High-Dose Dexamethasone and Oxygen Support Strategies in Intensive Care Unit Patients With Severe COVID-19 Acute Hypoxemic Respiratory Failure
Lila Bouadma, Armand Mekontso Dessap, Charles Burdet, Hamid Merdji, Julien Poissy, Claire Dupuis, Christophe Guitton, Carole Schwebel, Yves Cohen, Cédric Bruel, Mehdi Marzouk, Guillaume Géri, Charles Cerf, Bruno Mégarbane, Pierre Garçon, Éric Kipnis, Benoît Visseaux, Naima Beldjoudi, Sylvie Chevret, Jean‐François Timsit, COVIDICUS Study Group, Naima Beldjoudi, Sylvie Chevret, Charles Burdet, Céline Alloux, Fadila Amerali, Béatrice Andriss, Kamyl Baghli, Hélène Brocvielle, Florence Capelle, Ines Chibane, Sarra Dalibey, Nadia Ettalhaoui, Sabrine Lamri, Yohan Maurer, Jean-Marc Mintsa, Alice Oubahim, Marie-Capucine Tellier, Imane Zemihi, Lila Bouadma, Moustafa Abdel-Nabey, Billal Azzouguen, Ghenima Belkessa, Étienne de Montmollin, Veronique Deiler, Claire Dupuis, Aline Fallet, Guillaume Franchineau, Tiphaine Girard, Alexandra Grinea, Pierre Jaquet, Laura D. Kramer, Fariza Lamara, Lucie Lefèvre, Mehdi Marzouk, Juliette Patrier, Simona Presente, Faiza Sayagh, Fabrice Sinnah, Romain Sonneville, Paul-Henri Wicky, Sylia Zmihi, Yves Cohen, Nathalie Barget, Rawan Belmokhtar, Sabrina Brahmi, Naoual Djabra, Nathan Ebstein, Souha Fliss, Amina Gourbdji, William Juguet, Fadhila Messani, Thomas Rambaud, Vanessa Rathouin, Mani Rebai, Marthe Rigal, Julien Schmidt, Marie Soulié, Yacine Tandjaoui-Lombiotte, Anaïs Winchenne, Marianne Ziol, Romain Arrestier, François Bagate, Morgan Benais, Inès Bendib, LE Lan, Brice Benelli, Enora Berti, Astrid Bertier, Guillaume Carteaux, Muriel Carvalho, Pedro Cavaleiro, Nicolas Deprost, Otto Hartman, Anne-Fleur Haudebourg, Delphine Le Febvre De Nailly, Julien Lopinto, Sabrina Mahiou, Paul Masi, Gaël Michaud
Abstract
Importance: The benefit of high-dose dexamethasone and oxygenation strategies vs standard of care for patients with severe acute hypoxemic respiratory failure (AHRF) caused by COVID-19 pneumonia is debated. Objectives: To assess the benefit of high-dose dexamethasone compared with standard of care dexamethasone, and to assess the benefit of high-flow nasal oxygen (HFNo2) or continuous positive airway pressure (CPAP) compared with oxygen support standard of care (o2SC). Design, Setting, and Participants: This multicenter, placebo-controlled randomized clinical trial was conducted in 19 intensive care units (ICUs) in France from April 2020 to January 2021. Eligible patients were consecutive ICU-admitted adults with COVID-19 AHRF. Randomization used a 2 × 3 factorial design for dexamethasone and oxygenation strategies; patients not eligible for at least 1 oxygenation strategy and/or already receiving invasive mechanical ventilation (IMV) were only randomized for dexamethasone. All patients were followed-up for 60 days. Data were analyzed from May 26 to July 31, 2021. Interventions: Patients received standard dexamethasone (dexamethasone-phosphate 6 mg/d for 10 days [or placebo prior to RECOVERY trial results communication]) or high-dose dexamethasone (dexamethasone-phosphate 20 mg/d on days 1-5 then 10 mg/d on days 6-10). Those not requiring IMV were additionally randomized to o2SC, CPAP, or HFNo2. Main Outcomes and Measures: The main outcomes were time to all-cause mortality, assessed at day 60, for the dexamethasone interventions, and time to IMV requirement, assessed at day 28, for the oxygenation interventions. Differences between intervention groups were calculated using proportional Cox models and expressed as hazard ratios (HRs). Results: Among 841 screened patients, 546 patients (median [IQR] age, 67.4 [59.3-73.1] years; 414 [75.8%] men) were randomized between standard dexamethasone (276 patients, including 37 patients who received placebo) or high-dose dexamethasone (270 patients). Of these, 333 patients were randomized among o2SC (109 patients, including 56 receiving standard dexamethasone), CPAP (109 patients, including 57 receiving standard dexamethasone), and HFNo2 (115 patients, including 56 receiving standard dexamethasone). There was no difference in 60-day mortality between standard and high-dose dexamethasone groups (HR, 0.96 [95% CI, 0.69-1.33]; P = .79). There was no significant difference for the cumulative incidence of IMV criteria at day 28 among o2 support groups (o2SC vs CPAP: HR, 1.08 [95% CI, 0.71-1.63]; o2SC vs HFNo2: HR, 1.04 [95% CI, 0.69-1.55]) or 60-day mortality (o2SC vs CPAP: HR, 0.97 [95% CI, 0.58-1.61; o2SC vs HFNo2: HR, 0.89 [95% CI, 0.53-1.47]). Interactions between interventions were not significant. Conclusions and Relevance: In this randomized clinical trial among ICU patients with COVID-19-related AHRF, high-dose dexamethasone did not significantly improve 60-day survival. The oxygenation strategies in patients who were not initially receiving IMV did not significantly modify 28-day risk of IMV requirement. Trial Registration: ClinicalTrials.gov Identifier: NCT04344730; EudraCT: 2020-001457-43.