hospital - Wollongong

Recruitment hospital [8]

Westmead Hospital - Westmead

Recruitment hospital [9]

Royal Brisbane & Womens Hospital - Herston

Recruitment hospital [10]

The Prince Charles Hospital - Chermside

Recruitment hospital [11]

Lyell McEwin Hospital - Elizabeth Vale

Recruitment hospital [12]

Royal Perth Hospital - Perth

Recruitment hospital [13]

Royal Melbourne Hospital - Royal Park campus - Parkville

Recruitment hospital [14]

Monash Medical Centre - Clayton campus - Clayton

Recruitment hospital [15]

Dandenong Hospital - Dandenong

Recruitment hospital [16]

Casey Hospital - Berwick

Recruitment hospital [17]

The Northern Hospital - Epping

Recruitment hospital [18]

Footscray Hospital - Footscray

Recruitment hospital [19]

Sunshine Hospital - St Albans

Recruitment hospital [20]

Ballarat Health Services (Base Hospital) - Ballarat Central

Recruitment hospital [21]

Campbelltown Hospital - Campbelltown

Recruitment hospital [22]

Wagga Wagga Base Hospital - Wagga Wagga

Recruitment hospital [23]

Royal North Shore Hospital - St Leonards

Recruitment hospital [24]

Royal Darwin Hospital - Tiwi

Recruitment postcode(s) [1]

2148 - Blacktown

Recruitment postcode(s) [2]

2305 - New Lambton

Recruitment postcode(s) [3]

2170 - Liverpool

Recruitment postcode(s) [4]

2747 - Kingswood

Recruitment postcode(s) [5]

2031 - Randwick

Recruitment postcode(s) [6]

2217 - Kogarah

Recruitment postcode(s) [7]

2500 - Wollongong

Recruitment postcode(s) [8]

2145 - Westmead

Recruitment postcode(s) [9]

4029 - Herston

Recruitment postcode(s) [10]

4032 - Chermside

Recruitment postcode(s) [11]

5112 - Elizabeth Vale

Recruitment postcode(s) [12]

6000 - Perth

Recruitment postcode(s) [13]

3052 - Parkville

Recruitment postcode(s) [14]

3168 - Clayton

Recruitment postcode(s) [15]

3175 - Dandenong

Recruitment postcode(s) [16]

3806 - Berwick

Recruitment postcode(s) [17]

3076 - Epping

Recruitment postcode(s) [18]

3011 - Footscray

Recruitment postcode(s) [19]

3021 - St Albans

Recruitment postcode(s) [20]

3350 - Ballarat Central

Recruitment postcode(s) [21]

2560 - Campbelltown

Recruitment postcode(s) [22]

2650 - Wagga Wagga

Recruitment postcode(s) [23]

2065 - St Leonards

Recruitment postcode(s) [24]

0810 - Tiwi

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Funding & Sponsors

Funding source category [1]

University

Name [1]

University of Melbourne

Address [1]

Parkville, VIC 3010

Country [1]

Australia

Funding source category [2]

University

Name [2]

University of Queensland

Address [2]

Centre for Clinical Research
Building 71/918, Royal Brisbane Women's Campus
Herston, QLD 4029

Country [2]

Australia

Funding source category [3]

Other

Name [3]

Hunter Medical Research Institute: a partnership between the University of Newcastle, Hunter New England Local Health District

Address [3]

Lot 1, Kookaburra Cct
New Lambton Heights NSW 2305

Country [3]

Australia

Funding source category [4]

Charities/Societies/Foundations

Name [4]

The Pratt Foundation

Address [4]

Level 11, 2 Southbank Bvd
Southbank VIC 3006

Country [4]

Australia

Funding source category [5]

Charities/Societies/Foundations

Name [5]

Royal Brisbane Women's Hospital Foundation

Address [5]

Block 20, Royal Brisbane Women's Hospital
Butterfield St, Herston, QLD 4029

Country [5]

Australia

Funding source category [6]

Charities/Societies/Foundations

Name [6]

Hospital Research Foundation

Address [6]

60 Woodville Rd,
Woodville SA 5011

Country [6]

Australia

Funding source category [7]

Charities/Societies/Foundations

Name [7]

The Minderoo Foundation

Address [7]

PO Box 3155, Broadway Nedlands, WA 6009

Country [7]

Australia

Funding source category [8]

Commercial sector/Industry

Name [8]

BHP

Address [8]

171 Collins Street
Melbourne Victoria 3000

Country [8]

Australia

Funding source category [9]

Other

Name [9]

New Zealand Health Research Council

Address [9]

PO Box 5541, Victoria Street West, Auckland 1142

Country [9]

New Zealand

Funding source category [10]

