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Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.
Angus, Derek C; Derde, Lennie; Al-Beidh, Farah; Annane, Djillali; Arabi, Yaseen; Beane, Abigail; van Bentum-Puijk, Wilma; Berry, Lindsay; Bhimani, Zahra; Bonten, Marc; Bradbury, Charlotte; Brunkhorst, Frank; Buxton, Meredith; Buzgau, Adrian; Cheng, Allen C; de Jong, Menno; Detry, Michelle; Estcourt, Lise; Fitzgerald, Mark; Goossens, Herman; Green, Cameron; Haniffa, Rashan; Higgins, Alisa M; Horvat, Christopher; Hullegie, Sebastiaan J; Kruger, Peter; Lamontagne, Francois; Lawler, Patrick R; Linstrum, Kelsey; Litton, Edward; Lorenzi, Elizabeth; Marshall, John; McAuley, Daniel; McGlothin, Anna; McGuinness, Shay; McVerry, Bryan; Montgomery, Stephanie; Mouncey, Paul; Murthy, Srinivas; Nichol, Alistair; Parke, Rachael; Parker, Jane; Rowan, Kathryn; Sanil, Ashish; Santos, Marlene; Saunders, Christina; Seymour, Christopher; Turner, Anne; van de Veerdonk, Frank; Venkatesh, Balasubramanian.
  • Angus DC; The Clinical Research Investigation and Systems Modeling of Acute Illness (CRISMA) Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
  • Derde L; The UPMC Health System Office of Healthcare Innovation, Pittsburgh, Pennsylvania.
  • Al-Beidh F; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
  • Annane D; Intensive Care Center, University Medical Center Utrecht, Utrecht, the Netherlands.
  • Arabi Y; Division of Anaesthetics, Pain Medicine and Intensive Care Medicine, Department of Surgery and Cancer, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom.
  • Beane A; Intensive Care Unit, Raymond Poincaré Hospital (AP-HP), Paris, France.
  • van Bentum-Puijk W; Simone Veil School of Medicine, University of Versailles, Versailles, France.
  • Berry L; University Paris Saclay, Garches, France.
  • Bhimani Z; Intensive Care Department, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
  • Bonten M; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
  • Bradbury C; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
  • Brunkhorst F; Berry Consultants LLC, Austin, Texas.
  • Buxton M; Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada.
  • Buzgau A; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
  • Cheng AC; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.
  • de Jong M; Bristol Royal Informatory, Bristol, United Kingdom.
  • Detry M; University of Bristol, Bristol, United Kingdom.
  • Estcourt L; Center for Clinical Studies and Center for Sepsis Control and Care (CSCC), Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany.
  • Fitzgerald M; Global Coalition for Adaptive Research, San Francisco, California.
  • Goossens H; Helix, Monash University, Melbourne, Victoria, Australia.
  • Green C; Infection Prevention and Healthcare Epidemiology Unit, Alfred Health, Melbourne, Victoria, Australia.
  • Haniffa R; Australian and New Zealand Intensive Care Research Centre, School of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
  • Higgins AM; Department of Medical Microbiology, Amsterdam University Medical Center, University of Amsterdam, the Netherlands.
  • Horvat C; Berry Consultants LLC, Austin, Texas.
  • Hullegie SJ; NHS Blood and Transplant, Bristol, United Kingdom.
  • Kruger P; Transfusion Medicine, Medical Sciences Division, University of Oxford, Oxford, United Kingdom.
  • Lamontagne F; Berry Consultants LLC, Austin, Texas.
  • Lawler PR; Department of Microbiology, Antwerp University Hospital, Antwerp, Belgium.
  • Linstrum K; Australian and New Zealand Intensive Care Research Centre, School of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
  • Litton E; Network for Improving Critical Care Systems and Training, Colombo, Sri Lanka.
  • Lorenzi E; Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand.
  • Marshall J; Australian and New Zealand Intensive Care Research Centre, School of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
  • McAuley D; The Clinical Research Investigation and Systems Modeling of Acute Illness (CRISMA) Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
  • McGlothin A; The UPMC Health System Office of Healthcare Innovation, Pittsburgh, Pennsylvania.
  • McGuinness S; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
  • McVerry B; Intensive Care Unit, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
  • Montgomery S; Université de Sherbrooke, Sherbrooke, Quebec, Canada.
  • Mouncey P; Cardiac Intensive Care Unit, Peter Munk Cardiac Centre, University Health Network, Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada.
  • Murthy S; The Clinical Research Investigation and Systems Modeling of Acute Illness (CRISMA) Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
  • Nichol A; School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia.
  • Parke R; Berry Consultants LLC, Austin, Texas.
  • Parker J; Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada.
  • Rowan K; Interdepartmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada.
  • Sanil A; Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, United Kingdom.
  • Santos M; Berry Consultants LLC, Austin, Texas.
  • Saunders C; Australian and New Zealand Intensive Care Research Centre, School of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
  • Seymour C; Cardiothoracic and Vascular Intensive Care Unit, Auckland City Hospital, Auckland, New Zealand.
  • Turner A; The Health Research Council of New Zealand, Wellington, New Zealand.
  • van de Veerdonk F; Medical Research Institute of New Zealand, Wellington, New Zealand.
  • Venkatesh B; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
JAMA ; 324(13): 1317-1329, 2020 10 06.
Article in English | MEDLINE | ID: covidwho-739603
Semantic information from SemMedBD (by NLM)
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ABSTRACT
Importance Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited.

Objective:

To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and

Participants:

An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020.

Interventions:

The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and

Measures:

The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%).

Results:

After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration ClinicalTrials.gov Identifier NCT02735707.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Respiration, Artificial / Hydrocortisone / Coronavirus Infections / Anti-Inflammatory Agents Type of study: Controlled clinical trial / Etiology study / Prognostic study / Randomized controlled trials Limits: Adult / Female / Humans / Male / Middle aged Language: English Journal: JAMA Year: 2020 Document Type: Article

Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Respiration, Artificial / Hydrocortisone / Coronavirus Infections / Anti-Inflammatory Agents Type of study: Controlled clinical trial / Etiology study / Prognostic study / Randomized controlled trials Limits: Adult / Female / Humans / Male / Middle aged Language: English Journal: JAMA Year: 2020 Document Type: Article