Clinical trial NCT04244591: Glucocorticoid Therapy for COVID-19 Critically Ill Patients With Severe Acute Respiratory Failure
Official title: Glucocorticoid Therapy for Critically Ill Patients With Severe Acute Respiratory Infections Caused by COVID-19: a Prospective, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: COVID-19 Infections
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Zhongda Hospital
name: Zhongnan Hospital
name: Renmin Hospital of Wuhan University
First posted: 2020-01-28
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Lower Murray lung injury score
timeFrame: 7 days after randomization
measure: Lower Murray lung injury score
timeFrame: 14 days after randomization
Secondary outcomes:
measure: The difference of PaO2/FiO2 between two groups
timeFrame: 7 days after randomization
measure: Lower Sequential Organ Failure Assessment (SOFA) score
timeFrame: 7 days after randomization
measure: Mechanical ventilation support
timeFrame: 7 days after randomization
measure: The difference of PaO2/FiO2 between two groups
timeFrame: 14 days after randomization
measure: Lower Sequential Organ Failure Assessment (SOFA) score
timeFrame: 14 days after randomization
measure: Mechanical ventilation support
timeFrame: 14 days after randomization
measure: Clearance of noval coronavirus
timeFrame: 14 days after randomization
measure: All-cause mortality
timeFrame: 30 days after randomization
Other outcomes:
Locations:
city: Beijing
country: China
facility: Medical ICU,Peking Union Medical College Hospital
state: Beijing
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.