Australasian COVID-19 Trial (ASCOT) ADAptive Platform Trial

• Status: Recruiting
• Trial end date: 2022-12-31
• Target enrollment: 0
• Participant gender: All

Summary

An International Multi-Centre Randomised Adaptive Platform Clinical Trial to Assess the Clinical, Virological and Immunological Outcomes in Patients with SARS-CoV-2 Infection (COVID-19).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Melbourne
• Collaborators: Australasian Society for Infectious Diseases; Hunter Medical Research Institute; Middlemore Clinical Trials; The George Institute; The Peter Doherty Institute for Infection and Immunity; The University of Queensland
• Treatments: Dalteparin; Enoxaparin; Heparin, Low-Molecular-Weight; Hydroxychloroquine; Lopinavir; Nafamostat; Ritonavir; Tinzaparin

Criteria

Platform Inclusion Criteria:

1. Age ≥ 18 years

2. Admitted to an acute-care hospital

3. Confirmed SARS-CoV-2 by nucleic acid testing in the past 14 days

4. Able to be randomised within 14 days of symptom onset

5. At least one symptom or sign attributable to SARS-CoV-2 infection

Exclusion Criteria:

A. Overall platform exclusions:

1. Currently receiving acute intensive respiratory support (invasive or non-invasive mechanical ventilation) or vasopressor/inotropic support. Note, participants already on community based non-invasive ventilation (either CPAP or BiPAP) can still be recruited. Humidified high flow nasal oxygen will not be considered an exclusion criterion.

2. Previous participation in the trial

3. Treating team deems enrolment in the study is not in the best interests of the patient

4. Death is deemed to be imminent and inevitable within the next 24 hours

5. Either the patient or their primary treating clinician are not committed to active treatment.

This criterion seeks to exclude those patients where supportive comfort measures only are being provided. Patients who are planned for active ward management with a clear aim to improve survival, even if intensive care unit level support is not being offered, should still be included.

B. Domain A (Antiviral) intervention-level exclusions:

Criteria that exclude a patient from one or more interventions are:

Nafamostat:

• Known current decompensated liver disease (Child-Pugh B or C)

• The treating clinician intends to continue or commence therapeutic anticoagulation

• A current or recurrent condition with a high risk of major bleeding (e.g. bleeding disorder), or a baseline coagulation profile (within the previous 3 days) that indicates a high risk of bleeding, that would be considered a contraindication to receive therapeutic anticoagulation

• Serum Potassium >5.5 mmol/L (based on most recent blood test result collected as part of routine care within the previous 3 days)

• Serum Sodium <120 mmol/L (based on most recent blood test result collected as part of routine care within the previous 3 days)

• Hypersensitivity to nafamostat

• Pregnancy or breastfeeding

• Currently receiving or have received nafamostat in the past 7 days

• Decompensated heart failure or renal dialysis and clinician believes an extra 500mL fluid/day would be detrimental There are no domain-level exclusions for the antiviral domain.

C. Domain B (Antibody) domain-level exclusions:

Patients will be excluded from this domain if they have any of the following:

• Participant has already received treatment with SARS-CoV-2-specific immunoglobulin therapy (convalescent plasma, hyperimmune globulin or monoclonal antibody) within 3 months prior to enrolment;

• Treating team deems enrolment in antibody intervention is not in the best interests of the patient.

• Participant has received a SARS-COV-2 vaccine within the prior 30 days

Domain B (Antibody) intervention-level exclusions:

The following are intervention exclusions:

• Known previous history of serious allergic reaction to blood product transfusion, intravenous immunoglobulin or other injectable form of IgG will exclude a patient from hyperimmune globulin;

• Known personal or religious objections to receiving blood products will exclude a patient from receiving hyperimmune globulin;

• Prior history of a thrombotic event (including acute coronary sydromes, cerebrovascular syndromes, pulmonary or deep venous thrombosis) within the prior 30 days of randomisations will exclude a patient from hyperimmune globulin;

• Having a creatinine clearance of less than 50mL/min will exclude a patient from receiving hyperimmune globulin

D. Domain C (Anticoagulation) domain-level exclusions:

Patients will be excluded from this domain if they have any of the following:

• Receiving dual antiplatelet therapy

• The treating clinician intends to continue or commence therapeutic anticoagulation

• Contraindication to receiving low molecular weight heparin or unfractionated heparin, including the known or suspected history of heparin-induced thrombocytopenia or other adverse reaction to prior heparin exposure such as hypersensitivity

• Severe thrombocytopenia (platelet count less than 530 x 109/L)

• History of intracranial haemorrhage in the previous 3 months

• Severe renal impairment, defined as estimated glomerular filtration rate less than 15ml/min/1.73m2

• A current or recurrent condition with a high risk of major bleeding (e.g. bleeding disorder), or a baseline coagulation profile (within the previous 3 days) that indicates a high risk of bleeding, that would be considered a contraindication to receive therapeutic anticoagulation