Article |
Population of interest |
Intervention |
Outcomes of interest |
Results |
Observations |
Single-arm interventional studies |
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J. M. Molina et al. (France, March 30th, 2020) |
Confirmed
hospitalized COVID-19 consecutive cases (n=11) |
HCQ 200 mg Q8h D1-D10)
+ AZI (500 mg D1 and 250 mg D2-D5). |
Viral negative conversion and
clinical outcomes |
Nasopharyngeal PCR was positive in 8/10 (80%)
patients at D6. 1/11 (0.9%) patient died, 2/11 (18.2%) patients were
transferred to the ICU. 1/11 (0.9%) had prolongation of QTc |
10/11
(91%) of patients required supplemental oxygen at the time of treatment
initiation. The time between onset of symptoms and treatment initiation
was not specified. |
P. Gautret et al. (France, April 11th, 2020) |
Confirmed
hospitalized COVID-19 cases with mild COVID-19 to severe COVID-19
pneumonia (n=80) |
HCQ (200 mg Q8h D1-D10) + AZI (500 mg D1 and 250 mg
D2-D5). |
ICU transfer and oxygen requirement after D3, length of
hospitalization, virus contagiousness (PCR cycle threshold value, and
viral culture) |
3/80 (0.4%) patients required supplemental oxygen,
12/80 (15%) patients required ICU transfer, 1/80 (1.3%) patient died
upon publication date. Mean length of hospitalization in the ward was
4.6 days. No patient was presumably contagious by D12. |
69/75 (92%)
patients had low NEWS at baseline. |
Retrospective studies |
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J. Magagnoli et al. (US, April 21st 2020) |
Confirmed
hospitalized cases (n=368) |
HCQ (n= 97), HCQ + azithromycin (n=113),
SOC (n=158) |
In-hospital mortality and need for mechanical ventilation |
HCQ was associated with greater in-hospital mortality compared to SOC.
Risk of mechanical ventilation was similar between groups. |
Patient in
the treatment arms had more severe disease at baseline. The study
included only men, most were African-Americans (64%), and older (median
age 65) |
M. Million et al. (France, May 5th 2020) |
Confirmed cases with
asymptomatic infection to severe COVID-19 pneumonia (n=1062) |
HCQ (200
mg Q8h D1-D10) + AZI (500 mg/d D1, 250 mg D2-D5) |
In-hospital
mortality, need for ICU, length of hospitalization > 10
days, viral shedding > 10 days |
46/1061 (4.3%) patients
had a poor outcome (need for mechanical ventilation and/or death),
8/1061 (0.8%) patients died of respiratory failure. 91.7% patients had
viral negative conversion at D10. |
95% os patients had relatively mild
disease (low NEWS) |
M. R. Mehra et al. (Multinational, May 6th 2020) |
Confirmed
hospitalized cases (n=96031) |
CQ vs CQ + macrolide vs HCQ vs HCQ +
macrolide vs none |
In-hospital mortality and occurrence of
de-novo ventricular arrhythmias |
All treatment groups were
associated with increased in-hospital mortality and de-novo
ventricular arrhythmias. |
Study was retracted. Data and statistical
analysis were not shared with an independent group of researchers for
evaluation. |
E. S. Rosenberg et al. (US, May 11th 2020) |
Confirmed
hospitalized cases (n=1438) |
HCQ (n=271) vs AZI (n=211) vs HCQ + AZI
(n=735) vs SOC (n=221) |
In-hospital mortality |
In-hospital mortality
was similar between groups. Treatment arms were associated with
increased risk of cardiac arrest compared to SOC. |
Patients receiving
HCQ with or without AZI were more likely to be male, have pre-existing
conditions, and more severe disease at presentation. Readmissions were
not captured. |
B. Yu et al. (China, May 15th 2020) |
Confirmed cases with severe
COVID-19 pneumonia requiring mechanical ventilation (n=550) |
HCQ (n=48,
200 mg Q12h D1-D7 or D10) vs SOC (n=512) |
In-hospital mortality,
inflammatory cytokine levels |
HCQ was associated with decreased
mortality and mortality was lower among patients who were started on HCQ
within 5 days of admission compared to the ones who were started later.
HCQ was associated with decrease in IL-6 levels |
It was not specified
how the HCQ group was selected |
M. Mahévas et al. (France, May 24th 2020) |
Confirmed
hospitalized cases of COVID-19 pneumonia requiring supplemental oxygen,
but not mechanical ventilation (n=181) |
HCQ (n=84, 600 mg/d) vs SOC
(n=89) |
Survival without transfer to the ICU at D21, overall survival,
survival without ARDS, weaning of supplemental oxygen, hospital
discharge to home or rehabilitation at D21 |
HCQ was not associated with
differences in survival, ICU transfer, weaning of supplemental oxygen.
