[Source: JAMA, full page: (LINK). Abstract, edited.]
Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support Among Critically Ill Patients With COVID-19 – A Randomized Clinical Trial
Pierre-François Dequin, MD, PhD1,2,3; Nicholas Heming, MD, PhD4,5; Ferhat Meziani, MD, PhD6,7; Gaëtan Plantefève, MD8; Guillaume Voiriot, MD, PhD9,10; Julio Badié, MD11; Bruno François, MD12,13,14; Cécile Aubron, MD, PhD15,16; Jean-Damien Ricard, MD, PhD17; Stephan Ehrmann, MD, PhD1,2,3; Youenn Jouan, MD, PhD1,2,3; Antoine Guillon, MD, PhD1,2,3; Marie Leclerc, MSc18; Carine Coffre, MSc18; Hélène Bourgoin, PharmD19; Céline Lengellé, PharmD20; Caroline Caille-Fénérol, MSc14; Elsa Tavernier, PhD3; Sarah Zohar, PhD21; Bruno Giraudeau, PhD3,22; Djillali Annane, MD, PhD4,5; Amélie Le Gouge, MSc3; for the CAPE COVID Trial Group and the CRICS-TriGGERSep Network
Author Affiliations: 1 Médecine Intensive-Réanimation, CHU de Tours, Tours, France; 2 INSERM U1100, Centre d’Etude des Pathologies Respiratoires, Université de Tours, Tours, France; 3 INSERM CIC1415, CHU de Tours, Tours, France; 4 Médecine Intensive Réanimation, Hôpital Raymond Poincaré (GHU APHP Université Paris Saclay), Garches, France, and RHU RECORDS and FHU SEPSIS; 5 INSERM U1173, Université de Versailles SQY-Université Paris Saclay, Garches, France; 6 Médecine Intensive Réanimation, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg, Strasbourg, France; 7 INSERM UMR 1260, Université de Strasbourg, Strasbourg, France; 8 Réanimation polyvalente, CH Victor Dupouy, Argenteuil, France; 9 Médecine Intensive Réanimation, Hôpital Tenon (Assistance Publique–Hôpitaux de Paris), Paris, France; 10 Sorbonne Université, Paris, France; 11 Réanimation Polyvalente, Hôpital Nord Franche-Comté, Trevenans, France; 12 Réanimation Polyvalente, CHU de Limoges, Limoges, France; 13 INSERM UMR 1092, Université de Limoges, Limoges, France; 14 INSERM CIC 1435, CHU de Limoges, Limoges, France; 15 Médecine Intensive Réanimation, CHRU de Brest, Brest, France; 16 Université de Bretagne Occidentale, Brest, France; 17 Université de Paris, IAME U1137, Médecine Intensive Réanimation, DMU ESPRIT, Hôpital Louis Mourier, Assistance Publique–Hôpitaux de Paris, Colombe, France; 18 Délégation à la Recherche Clinique et à l’Innovation, CHU de Tours, Tours, France; 19 Pharmacie à Usage Interne, CHU de Tours, Tours, France; 20 Centre régional de pharmacovigilance et d’information sur le médicament, service de pharmacosurveillance, CHU de Tours, Tours, France; 21 INSERM, Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, Paris, France; 22 Université de Tours, Université de Nantes, INSERM, SPHERE U1246, Tours, France
JAMA. Published online September 2, 2020. doi:10.1001/jama.2020.16761
Key Points
- Question – Does low-dose hydrocortisone decrease treatment failure in patients with COVID-19–related acute respiratory failure?
- Findings – In this randomized clinical trial that included 149 patients and was terminated early following the recommendation of the data and safety monitoring board, there was no significant difference in the rate of treatment failure (defined as death or persistent respiratory support with mechanical ventilation or high-flow oxygen therapy) on day 21 between the hydrocortisone and placebo groups (42.1% vs 50.7%, respectively).
- Meaning – Low-dose hydrocortisone did not significantly reduce treatment failure in patients with COVID-19–related acute respiratory failure; however, the study was stopped early and was therefore likely underpowered.
Abstract
Importance
Coronavirus disease 2019 (COVID-19) is associated with severe lung damage. Corticosteroids are a possible therapeutic option.
Objective
To determine the effect of hydrocortisone on treatment failure on day 21 in critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute respiratory failure.
Design, Setting, and Participants
Multicenter randomized double-blind sequential trial conducted in France, with interim analyses planned every 50 patients. Patients admitted to the intensive care unit (ICU) for COVID-19–related acute respiratory failure were enrolled from March 7 to June 1, 2020, with last follow-up on June 29, 2020. The study intended to enroll 290 patients but was stopped early following the recommendation of the data and safety monitoring board.
Interventions
Patients were randomized to receive low-dose hydrocortisone (n = 76) or placebo (n = 73).
Main Outcomes and Measures
The primary outcome, treatment failure on day 21, was defined as death or persistent dependency on mechanical ventilation or high-flow oxygen therapy. Prespecified secondary outcomes included the need for tracheal intubation (among patients not intubated at baseline); cumulative incidences (until day 21) of prone position sessions, extracorporeal membrane oxygenation, and inhaled nitric oxide; Pao2:Fio2 ratio measured daily from day 1 to day 7, then on days 14 and 21; and the proportion of patients with secondary infections during their ICU stay.
Results
The study was stopped after 149 patients (mean age, 62.2 years; 30.2% women; 81.2% mechanically ventilated) were enrolled. One hundred forty-eight patients (99.3%) completed the study, and there were 69 treatment failure events, including 11 deaths in the hydrocortisone group and 20 deaths in the placebo group. The primary outcome, treatment failure on day 21, occurred in 32 of 76 patients (42.1%) in the hydrocortisone group compared with 37 of 73 (50.7%) in the placebo group (difference of proportions, –8.6% [95.48% CI, –24.9% to 7.7%]; P = .29). Of the 4 prespecified secondary outcomes, none showed a significant difference. No serious adverse events were related to the study treatment.
Conclusions and Relevance
In this study of critically ill patients with COVID-19 and acute respiratory failure, low-dose hydrocortisone, compared with placebo, did not significantly reduce treatment failure (defined as death or persistent respiratory support) at day 21. However, the study was stopped early and likely was underpowered to find a statistically and clinically important difference in the primary outcome.
Trial Registration ClinicalTrials.gov Identifier: NCT02517489
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Keywords: SARS-CoV-2; COVID-19; Corticosteroids; Intensive Care.
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