NCT04483960

Australasian COVID-19 Trial (ASCOT) ADAptive Platform Trial

A Multi-centre Randomised Adaptive Platform Clinical Trial to Assess Clinical, Virological and Immunological Outcomes in Patients With SARS-CoV-2 Infection (COVID-19)

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 2,200 (estimated)
• Sponsor: University of Melbourne · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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).

Detailed description

ASCOT is an investigator-initiated, multi-centre, open-label, randomised controlled, Bayesian, adaptive platform trial. The objective of ASCOT is to identify the regimen (combination of interventions) associated with the highest chance of improving clinical outcomes in adults hospitalised with COVID-19. Platform trials allow multiple questions to be evaluated simultaneously and sequentially within the platform, and evaluate interaction between different treatment options, to achieve the goal of determining the optimal combination of treatments for the disease as rapidly as possible. Study treatments are categorised into different treatment domains. The adaptive nature of the trial means treatments within a domain or an entire domain can be removed or added based on accruing data analysed at frequent intervals or based on external evidence. \[Domain Closed\] Intervention domain A (antiviral): Participants will be randomised to receive either i) standard of care without nafamostat; or ii) standard of care with nafamostat \[Never Opened\] Intervention domain B (antibody): Participants will be randomised to receive either i) standard of care without hyperimmune globulin; or ii) standard of care with hyperimmune globulin \[Domain Closed\] Intervention domain C (anticoagulation): Participants will be randomised to receive either i) standard dose thromboprophylaxis; or ii) intermediate dose thromboprophylaxis; or iii) therapeutic anticoagulation Intervention domain Q (Antiviral II): Participants will be randomised to receive either i) no antiviral agents; or ii) oral nirmatrelvir-ritonavir; or iii) intravenous remdesivir iiii) oral nirmatrelvir-ritonavir + Intravenous remdesivir

Conditions

• SARS-CoV-2 Infection (COVID-19)

Interventions

Type	Name	Description
DRUG	(Arm Closed) Nafamostat Mesilate	Nafamostat continuous IV infusion for 7 days or until day of hospital discharge at a dose of 0.2mg/kg/hour. No adjustment in dose is needed for renal impairment, including for renal dialysis. The daily dose of nafamostat should be administered in 500 mL (rate of infusion 20.8 mL/hour) of normal saline. Normal saline is recommended (due to the tendency for patients with COVID-19 towards hyponatraemia) but not mandated, and 5% dextrose would be acceptable if felt clinically appropriate.
DRUG	(Arm Closed) Enoxaparin	Patients will be administered either a standard dose, intermediate dose or therapeutic anticoagulation of low molecular weight heparin (depending on assigned arm), choice of agent according to availability and local practice at the participating site. The maximum dose of Enoxaparin will be 1mg/kg q12h or 1.5mg/kg q24h.
DRUG	(Arm Closed) Dalteparin	Patients will be administered either a standard dose, intermediate dose or therapeutic anticoagulation of low molecular weight heparin (depending on assigned arm), choice of agent according to availability and local practice at the participating site. The maximum dose of Dalteparin will be 100IU/kg q12h or 200IU/kg q24h.
DRUG	(Arm Closed) Tinzaparin	Patients will be administered either a standard dose, intermediate dose or therapeutic anticoagulation of low molecular weight heparin (depending on assigned arm), choice of agent according to availability and local practice at the participating site. The maximum dose of Tinzaparin will be 175IU/kg q24h (not available within Australia).
BIOLOGICAL	(Arm Never Opened) Hyperimmune globulin	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
DRUG	Nirmatrelvir-Ritonavir	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.
DRUG	Remdesivir	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.

Timeline

• Start date: 2020-07-28
• Primary completion: 2025-07-25
• Completion: 2025-12-31
• First posted: 2020-07-23
• Last updated: 2024-05-16

Locations

25 sites across 1 country: Australia