Study: NCT02735707

Intervention type: DRUG
Group type: OTHER
Intervention: Ceftriaxone
Description: The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice.

Intervention type: DRUG
Group type: OTHER
Intervention: Moxifloxacin or Levofloxacin
Description: The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice.

Intervention type: DRUG
Group type: OTHER
Intervention: Piperacillin-tazobactam
Description: The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice.

Intervention type: DRUG
Group type: OTHER
Intervention: Ceftaroline
Description: The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice.~Note: this intervention is now closed.

Intervention type: DRUG
Group type: OTHER
Intervention: Amoxicillin-clavulanate
Description: The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice.

Intervention type: DRUG
Group type: OTHER
Intervention: Standard course macrolide
Description: Standard course of macrolide therapy, discontinued between study day 3 and the end of study day 5.~The dosing of and route of administration is not protocolised, the following guidance is provided:~* Initial IV administration of a macrolide is strongly preferred~* The preferred IV macrolide is azithromycin, but IV clarithromycin may be substituted.~* The preferred enteral macrolide is azithromycin, but enteral clarithromycin or roxithromycin may be substituted.

Intervention type: DRUG
Group type: OTHER
Intervention: Extended course macrolide
Description: Extended course of macrolide therapy discontinued at the end of study day 14 or hospital discharge (whichever occurs first).~The dosing of and route of administration is not protocolised, the following guidance is provided:~* Initial IV administration of a macrolide is strongly preferred~* The preferred IV macrolide is azithromycin, but IV clarithromycin may be substituted.~* The preferred enteral macrolide is azithromycin, but enteral clarithromycin or roxithromycin may be substituted.

Intervention type: OTHER
Group type: OTHER
Intervention: No systemic corticosteroid
Description: Patients are not to receive any systemic corticosteroids, including hydrocortisone, to study day 28 or hospital discharge (whichever occurs first).

Intervention type: DRUG
Group type: OTHER
Intervention: Fixed-duration Hydrocortisone
Description: 50mg of intravenous hydrocortisone will be administered every 6 hours for up to 7 days.~Note: this intervention is now closed.

Intervention type: DRUG
Group type: OTHER
Intervention: Shock-dependent hydrocortisone
Description: 50mg IV hydrocortisone every 6 hours while the patient is in septic shock

Intervention type: DRUG
Group type: OTHER
Intervention: Fixed-duration higher dose Hydrocortisone
Description: 100mg of intravenous hydrocortisone will be administered every 6 hours for up to 7 days.~Note: this intervention was only available to patients with suspected or proven COVID-19 and is now closed.

Intervention type: OTHER
Group type: OTHER
Intervention: No antiviral agent for influenza
Description: No antiviral agent intended to be active against influenza infection is to be administered

Intervention type: DRUG
Group type: OTHER
Intervention: Five-days oseltamivir
Description: Oseltamivir administered enterally twice daily for 5 days or until hospital discharge (whichever occurs first)

Intervention type: DRUG
Group type: OTHER
Intervention: Ten-days oseltamivir
Description: Oseltamivir administered enterally twice daily for 10 days or until hospital discharge (whichever occurs first)

Intervention type: OTHER
Group type: OTHER
Intervention: No antiviral agent for COVID-19
Description: No antiviral agent intended to be active against SARS-CoV-2 infection is to be administered

Intervention type: DRUG
Group type: OTHER
Intervention: Lopinavir / Ritonavir
Description: Lopinavir/ritonavir 400/100mg administered enterally, or 5ml 80/20mg per mL solution suspension via gastric tube, every 12 hours. Administered for a minimum of 5 days, including if discharged from ICU prior to end of study day 5. For patients discharged from ICU between study day 6 and study day 14, lopinavir/ritonavir is ceased at ICU discharge. Lopinavir/ritonavir is ceased at the end of study day 14 if the patient remains in ICU.~Note: this intervention is now closed.

Intervention type: DRUG
Group type: OTHER
Intervention: Hydroxychloroquine
Description: Loading dose of 800mg hydroxychloroquine administered enterally every 6 hours until 2 doses have been administered. Subsequently, 400mg hydroxychloroquine will be administered enterally every 12 hours for 12 doses or ICU discharge (whichever occurs first).~Note: this intervention is now closed.

Intervention type: DRUG
Group type: OTHER
Intervention: Hydroxychloroquine + lopinavir/ritonavir
Description: Lopinavir/ritonavir 400/100mg administered enterally, or 5ml 80/20mg per mL solution suspension via gastric tube, every 12 hours. Administered for a minimum of 5 days, including if discharged from ICU prior to end of study day 5. For patients discharged from ICU between study day 6 and study day 14, lopinavir/ritonavir is ceased at ICU discharge. Lopinavir/ritonavir is ceased at the end of study day 14 if the patient remains in ICU.~Loading dose of 800mg hydroxychloroquine administered enterally every 6 hours until 2 doses have been administered. Subsequently, 400mg hydroxychloroquine will be administered enterally every 12 hours for 12 doses or ICU discharge (whichever occurs first).~Note: this intervention is now closed.

Intervention type: DRUG
Group type: OTHER
Intervention: Ivermectin
Description: Ivermectin administered enterally at a dose of 0.2 mg/kg once daily with a maximum daily dose of 24mg/day.~Note: this intervention is now closed.

Intervention type: OTHER
Group type: OTHER
Intervention: No immune modulation for COVID-19
Description: No immune modulating agent intended to be active against COVID-19 is to be administered.~Note: this intervention is now closed.

Intervention type: OTHER
Group type: OTHER
Intervention: No immune modulation for COVID-19
Description: No immune modulating agent intended to be active against COVID-19 is to be administered.~Note: this intervention is now closed.

Intervention type: DRUG
Group type: OTHER
Intervention: Interferon beta-1a
Description: IFN-β1a 10 μg will be administered as an intravenous bolus injection via a central or peripheral line. IFN-β1a will be administered once daily for 6 days or until ICU discharge, whichever occurs first.~Note: this intervention is now closed.

Intervention type: DRUG
Group type: OTHER
Intervention: Anakinra
Description: A loading dose of 300mg anakinra will be administered as a bolus via central or peripheral line. This is followed by maintenance doses of 100mg of anakinra administered every 6 hours.~In patients with renal impairment, anakinra will be administered on alternate days.~Note: this intervention is now closed.

Intervention type: DRUG
Group type: OTHER
Intervention: Tocilizumab
Description: Tocilizumab will be administered as a single dose of 8mg/kg estimated or measured body weight, with a maximum total dose of 800mg.~Tocilizumab will be administered as an IV infusion via central or peripheral line over a one-hour period.~Note: this intervention is now closed.

Intervention type: DRUG
Group type: OTHER
Intervention: Sarilumab
Description: Sarilumab will be administered as a single dose of 400mg, via IV infusion through peripheral or central line over a one-hour period.~Note: this intervention is now closed.