meta|Evidence - COVID-19
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dexamethasone (n=25) vs. standard of care (n=25)
randomized controlled trial some concerns about risk of bias
Dexamethasone
intravenous dexamethasone at a dose of 20 mg/day from day 1–5 and then at 10 mg/day from day 6–10.
Control
No corticosteroids
Patients in both groups received oxygen support (CPAP with pressure of 5–10 cmH2O and FIO2 equal to 60 to achieve SPO2≥90% and the duration was different ac-cording to the monitoring of patients’ clinical status), fluid support, and lopinavir/ritonavir (200/50 mg, two tablets twice a day) according to the National Iranian Guidelines
COVID-19 severe or critically
(1) age >18 years; (2) SARS-CoV-2 infection confirmed by a reverse transcription-polymerase chain reac-tion test; (3) ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen (PaO2/FiO2) between 100 and 300 mmHg; (4) bilateral lung infiltration; and (5) provision of written informed consent by the patient.
Open-label.
Single center, Dr. Masih Daneshvari Hospital, Tehran, Iran.
dexamethasone (n=151) vs. standard of care (n=148)
randomized controlled trial some concerns about risk of bias
Dexamethasone
Dexamethasone 20mg intravenously once daily for 5 days, followed by 10 mg intravenously once daily for additional 5 days or until ICU discharge, whichever occurred first, plus standard care.
Standard care
Standard care alone.
Standard care in both groups. All clinical interventions, such as use of antibiotics, ventilatory strategy, laboratory testing, and hemodynamic management were left at thediscretion of the ICU team for both groups.
COVID-19 severe or critically
Patients age ≥18 years old, with probable or confirmed infection by SARS-CoV2, intubated and mechanically ventilated, moderate or severe ARDS according to Berlin criteria (partial pressure of arterial blood oxygen to fraction of inspired oxygen (PaO2:FIO2) ratio of 200 or less.), onset of moderate or severe ARDS in less than 48h before randomization.
Open-label.
Multicenter, 41 intensive care units (ICUs) in Brazil.
The trial was stopped early following publication of a related study before reaching the planned sample size of 350 patients
dexamethasone (n=7) vs. standard of care (n=12)
randomized controlled trial low risk of bias
Dexamethasone
Dexamethasone 20 mg/iv/daily/from day 1 of randomization during 5 days, followed by 10 mg/iv/daily from day 6 to 10, plus standard of care.
Standard of care
Standard intensive care.
COVID-19 severe or critically
Age ≥ 18 years, positive reverse-transcriptase polymerase-chain-reaction (RT-PCR) assay for SARS-CoV-2 in a respiratory tract sample, intubated and mechanically ventilated, acute onset of moderate-to-severe ARDS, as defined by Berlin criteria, which includes (i) having pneumonia, (ii) bilateralpulmonary infiltrates on chest imaging (x-ray or CTscan), (iii) absence of left atrial hypertension or no clinicalsigns of left heart failure, and (iv) hypoxemia, as defined by a PaO2/FiO2 ratio of ≤ 200 mmHg on positive end-expiratory pressure (PEEP) of ≥ 5 cmH2O, regardless of FiO2.
Open-label
Multicenter, ICUs in teaching hospitals, Spain.
Study not published yet. Data and results come from Sterne J et al. meta-analysis, trial protocol and statistical plan. Planned sample size: 200 patients.
dexamethasone (n=75) vs. tocilizumab (n=74)
randomized controlled trial high risk of bias
Dexamethasone
Standard of care plus pulse dexamethasone 4 mg/kg/day in an infusion form for 3 days, followed by a maintenance dose of 8 mg/day for ten days.
Tocilizumab
Standard of care plus tocilizumab 4 mg/kg/dose in 100 cc normal saline over one hour repeated afer 24 h, then patient continue symptomatic treatment and oxygen therapy and/or assisted ventilation as needed.
All patients received standard of care.
COVID-19 severe or critically
Patients with signifcant deterioration in respiratory clinical status with respiratory rate>30 cycle/minute, Bilateral ChestmL) computed tomography (CT) infltration>30%, PaO2/FiO2 ratio<150 or saturation<90 on>6 L/min, Two positive laboratory tests of the following: (CRP>10 g/L, lymphocytes<600/mm3, D-dimer>500 ng/mL , ferritin>500 ng/mL). Patients who were not requiring supplemental oxygen were excluded from the study.
