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September - 2020


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Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support Among Critically Ill Patients With COVID-19

PF Dequin, N Heming, F Meziani, et al or the CAPE COVID Trial Group and the CRICS-TriGGERSep Network JAMA, 2020, online Sept 2020


There is a lot to review regarding corticosteroids and COVID-19;

This trial was embedded in the CAPE COVID Trial - to determine the superiority of low-dose hydrocortisone compared with placebo in reducing mortality on day 28 in ICU patients with community-acquired pneumonia. A COVID-19 group was added. 


  • Statistical plan
    • Assumed 30% primary outcome (treatment failure day 21), test the superiority go HC vs placebo with assumed event rate 15% in HC arm, 80% power, 5% type I error, required 260 participants
    • Trial stopped at 149/260 participants following the RECOVERY result publication 
  • 149 adults with acute respiratory failure, admitted 9 participating French ICUs, and suspected or confirmed COVID-19
  • Commence within 24hrs onset of severity criteria;
    • MV with PEEP >5cmH2O
    • PF <300 with FiO2 >50% on high flow O2 or reservoir mask
    • PSI (pulmonary severity index) >130
  • Intervention
    • Hydrocortisone 200mg/d 7-days, 100mg/d 4 days, 50 mg/d 3 days (total 14 days). This was shortened to total 8-days if improved by day 4
    • Placebo 
  • Baseline: Mean age 62 yrs, 97% PCR +, duration of symptoms prior randomisation 9-10 days, 81% MV at enrolment 
  • Treatment: Mean study treatment 11 days HC vs 13 days placebo 
  • Primary outcome: 
    • Death or persistent dependency on mechanical ventilation or high-flow oxygen therapy. 
    • 42% HC vs 51% placebo, diff -8.6%, 95% CI -25% to 8%, p=0.29)
  • Secondary outcome: 
    • No difference tracheal intubation, prone, ECMO, iNO, daily P:F 
    • Day 21 Death 14.7% vs 27.4%, diff -12.7% (-25.7 to 0.3%, p=0.06)

Overall the CAPE COVID Trial reported use of hydrocortisone did not significantly reduce the rate of treatment failure (death, MV, HFO) compared to placebo in critically ill adults with COVID-19. The trial was stopped prematurely due to RECOVERY, the post-hoc analysis of mortality at D21 was not significant but was consistent with RECOVERY. 



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.


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