meta|Evidence - COVID-19
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azithromycin (n=214) vs. standard of care (n=183)
randomized controlled trial some concerns about risk of bias
azithromycin plus SoC
azithromycin (500 mg via oral, nasogastric, or intravenous administration once daily for 10 days) plus standard of care including HCQ 400 mg x2 for 10 days
standard of care without macrolide
Soc include HCQ 400 mg x2 for 10 days for all patients
All patients received hydroxychloroquine (400 mg twice daily for 10 days)
COVID-19 severe or critically
patients admitted to hospital with suspected or confirmed COVID-19 and at least one additional severity criteria as follows: use of oxygen supplementation of more than 4 L/min flow; use of high-flow nasal cannula; use of non-invasive mechanical ventilation; or use of invasive mechanical ventilation
open-label
57 centres in Brazil
Several sites enrolling patients in this trial were also participating in the COALITION I trial, another randomised study from our group that tested hydroxychloroquine, with or without azithromycin, in patients with mild to moderate COVID-19.14 Investigators were not allowed totransfer patients between trials, and co-enrolment was also not possible because the trials’ inclusion criteria were mutually exclusive.
hydroxychloroquine (n=106) vs. placebo (n=108)
randomized controlled trial some concerns about risk of bias
hydroxychloroquine
200x2 for 10 days
placebo
COVID-19 severe or critically
double-blind
3 centres, Mexico
pr-specified sample size : 300 vs 300. In mid-July, 2020, the rhythm of recruitment was reduced drastically, due to severalreasons including patient refusal, that of their relatives, or that of their treating physicians,coinciding with the worldwide suspension of several large trials testing HCQ in which no benefitsof the drug were found
hydroxychloroquine (n=61) vs. standard of care (n=81)
randomized controlled trial risk of bias NA
hydroxychloroquine
Loading dose of 800mg hydroxychloroquine administered enterally every 6 hours until 2 doses have been administered. Subsequently, 400mg hydroxychloroquine will be administered enterally every 12 hours for 12 doses or ICU discharge
standar of care
COVID-19 severe or critically
open label
90 centers, international
found in Axfors et al. meta-analysis
ivermectin (n=53) vs. chloroquine (n=115)
randomized controlled trial some concerns about risk of bias
Ivermectin
14 mg once at day 0 1 placebo tablet at day 0, and once daily from day 1 to day 2, 1 placebo tablet daily from day 3 to 4, total dose 42 mg
Hydroxychloroquine or Chloroquine
HCQ : 400 mg twice on day 0, and once daily from day 1 to day 4, total dose 2.4 gCQ : 450 mg, twice on day 0, and once daily from day 1 to day 4, total dose 2.7 g
3 arms: chloroquine, hydroxychloroquine, ivermectin.
COVID-19 severe or critically
Double-blind.
Single center, Brasil.
Phase II.
ivermectin (n=30) vs. standard of care (n=30)
randomized controlled trial high risk of bias
ivermectin soc
Ivermectin (Enteral solution at 200 microgr/kg/day (9mg between 36-50 kg, 12mg between 51-65 kg, 15mg between 66-79 kg and 200 microgram/kg in > 80 kg) for 5 days
Soc
Favipiravir (2x1600mg loading dose followed by 2x600mg maintenance dose, po, total 5 days); Hydroxychloroquine (2x400mg loading dose followed by 2x200mg, po, 5 days);Azithromycin (500mg first day loading dose, followed by 250mg/day, po, total 5 days)
COVID-19 severe or critically
single blind
4 centres, Turkey
described as crossover assignment and several inconsistencies in the description of endpoints in clinicalTrials.gov
results up-dated with pre-print
lopinavir/ritonavir (n=268) vs. standard of care (n=377)
randomized controlled trial some concerns about risk of bias
Lopinavir/ritonavir
400 mg of lopinavir and 100 mg of ritonavir every 12h for 5 days minimum, up to a maximum of 14 days or until ICU discharge whichever occurred first. Patients with a gastric tube who were unable to swallow tablets, lopinavir-ritonavir (at the same dose) was administered as a 5-ml suspension every 12h or alternatively as two dissolved tablets or four crushed tablets (double dose).
Standard of care
No antiviral treatment.
