ASCOT Trial Dataset - hospitalised adults: primary and core secondary clinical outcomes(domain‑specific)

Intervention

Intervention code Treatment: Drugs - (Arm Closed) Nafamostat Mesilate , Treatment: Drugs - (Arm Closed) Enoxaparin , Treatment: Drugs - (Arm Closed) Dalteparin , Treatment: Drugs - (Arm Closed) Tinzaparin , Treatment: Other - (Arm Never Opened) Hyperimmune globulin , Treatment: Drugs - Nirmatrelvir-Ritonavir , Treatment: Drugs - Remdesivir

(Arm Closed) Antiviral - Standard of care No intervention Standard of care without nafamostat mesilate (Arm Closed) Antiviral - nafamostat mesilate Experimental 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 t .... (Arm Closed) Antiviral - Standard of care No intervention Standard of care without nafamostat mesilate (Arm Closed) Antiviral - nafamostat mesilate Experimental 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. (Arm Closed) Anticoagulation - standard dose thromboprophylaxis Active comparator Patients will be administered a standard thromboprophylactic dose of low molecular weight heparin, choice of agent according to availability and local practice at the participating site. (Arm Closed) Anticoagulation - intermediate dose thromboprophylaxis Experimental Patients will be administered an intermediate dose of low molecular weight heparin, choice of agent according to availability and local practice at the participating site. The maximum dose of enoxaparin will be 120 mg/d, tinzaparin 125 IU/kg/day (not available within Australia), and Dalteparin 15,000 IU/d. (Arm Closed) Anticoagulation - therapeutic anticoagulation Experimental 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 (Arm Never Opened) Antibody - Standard of Care No intervention No hyperimmune globulin (Arm Never Opened) Antibody - hyperimmune globulin Experimental 2 doses of 30mL (3x10mL vials) of COVID-19 Hyper-Immunoglobulin (Human) given over 2 days within 48 hours of randomisation Antiviral II - No antiviral agent No intervention Participants will receive no antiviral agents intended to be active against SARS-CoV-2 for 28 days or until hospital discharge, whichever occurs first. Antiviral II - Nirmatrelvir-ritonavir Experimental The dose of nirmatrelvir-ritonavir is dependent on renal function. Participants will receive 100mg BD oral/enteral Ritonavir and either 150mg BD (if eGFR 30-59 mL/min/1.73m2) or 300mg BD (eGFR \>= 60 mL/min/1.73m2) oral/enteral Nirmatrelvir. Investigators are advised to consider withholding treatment if the participant's eGFR \< 30 mL/min/1.73m2. Antiviral II - Remdisivir Experimental 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. Antiviral II - Nirmatrelvir-ritonavir + remdesivir Experimental Participants will receive both nirmatrelvir-ritonavir and remdesivir using the dose and administration methods described above. Treatment: Drugs: (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. Treatment: Drugs: (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. Treatment: Drugs: (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. Treatment: Drugs: (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). Treatment: Other: (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 Treatment: Drugs: 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. Treatment: Drugs: 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.
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Comparison

Control group Not available

Comparison not available.

Outcomes

Not Available