Covid-19 Living Data

Trial NCT02517489
Publication Dequin P-F, JAMA (2020) (published paper)
Dates: 2020-03-07 to 2020-06-01
Funding: Public/non profit (French Ministry of Health, Programme Hospitalier de Recherche Clinique (PHRC))
Conflict of interest: Yes

Methods
	RCT Blinding: double blinding
	Location : Multicenter / France Follow-up duration (days): 28
Inclusion criteria	Patients aged at least 18 years admitted to 1 of the 9 participating French ICUs for acute respiratory failure could be included if they had a biologically confirmed (reverse transcriptase-polymerase chain reaction) or suspected (suggestive chest computed tomography scan result in the absence of any other cause of pneumonia) COVID-19. The experimental treatment had to be administered within 24 hours of the onset of the first severity criterion (see below) or within 48 hours for patients referred from another hospital. One of 4 severity criteria had to be present: need for mechanical ventilation with a positive end-expiratory pressure (PEEP) of 5 cm H20 or more a ratio of Pao2 to fraction of inspired oxygen (Fio2) less than 300 on high-flow oxygen therapy with an Fio2 value of at least 50% for patients receiving oxygen through a reservoir mask, a Pao2:Fio2 ratio less than 300, estimated using prespecified charts or a Pulmonary Severity Index greater than 130. Patients receiving vasopressors to correct hypotension related to sedative drugs and mechanical ventilation at high PEEP levels could be included.
Exclusion criteria	Report: septic shock and do-not-intubate orders Protocol and Registry: •Patient treated by vasopressors for septic shock at the time of inclusion •Clinical history suggesting of aspiration of gastric content •Patient treated by invasive mechanical ventilation within 14 days before current hospital admission •Patient treated by antibiotics for a respiratory infection for more than seven days at the admission to the hospital (except if a pathogen resistant to this antibiotics is isolated) •History of cystic fibrosis •Post-obstructive pneumonia •Patients in which rapid PCR-test is positive for flu •Active tuberculosis or fungal infection •Active viral hepatitis or active infection with herpes viruses •Myelosuppression •Decision of withholding mechanical ventilation or endotracheal intubation •Hypersensitivity to corticosteroids •Patient needing anti-inflammatory corticosteroids or substitutive hydrocortisone for any reason •Patients under treatment by more than 15 mg/d of prednisone (or equivalent) for more than 30 days •Patient already enrolled in another drug trial with mortality as an end-point. If the patient is already participating in another therapeutic trial with a different endpoint, the investigator must verify that inclusion in CAPE COD can not prejudice it. •Pregnant or breastfeeding woman •Patient on judicial protection
Interventions
	Treatment Hydrocortisone 200 mg IV infusion once a day for 7 days, then 100 mg once a day for 4 days, followed by 50 mg once a day for 3 days.
	Control Placebo
Participants
	Randomized participants : Hydrocortisone=76 Placebo=73
	Characteristics of participants N= 149 Mean age : NR 104 males Severity : Mild: n=0 / Moderate: n=0 / Severe: n=28 Critical: n=121 Number of vaccinated participants: NR
Primary outcome
	In the register Day 28 all causes mortality [ Time Frame: at day 28 ] Day 21 failure [ Time Frame: at day 21 ]
	In the report Treatment failure on day 21
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication:
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, protocol and statistical analysis plan were used in data extraction and risk of bias assessment. The study was terminated early considering that it would be unethical to resume a corticosteroid vs placebo trial. As a result, the target sample size (290) was not achieved. Quote: "On June 30, 2020, the DSMB recommended suspension of inclusions pending publication of the results of the RECOVERY trial and possible changes in treatment recommendations. The sponsor decided to discontinue the study on July 3, 2020, considering that it would be unethical to resume a corticosteroid vs placebo trial". There is no change from the trial registration in the intervention and control treatments nor the primary outcome. Some secondary outcomes in the registry are not present in the report (All-causes mortality at day 90, SF-36 Health Survey at day 90, Weight-gain at baseline and day 7, Biomarkers: procalcitonin at baseline, day 3 and day 7,C-reactive protein at baseline, day 3 and day 7 ,plasmatic concentration of pro-inflammatory cytokines (IL-6, IL-20, IL-22, IL-22BP, HBD2, TNF) at baseline, day 3 and day 7) This trial was embedded in the ongoing Community- Acquired Pneumonia:Evaluation of Corticosteroids(CAPE-COD) trial.