Charities/Societies/Foundations

Name [10]

Macquarie Group Foundation

Address [10]

Level 4, 1 Martin Place
Sydney NSW 2000

Country [10]

Australia

Funding source category [11]

Government body

Name [11]

Medical Research Future Fund

Address [11]

Department of Health
GPO Box 9848
Canberra ACT 2601
Australia

Country [11]

Australia

Funding source category [12]

Government body

Name [12]

NSW Office for Health and Medical Research (OHMR)

Address [12]

Country [12]

Australia

Funding source category [13]

Government body

Name [13]

Victorian State Government

Address [13]

Country [13]

Australia

Primary sponsor type

University

Name

University of Melbourne

Address

Parkville, VIC, 3050

Country

Australia

Secondary sponsor category [1]

Other

Name [1]

Aotearoa Clinical Trials

Address [1]

Aotearoa Clinical Trials, Private Bag 93311, Otahuhu 1640 Auckland, New Zealand

Country [1]

New Zealand

Secondary sponsor category [2]

Other

Name [2]

The George Institute for Global Health

Address [2]

Level 5, 1 King Street
Newtown 2042
NSW, Australia

Country [2]

Australia

Other collaborator category [1]

Other Collaborative groups

Name [1]

The Australasian Society for Infectious Diseases Clinical Research Network (ASID CRN)

Address [1]

Suite 302, Level 3, 478 George Street
Sydney NSW 2000
Australia

Country [1]

Australia

Other collaborator category [2]

Other Collaborative groups

Name [2]

Hunter Medical Research Institute (HMRI)

Address [2]

Country [2]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Melbourne Health Human Research Ethics Committee

Ethics committee address [1]

Royal Melbourne Hospital Office for Research
CITY CAMPUS
Level 2
South West
300 Grattan Street
Parkville Victoria 3050

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

20/03/2020

Approval date [1]

03/04/2020

Ethics approval number [1]

HREC/62646/MH-2020

Ethics committee name [2]

Sydney Local Health District Ethics Review Committee (RPAH Zone)

Ethics committee address [2]

https://www.slhd.nsw.gov.au/rpa/research/

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

18/07/2023

Approval date [2]

15/08/2023

Ethics approval number [2]

2023/ETH01712

Summary

Brief summary

ASCOT is an investigator-initiated, multi-centre, open-label, randomised controlled Bayesian adaptive platform trial. The aim of the trial is to identify the best regimen (combination of interventions) to treat adults hospitalised with COVID-19.

Trial website

https://www.ascot-trial.edu.au/

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

A/Prof Steven Tong

Address

The Peter Doherty Institute for Infection and Immunity
792 Elizabeth Street
Melbourne, Victoria 3000

Country

Australia

Phone

+61 03 9342 9406

Fax

steven.tong@unimelb.edu.au

Contact person for public queries

Name

Steven Tong

Address

The Peter Doherty Institute for Infection and Immunity
792 Elizabeth Street
Melbourne, Victoria 3000

Country

Australia

Phone

+61 03 9342 9406

Fax

ascot-team@unimelb.edu.au

Contact person for scientific queries

Name

Steven Tong

Address

The Peter Doherty Institute for Infection and Immunity
792 Elizabeth Street
Melbourne, Victoria 3000

Country

Australia

Phone

+61 03 9342 9406

Fax

steven.tong@unimelb.edu.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

The trial steering committee will be the custodians of the final trial dataset. No-one outside the trial steering committee will be given access to the data without the permission of the trial steering committee. No identifying data will be given to any third parties at any stage.

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Clinical trials for the prevention and treatment of COVID-19: current state of play.	2020	https://dx.doi.org/10.5694/mja2.50673
Embase	The Australasian COVID-19 Trial (ASCOT) to assess clinical outcomes in hospitalised patients with SARS-CoV-2 infection (COVID-19) treated with lopinavir/ritonavir and/or hydroxychloroquine compared to standard of care: A structured summary of a study protocol for a randomised controlled trial.	2020	https://dx.doi.org/10.1186/s13063-020-04576-9
Embase	Efficacy and safety outcomes of proposed randomized controlled trials investigating hydroxychloroquine and chloroquine during the early stages of the COVID-19 pandemic.	2021	https://dx.doi.org/10.1111/bcp.14598
Embase	ASCOT ADAPT study of COVID-19 therapeutics in hospitalised patients: an international multicentre adaptive platform trial.	2022	https://dx.doi.org/10.1186/s13063-022-06929-y
Embase	Nafamostat Mesylate for Treatment of COVID-19 in Hospitalised Patients: A Structured, Narrative Review.	2022	https://dx.doi.org/10.1007/s40262-022-01170-x

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added automatically