Covid-19 Living Data

Trial NCT02735707
Publication Angus DC, JAMA, 2020 (published paper)
Dates: 2020-03-09 to 2020-06-17
Funding: Public/non profit (Platform for European Preparedness Against (Re-) emerging Epidemics (PREPARE) consortium by the European Union, FP7-HEALTH-2013-INNOVATION-1, the Australian National Health and Medical Research Council, the New Zealand H)
Conflict of interest: Yes

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / Australia, Canada, France, Ireland, Netherlands, New Zealand, UK, USA Follow-up duration (days): 21
Inclusion criteria	Patients aged 18 years or older with presumed or confirmed SARS-CoV-2 infection who were admitted to an intensive care unit (ICU) for provision of respiratory or cardiovascular organ support were classified as severe and eligible for enrollment in the COVID-19 corticosteroid domain. An ICU could include an area of the hospital repurposed to function as an ICU for surge capacity management. Respiratory organ support was defined as invasive or noninvasive mechanical ventilation or high-flow nasal cannula if the flow rate was 30 L/minor greater and fraction of inspired oxygen of 0.4 or greater. Cardiovascular organ support was defined as the intravenous infusion of any vasopressor or inotrope.
Exclusion criteria	Report: Presumption that death is imminent with lack of commitment to full support and participation in the trial in the prior 90 days. Additional exclusion criteria for the corticosteroid domain included known hypersensitivity to hydrocortisone, systemic corticosteroid use, and more than 36 hours elapsed since ICU admission. Protocol (additional criteria): Patient has been randomized in a trial evaluating corticosteroids, where the protocol of that trial requires ongoing administration of study drug The treating clinician believes that participation in the domain would not be in the best interests of the patient
Interventions
	Treatment Fixed-dose hydrocortisone 50 mg IV infusion every 6 hours for 7 days
	Control Standard care Definition of Standard care: No hydrocortisone (or other corticosteroid) use. Other aspects of care were provided as per each site's standard of care.
Participants
	Randomized 251 participants (n₁=143 / n₂= 108)
	Characteristics of participants N=251 Mean age : 60.2 170 males Severity : Mild: n=0 / Moderate: n=0/ Severe: n=98 Critical: n=140
Primary outcome
	In the register All-cause mortality [ Time Frame: Day 90 ] Days alive and not receiving organ support in ICU [ Time Frame: Day 21 ]
	In the report Respiratory and cardiovascular organ support-free days up to day 21, an ordinal end point with death within the hospital as the worst outcome (labeled -1), then the length of time free of both respiratory and cardiovascular organ support, such that the best outcome would be 21 organ support–free days.
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing stated Yes
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to all available versions of the published article, the study registry, supplementary documents and protocol were used in data extraction and risk of bias assessment. The study was terminated early. As a result, the target sample size specified in the registry was not achieved. Quote: "Following a press release from the RECOVERY trial on June 16, 2020, and in response to discussions held across the participating sites, the blinded international trial steering committee decided on June 17, 2020, to stop enrollment of patients with COVID-19 in the corticosteroid domain due to a loss of equipoise." There is no change from the trial registration in the intervention and control treatments. Outcome time points differ between the registry and the report but this could be due to the early termination. 'All cause mortality' is presented as the primary outcome in the registry and as secondary in the report.