8/92 (8.7%) patients in the HCQ group experienced EKG changes that
required HCQ discontinuation. |
The decision on whether or not to use
HCQ were based on centre’s protocols and not on individual’s clinical
presentation |
J. Geleris et al. (US, June 18th 2020) |
Confirmed hospitalized
consecutive cases (n=1376) |
HCQ (n=811, 600 mg Q12h D1, 400 mg/d for a
median of 5 days) with or without AZI vs SOC |
In-hospital mortality and
need for mechanical ventilation |
HCQ was not associated with use of
mechanical ventilation or death |
Patients in the HCQ group were more
severely ill at baseline |
S. Arshad et al. (US, July 2nd 2020) |
Confirmed hospitalized
cases (n=2541) |
HCQ (n=1202, 400 mg Q12h D1, 200 mg Q12h D2-D5), AZI
(n=147, 500 mg D1, 250 mg D2-D5), HCQ+ AZI (n=783) vs SOC (n=409) |
In-hospital mortality |
HCQ alone and HCQ+ AZI were associated with
decreased hazard of in-hospital death |
Patients on HCQ and AZI were
more likely to have received corticosteroids or
tocilizumab. |
Prospective, interventional and controlled studies: |
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P. Gautret et al. (France, March 20th, 2020) |
Confirmed cases with
asymptomatic infection to severe COVID-19 pneumonia (n=36) |
HCQ (n=20,
200 mg Q8h D1-D10) vs SOC (n=16) |
Viral negative conversion at D6,
virologic clearance at D14, symptoms, length of hospitalization, and
mortality. |
Nasopharyngeal PCR was more likely to be negative in the
HCQ group at D6. |
6/26 (23.1%) patients in the HCQ group were not
counted in the analysis due to loss of follow up or early cessation of
therapy. 3/6 (50%) of these patients were transferred to the
ICU. |
Z. Chen et al. (China, April 1st, 2020) |
Confirmed hospitalized
cases with mild COVID-19 pneumonia (n=62) |
HCQ (n=31, 400 mg/d D1-D5)
vs SOC (n=31) |
Clinical recovery in 5 days; chest radiographic follow
up in 5 days. |
Time to defervescence and cough was shorter in the HCQ
group. Pneumonia radiographic improvement was more common in the HCQ
group. |
Young patients (mean 44.7), mostly women (53.2%). Fever and
cough was more prevalent in the HCQ arm at baseline. |
M. G. Silva Borba et al. (Brazil, April 24th 2020) |
Suspected
hospitalized cases with severe COVID-19 pneumonia (n=81) |
CQ (n=41, 600
mg Q12h D1-D10) vs CQ (n=40, 450 mg Q12h D1, 450 mg/day D2-D5) |
In-hospital mortality, adverse events, clinical status, viral negative
conversion on D4 |
Mortality was higher in the high-dose CQ group at
D13. QTc prolongation was more common in the high-dose CQ group. |
Patients in the high-dose CQ group were older and had more heart
disease. All patients received AZI and most have received oseltamivir.
14/51 (27.5%) patients had alcohol use disorder. |
W. Tang et al. (China, May 4th , 2020) |
Confirmed hospitalized cases with mild to moderate COVID-19 (n=150) |
HCQ (n=75, 1200 mg/d D1-D3, then HCQ 800 mg/d until D14 or D21) vs SOC
(n=75) |
Viral negative conversion at D28, clinical and radiographic
improvement |
Probability of viral negative conversion and alleviation
of symptoms was similar between HCQ and SOC at D28. 30/70 (43%)
patients reported adverse events, 2/70 (2.9%) patients reported severe
adverse events due to disease progression and upper respiratory tract
infection. |
Results on clinical, laboratory, and radiographic
improvement were not reported due to under-powered sample size. Median
of 16 days between symptoms onset and HCQ initiation. |
D. R. Boulware et al. (US and Canada, June 3rd 2020) |
Asymptomatic participants who had moderate or high risk exposure to
confirmed cases of COVID-19 (n=821) |
HCQ (n=414, 800 mg once, then 600
mg in 6-8h, then 600 mg D2-D5) vs placebo (n=407) |
Incidence of either
laboratory confirmed or illness compatible with COVID-19 |
HCQ and
placebo groups had similar incidence of laboratory confirmed or
clinically suspected cases of COVID-19 |
Participants were overall young
(median age 40), women (51.6%), healthy (75% did not have pre-existing
hypertension, asthma, diabetes) |
P. W. Horby et al. (UK, June 4th 2020) |
Suspected or confirmed
hospitalized cases (n=4761) |
HCQ (n=1561, 800 mg once then in 6h, 400
mg at 12h, then 400 mg Q12h D2-D10) vs SOC (n=3155) |
Mortality in D28,
length of hospitalization, need for mechanical ventilation, need for
