Glucocorticoid Therapy for COVID-19 Critically Ill Patients With Severe Acute Respiratory Failure

Glucocorticoid Therapy for Critically Ill Patients With Severe Acute Respiratory Infections Caused by COVID-19: a Prospective, Randomized Controlled Trial

In this multi-center, randomized, control study, the investigators will evaluate the efficacy and safety of glucocorticoid in combination with standard care for COVID-19 patents with Severe acute respiratory failure.

Study Overview

• Status: Completed
• Conditions: COVID-19 Infections
• Intervention / Treatment: Other: Standard care; Drug: methylprednisolone therapy

Detailed Description

COVID-19 is a novel coronavirus that was initially outbreak in Wuhan, China. Severe acute respiratory infection with COVID-19 causes severe acute respiratory failure with substantial mortality. Currently, the standard care is supportive care, and no treatment is proven to be effective for this condition.

Glucocorticoid therapy is widely used among critically ill patients with other coronavirus infection such as SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome). However, whether glucocorticoid improved the outcome of COVID-19 remains unknown. We hypothesized that glucocorticoid would improve the prognosis of patietns with COVID-19.

In this study, critically ill patients with COVID-19 were enrolled and randomized to receive ether standard care or standard care in combination with methylprednisolone therapy. The primary outcome is the difference of Murray lung injury score between two groups.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 010
      • Medical ICU,Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult
• PCR confirmed COVID-19 infection
• Symptoms developed more than 7 days
• PaO2/FiO2 < 200 mmHg
• Positive pressure ventilation (non-invasive or invasive) or high flow nasal cannula (HFNC) higher than 45 L/min for less than 48 hours
• Requiring ICU admission

Exclusion Criteria:

• pregnancy;
• patients currently taking corticosteroids (cumulative 400 mg prednisone or equivalent);
• Severe underlying disease, i.e. end stage of malignancy disease or end stage of pulmonary disease;
• Severe adverse events before ICU admission, i.e. cardiac arrest;
• Underlying disease requiring corticosteroids;
• Contraindication for corticosteroids;
• Recruited in other clinical intervention trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: standard care	Other: Standard care; Standard care
Experimental: standard care + methylprednisolone therapy; Methylprednisolone 40 mg q12h for 5 days	Drug: methylprednisolone therapy; Methylprednisolone 40 mg q12h for 5 days; Other Names: Steroids

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lower Murray lung injury score	Murray lung injury score decreased more than one point means better outcome.The Murray scoring system range from 0 to 4 according to the severity of the condition.	7 days after randomization
Lower Murray lung injury score	Murray lung injury score decreased more than one point means better outcome.The Murray scoring system range from 0 to 4 according to the severity of the condition.	14 days after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The difference of PaO2/FiO2 between two groups	PaO2/FiO2 denotes ratio of arterial partial pressure of O2 and the fraction of inspired oxygen, with a higher PaO2/FiO2 means favorable outcome.	7 days after randomization
Lower Sequential Organ Failure Assessment (SOFA) score	Lower SOFA score means better outcome. The SOFA score system range from 0 to 24 according to the severity of the condition.	7 days after randomization
Mechanical ventilation support	Percentage of patients requiring Mechanical ventilation support	7 days after randomization
The difference of PaO2/FiO2 between two groups	PaO2/FiO2 denotes ratio of arterial partial pressure of O2 and the fraction of inspired oxygen, with a higher PaO2/FiO2 means favorable outcome.	14 days after randomization
Lower Sequential Organ Failure Assessment (SOFA) score	Lower SOFA score means better outcome. The SOFA score system range from 0 to 24 according to the severity of the condition.	14 days after randomization
Mechanical ventilation support	Percentage of patients requiring Mechanical ventilation support	14 days after randomization
Clearance of noval coronavirus	Clearance of noval coronavirus in upper respiratory tract or lower respiratory tract	14 days after randomization
All-cause mortality	All-cause mortality	30 days after randomization

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: Zhongnan Hospital; Renmin Hospital of Wuhan University; Zhongda Hospital

Publications and helpful links

General Publications

• Arabi YM, Mandourah Y, Al-Hameed F, Sindi AA, Almekhlafi GA, Hussein MA, Jose J, Pinto R, Al-Omari A, Kharaba A, Almotairi A, Al Khatib K, Alraddadi B, Shalhoub S, Abdulmomen A, Qushmaq I, Mady A, Solaiman O, Al-Aithan AM, Al-Raddadi R, Ragab A, Balkhy HH, Al Harthy A, Deeb AM, Al Mutairi H, Al-Dawood A, Merson L, Hayden FG, Fowler RA; Saudi Critical Care Trial Group. Corticosteroid Therapy for Critically Ill Patients with Middle East Respiratory Syndrome. Am J Respir Crit Care Med. 2018 Mar 15;197(6):757-767. doi: 10.1164/rccm.201706-1172OC.
• Auyeung TW, Lee JS, Lai WK, Choi CH, Lee HK, Lee JS, Li PC, Lok KH, Ng YY, Wong WM, Yeung YM. The use of corticosteroid as treatment in SARS was associated with adverse outcomes: a retrospective cohort study. J Infect. 2005 Aug;51(2):98-102. doi: 10.1016/j.jinf.2004.09.008.
• Raghavendran K, Napolitano LM. Definition of ALI/ARDS. Crit Care Clin. 2011 Jul;27(3):429-37. doi: 10.1016/j.ccc.2011.05.006.
• Vincent JL, de Mendonca A, Cantraine F, Moreno R, Takala J, Suter PM, Sprung CL, Colardyn F, Blecher S. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine. Crit Care Med. 1998 Nov;26(11):1793-800. doi: 10.1097/00003246-199811000-00016.
• Sultana J, Crisafulli S, Gabbay F, Lynn E, Shakir S, Trifiro G. Challenges for Drug Repurposing in the COVID-19 Pandemic Era. Front Pharmacol. 2020 Nov 6;11:588654. doi: 10.3389/fphar.2020.588654. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2020
• Primary Completion (Actual): April 13, 2020
• Study Completion (Actual): April 13, 2020

Study Registration Dates

• First Submitted: January 23, 2020
• First Submitted That Met QC Criteria: January 25, 2020
• First Posted (Actual): January 28, 2020

Study Record Updates

• Last Update Posted (Actual): June 16, 2020
• Last Update Submitted That Met QC Criteria: June 13, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Infections; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: Glucocorticoid COVID-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No