Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial
Furtado et al.
, Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients..
, The Lancet, doi:10.1016/S0140-6736(20)31862-6
Small RCT comparing the addition of AZ for very late stage patients on ventilation or oxygen. No significant difference was found, OR 1.36, p
=0.11. One notable result is that even within this extremely late stage population, results suggest increased efficacy with the addition of AZ for patients with earlier use of AZ/HCQ, OR 0.71, p
Patients received 8g of HCQ over 10 days, approaching the high levels used in the RECOVERY trial (9.2g over 10 days), showing significantly more adverse events than typical trials.
Since all patients were on HCQ, this study does not provide information on the efficacy of HCQ.
Furtado et al., 4 Sep 2020, peer-reviewed, 33 authors.
Azithromycin in addition to standard of care versus standard
of care alone in the treatment of patients admitted to the
hospital with severe COVID-19 in Brazil (COALITION II):
a randomised clinical trial
Remo H M Furtado*, Otavio Berwanger*, Henrique A Fonseca, Thiago D Corrêa, Leonardo R Ferraz, Maura G Lapa, Fernando G Zampieri,
Viviane C Veiga, Luciano C P Azevedo, Regis G Rosa, Renato D Lopes, Alvaro Avezum, Airton L O Manoel, Felipe M T Piza, Priscilla A Martins,
Thiago C Lisboa, Adriano J Pereira, Guilherme B Olivato, Vicente C S Dantas, Eveline P Milan, Otavio C E Gebara, Roberto B Amazonas,
Monalisa B Oliveira, Ronaldo V P Soares, Diogo D F Moia, Luciana P A Piano, Kleber Castilho, Roberta G R A P Momesso, Guilherme P P Schettino,
Luiz Vicente Rizzo, Ary Serpa Neto, Flávia R Machado, Alexandre B Cavalcanti, for the COALITION COVID-19 Brazil II Investigators†
Background The efficacy and safety of azithromycin in the treatment of COVID-19 remain uncertain. We assessed
whether adding azithromycin to standard of care, which included hydroxychloroquine, would improve clinical
outcomes of patients admitted to the hospital with severe COVID-19.
Methods We did an open-label, randomised clinical trial at 57 centres in Brazil. We enrolled 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. Patients were randomly assigned (1:1) to azithromycin (500 mg via oral,
nasogastric, or intravenous administration once daily for 10 days) plus standard of care or to standard of care without
macrolides. All patients received hydroxychloroquine (400 mg twice daily for 10 days) because that was part of standard
of care treatment in Brazil for patients with severe COVID-19. The primary outcome, assessed by an independent
adjudication committee masked to treatment allocation, was clinical status at day 15 after randomisation, assessed by a
six-point ordinal scale, with levels ranging from 1 to 6 and higher scores indicating a worse condition (with odds ratio
[OR] greater than 1·00 favouring the control group). The primary outcome was assessed in all patients in the intentionto-treat (ITT) population who had severe acute respiratory syndrome coronavirus 2 infection confirmed by molecular or
serological testing before randomisation (ie, modified ITT [mITT] population). Safety was assessed in all patients
according to which treatment they received, regardless of original group assignment. This trial was registered at
Findings 447 patients were enrolled from March 28 to May 19, 2020. COVID-19 was confirmed in 397 patients who
constituted the mITT population, of whom 214 were assigned to the azithromycin group and 183 to the control group.
In the mITT population, the primary endpoint was not significantly different between the azithromycin and control
groups (OR 1·36 [95% CI 0·94–1·97], p=0·11). Rates of adverse events, including clinically relevant ventricular
arrhythmias, resuscitated cardiac arrest, acute kidney failure, and corrected QT interval prolongation, were not
significantly different between groups.
Interpretation In patients with severe COVID-19, adding azithromycin to standard of care treatment (which included
hydroxychloroquine) did not improve..
is less effective
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