Open-label.
ICU of ESNA hospital, Egypt.
Dexamethasone 12mg (n=497) vs. dexamethasone 6mg (n=485)
randomized controlled trial low risk of bias
Dexamethasone 12mg
Standard of care plus intravenous bolus injection of dexamethasone 12 mg once daily for up to 10 days.
Dexamethasone 6mg
Standard of care plus intravenous bolus injection of dexamethasone 6 mg once daily for up to 10 days.
Betamethasone (12mg or 6mg) use was allowed at sites where dexamethasone was not available.
COVID-19 severe or critically
Aged 18 years or above AND confirmed SARS-CoV-2 (COVID-19) requiring hospitalisation AND use of one of the following: Invasive mechanical ventilation OR Non-invasive ventilation or continuous use of continuous positive airway pressure (CPAP) for hypoxia OR Oxygen supplementation with an oxygen flow of at least 10 L/min independent of delivery system.
Double-blind.
Multicenter: 26 hospitals in Europe (Denmark, Sweden, Switzerland) and India.
Hydrocortisone (n=76) vs. placebo (n=73)
randomized controlled trial low risk of bias
Low-dose Hydrocortisone
Continuous intravenous infusion of hydrocortisone at an initial dose of 200mg/d. Treatment was continued at 200mg/d until day 7 and then decreased to 100 mg/d for 4 days and 50 mg/d for 3 days, for a total of 14 days. If improvement by day 4, a short treatment regimen was used for a total of 8 days.
Placebo
Saline in a form guaranteeing double-blinding.
Patients received standard care for acute respiratory failure.
COVID-19 severe or critically
Patients aged at least 18 years admitted to 1 of the 9 participating French ICUs for acute respiratory failure with a biologically confirmed (reverse transcriptase–polymerase chain reaction) or suspected (suggestive chest computed tomography scan result in the absence of any other cause of pneumonia) COVID-19. The experimental treatment had to be administered within 24 hours of the onset of the first severity criterion (see below) or within 48 hours for patients referred from another hospital. One of 4 severity criteria had to be present: need for mechanical ventilation with a positive end-expiratory pressure (PEEP) of 5 cm H20 or more; a ratio of PaO2 to fraction of inspired oxygen (FIo2) less than 300 on high-flow oxygen therapy with an FIO2 value of at least 50%; for patients receiving oxygen through a reservoir mask, a PaO2:FIO2 ratio less than 300, estimated using prespecified charts; or a Pulmonary Severity Index greater than 130.
Double-blind.
Multicenter, 9 ICUs in France.
The trial was stopped early following the recommendation of the data and safety monitoring board after the publication of RECOVERY's results.
Hydrocortisone (n=16) vs. placebo (n=14)
randomized controlled trial low risk of bias
Hydrocortisone
IV hydrocortisone 200mg/day for 7 days or until hospital discharge whichever came first. (Continuous infusion over 24 hours or bolus injections every 6 hours (50 mg per bolus)).
Placebo
Matching placebo IV for 7 days or until hospital discharge. (Continuous infusion over 24 hours or bolus injections every 6 hours).
The injections had identical appearances. All other interventions were given at the discretion of the treating clinicians.
COVID-19 severe or critically
Aged 18 years or above AND Confirmed SARS-CoV-2 (COVID-19) requiring hospitalisation ANDUse of one of the following: Invasive mechanical ventilation OR Non-invasive ventilation or continuous use of continuous positive airway pressure (CPAP) for hypoxia OR Oxygen supplementation with an oxygen flow of at least 10 L/min independent of delivery system.
Double-blind.
Multicenter
The trial was terminated early when 30 out of 1,000 participants had been enrolled because of external evidence indicating benefit from corticosteroids in severe COVID-19.
Hydrocortisone (n=143) vs. standard of care (n=108)
randomized controlled trial high risk of bias
Hydrocortisone
Fixed 7-day course of intravenous hydrocortisone (50mg or 100mg every 6 hours).