COVID-19 severe or critically
≥18 years old, admitted with suspected or confrmed COVID-19, and were receiving respiratory or cardiovascular organ failure support in an intensive care unit (ICU). Organ support included the provision of invasive mechanical ventilation, noninvasive mechanical ventilation, high-fow nasal cannulae with a fow rate of at least 30 L per minute and a fractionalinspired oxygen concentration of 0.4 or higher, or the infusion of vasopressor or inotropes for shock.
Open-label.
99 sites across 8 countries.
In the register PE was: all-cause mortality (day 90); days alive and not receiving organ support in ICU (day 21).
Enrollment into the lopinavir-ritonavir arm was halted on November 19, 2020, after reaching the prespecifed futility threshold.
lopinavir/ritonavir (n=99) vs. standard of care (n=100)
randomized controlled trial some concerns about risk of bias
Lopinavir–ritonavir
Lopinavir–ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care.
Standard care
Standard care alone.
Both groups received standard care: supplemental oxygen,noninvasive and invasive ventilation, antibiotic agents, vasopressor support, renal-replacement therapy, and extracorporeal membrane oxygenation (ECMO).
COVID-19 severe or critically
Male and nonpregnant female patients 18 years of age or older were eligible if they had a diagnostic specimen that was positive on RT-PCR, had pneumonia confirmed by chest imaging, and had an oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2)(Pao2:Fio2) at or below 300 mg Hg.
Open-label.
Single center, Jin Yin-Tan Hospital, Wuhan, Hubei Province, China.
The seven-category ordinal scale consisted of the following categories: 1, not hospitalized with resumption of normal activities; 2, not hospitalized,but unable to resume normal activities; 3, hospitalized, not requiring supplemental oxygen; 4,hospitalized, requiring supplemental oxygen; 5,hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; 6, hospitalized, requiring ECMO, invasive mechanical ventilation, or both; and 7, death.
Wuhan Infectious Diseases Hospital
Lopinavir/ritonavir plus hydroxychloroquine (n=29) vs. standard of care (n=377)
randomized controlled trial some concerns about risk of bias
Lopinavir/ritonavir plus hydroxychloroquine.
400 mg of lopinavir and 100 mg of ritonavir every 12h for 5 days minimum, up to a maximum of 14 days or until ICU discharge whichever occurred first. Hydroxychloroquine was administered as two loading doses of 800 mg, 6-h apart, followed 6 h later by 400 mg 12 hourly for 12 doses.
Standard of care
No antiviral treatment.
COVID-19 severe or critically
≥18 years old, admitted with suspected or confrmed COVID-19, and were receiving respiratory or cardiovascular organ failure support in an intensive care unit (ICU). Organ support included the provision of invasive mechanical ventilation, noninvasive mechanical ventilation, high-fow nasal cannulae with a fow rate of at least 30 L per minute and a fractionalinspired oxygen concentration of 0.4 or higher, or the infusion of vasopressor or inotropes for shock.
Open-label.
99 sites across 8 countries.
In the register PE was: all-cause mortality (day 90); days alive and not receiving organ support in ICU (day 21).
remdesivir (n=158) vs. placebo (n=79)
randomized controlled trial low risk of bias
Remdesivir
Intravenous remdesivir 200 mg on day 1 followed by 100 mg on days 2–10 in single daily infusions.
Placebo
Placebo matched remdesivir, loading dose on day 1 is given, followed by 100 mg iv once-daily maintenance doses for 9 days.
2:1 ratio. Concomitant use of lopinavir–ritonavir, interferons, and corticosteroids permitted.
COVID-19 severe or critically
Hospitalized patients with laboratory-confirmed SARS-CoV-2 infection, within 12 days of symptoms onset , oxygen saturation of 94% or less on ambient air or a ratio SaO2/FiO2 of 300 mm Hg or less, and radiologically confirmed pneumonia.
Double-blind.
10 hospitals in Hubei, China.
The six-point scale was as follows: death=6; hospital admission for extracorporeal membrane oxygenation or mechanical ventilation=5; hospital admission for noninvasive ventilation or high-flow oxygen therapy=4; hospital admission for oxygen therapy (but not requiring high-flow or non-invasive ventilation)=3; hospital admission but not requiring oxygen therapy=2; and discharged or having reached discharge criteria (defined as clinical recovery—ie, normalisation of pyrexia, respiratory rate <24 breaths per minute, saturation of peripheral oxygen >94% on room air, and relief of cough, all maintained for at least 72 h)=1.
Study prematurely discontinued because of the control of the outbreak in Wuhan after March 12.One patient in the placebo group who withdrew after randomisation was not included in the ITT population.
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