hemodialysis, incidence of major cardiac arrhythmia |
Patients in the
HCQ arm were less likely to be discharged alive from the hospital and
were more likely to reach a composite score of mechanical ventilation
and death. There was one case of torsades de pointes in the HCQ arm. |
Preliminary results did not include case-specific mortality or other
clinical and laboratory data. |
A. B Cavalcanti et al. (Brazil, July 23rd 2020) |
Suspected or
confirmed cases with mild-to-moderate COVID-19 requiring no oxygen or
maximum of 4L O2 supplementation (n=665) |
HCQ (n=221, 400 mg Q12 D1-D7)
vs HCQ + AZI (n=217, HCQ 400 mg Q12h D1-D7 and AZI 500 mg/d for D1-D5)
vs SOC (n=227) |
Clinical outcomes assessed by a 7-levels ordinal scale
and adverse events |
HCQ or HCQ+ AZI were not associated with a
difference in the 7-points ordinal scale, need of mechanical
ventilation, deaths, and thromboembolic complications compared to usual
of care group. QTc prolongation and elevation of liver enzymes were more
common in the treatment arms. |
Median time from symptom onset to
randomization was 7 days |
HCQ: hydroxychloroquine, CQ: chloroquine,
AZI: azithromycin, SOC: standard of care, D
(1-28): Day (1-28), Q8h/Q12h: every 8h/ every 12h,
ICU: intensive care unit |
HCQ: hydroxychloroquine,
CQ: chloroquine, AZI: azithromycin, SOC:
standard of care, D (1-28): Day (1-28), Q8h/Q12h:
every 8h/ every 12h, ICU: intensive care unit |
HCQ:
hydroxychloroquine, CQ: chloroquine, AZI:
azithromycin, SOC: standard of care, D (1-28): Day
(1-28), Q8h/Q12h: every 8h/ every 12h, ICU: intensive
care unit |
HCQ: hydroxychloroquine, CQ: chloroquine,
AZI: azithromycin, SOC: standard of care, D
(1-28): Day (1-28), Q8h/Q12h: every 8h/ every 12h,
ICU: intensive care unit |
HCQ: hydroxychloroquine,
CQ: chloroquine, AZI: azithromycin, SOC:
standard of care, D (1-28): Day (1-28), Q8h/Q12h:
every 8h/ every 12h, ICU: intensive care unit |
HCQ:
hydroxychloroquine, CQ: chloroquine, AZI:
azithromycin, SOC: standard of care, D (1-28): Day
(1-28), Q8h/Q12h: every 8h/ every 12h, ICU: intensive
care unit |
Confirmed cases: confirmed by SARS-CoV-2 RNA by PCR from
nasopharyngeal sample or other confirmatory laboratory assay specific
for the virus. |
Confirmed cases: confirmed by SARS-CoV-2 RNA
by PCR from nasopharyngeal sample or other confirmatory laboratory assay
specific for the virus. |
Confirmed cases: confirmed by
SARS-CoV-2 RNA by PCR from nasopharyngeal sample or other confirmatory
laboratory assay specific for the virus. |
Confirmed cases:
confirmed by SARS-CoV-2 RNA by PCR from nasopharyngeal sample or other
confirmatory laboratory assay specific for the virus. |
Confirmed cases: confirmed by SARS-CoV-2 RNA by PCR from
nasopharyngeal sample or other confirmatory laboratory assay specific
for the virus. |
Confirmed cases: confirmed by SARS-CoV-2 RNA
by PCR from nasopharyngeal sample or other confirmatory laboratory assay
specific for the virus. |
NEWS (National Early Warning Score): scoring system designed to
be applied to hospitalized patients to allow for early detection of
clinical deterioration. NEWS 1-4 (low score), NEWS 5-6 (medium score),
NEWS >=7 (high score) |
NEWS (National Early
Warning Score): scoring system designed to be applied to hospitalized
patients to allow for early detection of clinical deterioration. NEWS
1-4 (low score), NEWS 5-6 (medium score), NEWS >=7 (high
score) |
NEWS (National Early Warning Score): scoring system
designed to be applied to hospitalized patients to allow for early
detection of clinical deterioration. NEWS 1-4 (low score), NEWS 5-6
(medium score), NEWS >=7 (high score) |
NEWS
(National Early Warning Score): scoring system designed to be applied to
hospitalized patients to allow for early detection of clinical
deterioration. NEWS 1-4 (low score), NEWS 5-6 (medium score), NEWS
>=7 (high score) |
NEWS (National Early Warning
Score): scoring system designed to be applied to hospitalized patients
to allow for early detection of clinical deterioration. NEWS 1-4 (low
score), NEWS 5-6 (medium score), NEWS >=7 (high score) |
NEWS (National Early Warning Score): scoring system designed to
be applied to hospitalized patients to allow for early detection of
clinical deterioration. NEWS 1-4 (low score), NEWS 5-6 (medium score),
NEWS >=7 (high score) |