Standard of care
No corticosteroids
COVID-19 severe or critically
1. Adult patient admitted to an ICU for acute severe CAP within 48 hours of hospital admission with a. symptoms or signs or both that are consistent with lower respiratory tract infection (for example, acute onset of dyspnea, cough, pleuritic chest pain) AND b. Radiological evidence of new onset infiltrate of infective origin (in patients with preexisting radiological changes, evidence of new infiltrate) 2. Up to 48 hours after ICU admission, receiving organ support with one or more of: a. Non-invasive or invasive ventilatory support; b. Receiving infusion of vasopressor or inotropes or both.
Open-label
121 sites in 8 countries (Australia, Canada, France, Ireland, Netherlands, New Zealand, UK, US).
Prematurely discontinuated due to external results
Hydrocortisone (n=152) vs. standard of care (n=108)
randomized controlled trial high risk of bias
Hydrocortisone
Shock-dependent course (50mg every 6 hours when shock was clinically evident).
Standard of care
No corticosteroids
COVID-19 severe or critically
1. Adult patient admitted to an ICU for acute severe CAP within 48 hours of hospital admission with a. symptoms or signs or both that are consistent with lower respiratory tract infection (for example, acute onset of dyspnea, cough, pleuritic chest pain) AND b. Radiological evidence of new onset infiltrate of infective origin (in patients with preexisting radiological changes, evidence of new infiltrate) 2. Up to 48 hours after ICU admission, receiving organ support with one or more of: a. Non-invasive or invasive ventilatory support; b. Receiving infusion of vasopressor or inotropes or both.
Open-label.
121 sites in 8 countries (Australia, Canada, France, Ireland, the Netherlands, New Zealand, UK, US).
Prematurely discontinuated due to external results
methylprednisolone (n=14) vs. control (n=15)
randomized controlled trial risk of bias NA
Methylprednisolone pulse
Methylprednisolone (1000 mg/day for three days, IV), and oral prednisolone 1 mg/kg with tapering of dose within ten days
Standard of care only
Kaletra (lopinavir/ritonavir) daily, Hydroxychloroquine 400 mg daily, Azithromycin 500 mg daily.
Standard of care in both groups: Kaletra (lopinavir/ritonavir) daily, Hydroxychloroquine 400 mg daily, Azithromycin 500 mg daily, oxygen therapy, nutritional support.
COVID-19 severe or critically
Double-blind
Phase 2
methylprednisolone (n=24) vs. standard of care (n=23)
randomized controlled trial some concerns about risk of bias
Methylprednisolone (high dose)
Methylprednisolone 40 mg IV every 12h for 5 days plus standard of care.
Standard of care
Standard of care only.
COVID-19 severe or critically
Adult patients with 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, and requiring ICU admission.
Open-label.
Medical ICU,peking union medical college hospital, China.
Data and results come from Sterne J et al. meta-analysis and study registry. Planned sample size: 80 patients.
methylprednisolone (n=34) vs. standard of care (n=34)
randomized controlled trial high risk of bias
Methylprednisolone pulse
Methylprednisolone pulse (intravenous injection, 250 mg/day for 3 days) plus standard care.
Standard care
Hydroxychloroquine sulfate, lopinavir, and naproxen. Patients did not receive methylprednisolone or other glucocorticoids.
All patients received standard care (Hydroxychloroquine sulfate, Lopinavir, and Naproxen) for COVID-19 according to the protocol for diagnosis and treatment of COVID-19 in Iran. In the standard care group, six patients received corticosteroids by the attending physician during treatment and excluded from the ITT population.
COVID-19 severe or critically
Aged 18 years or older, confirmed COVID-19 with blood oxygen saturation <90%, elevated C-reactive protein (CRP >10), and interleukin (IL)-6 (>6) at the early pulmonary phase of disease before connecting to the ventilator and intubation and agreed to give informed consent. The diagnosis of COVID-19 in subjects was performed based on the following criteria: 1. Identification of SARS-CoV-2 via reverse transcription-polymerase chain reaction (RT-PCR) in nasopharyngeal swab or sputum samples and 2. Abnormal computed tomography (CT) scan finding (bilateral, subpleural, peripheral ground-glass opacities) with oxygen saturation <90% at rest.
Single-blind.
2 centers: Imam Khomeini Hospital and Khorshid Hospital, Iran.
Improvement was defined as BORG score>3, improved dyspnea, stopped fever for 72 hours,SO2> 93%, tolerated oral regimen (PO), normal urinary output and reduced CRP levelwithout any treatment side effects.
Phase II.
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