An open-label randomized controlled trial evaluating the efficacy of chloroquine/hydroxychloroquine in severe COVID-19 patients
Early terminated very late stage (99% on oxygen, 81% in ICU, 18% on mechanical ventilation at baseline) RCT with 24 CQ patients, 29 HCQ, and 52 control patients, showing worse clinical outcomes with treatment. NCT04420247 (history)
risk of death, 57.0% higher, RR 1.57, p = 0.20, treatment 16 of 53 (30.2%), control 10 of 52 (19.2%).
risk of mechanical ventilation, 115.0% higher, RR 2.15, p = 0.03, treatment 53, control 52.
9-point scale clinical status, 147.0% higher, OR 2.47, p = 0.02, treatment 53, control 52, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Réa-Neto et al., 27 Apr 2021, Randomized Controlled Trial, Brazil, peer-reviewed, 6 authors, average treatment delay 8.0 days, trial NCT04420247 (history)
An open‑label randomized
controlled trial evaluating
the efficacy of chloroquine/
hydroxychloroquine in severe
Álvaro Réa‑Neto1*, Rafaella Stradiotto Bernardelli2, Bruna Martins Dzivielevski Câmara2,
Fernanda Baeumle Reese2, Marcos Vinicius Oliveira Queiroga2 & Mirella Cristine Oliveira2
Despite several studies designed to evaluate the efficacy of chloroquine and hydroxychloroquine in
the treatment of coronavirus disease 2019 (COVID-19), there is still doubt about the effects of these
drugs, especially in patients with severe forms of the disease. This randomized, open-label, controlled,
phase III trial assessed the efficacy of chloroquine or hydroxychloroquine for five days in combination
with standard care compared to standard care alone in patients hospitalized with severe COVID-19.
Chloroquine 450 mg BID on day 1 and 450 mg once daily from days 2 to 5 or hydroxychloroquine
400 mg BID on day 1 and 400 mg once daily from days 2 to 5 were administered in the intervention
group. Patients were enrolled from April 16 to August 06, 2020, in 6 hospitals in southern Brazil.
The primary outcome was the clinical status measured on day 14 after randomization with a 9-point
ordinal scale. The main secondary outcomes were all-cause mortality; invasive mechanical ventilation
use; the incidence of acute renal dysfunction in 28 days; and the clinical status of patients on days
5, 7, 10 and 28. All patients with a positive RT-PCR result for severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) were analyzed (modified intention to treat (mITT) population). Arrythmias
and cardiovascular complications were assessed as safety outcomes. A total of 105 patients were
enrolled and followed for 28 days. The trial was stopped before reaching the planned sample size due
to harmful effects. Patients in the intervention group had a worse clinical outcome on the 14th day
(odds ratio (OR) 2.45 [1.17 to 4.93], p = 0.016) and on the 28th day (OR 2.47 [1.15 to 5.30], p = 0.020).
Moreover, the intervention group had higher incidences of invasive mechanical ventilation use (risk
ratio (RR) 2.15 [1.05 to 4.40], p = 0.030) and severe renal dysfunction (KDIGO stage 3) (RR 2.24 [1.01 to
4.99], p = 0.042) until the 28th day of follow-up. No significant arrythmia was noted. In patients with
severe COVID-19, the use of chloroquine/hydroxychloroquine added to standard treatment resulted in
a significant worsening of clinical status, an increased risk of renal dysfunction and an increased need
for invasive mechanical ventilation.
Trial Registration: ClinicalTrials.gov, NCT04420247. Registered 09 June 2020—Retrospectively
The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus
disease 2019 (COVID-19), has already infected tens of millions of people around the world and killed more than
a million people (approximately 3%)1. Patients with risk factors or severe forms of COVID-19 have more than a
30% chance of dying. Many antiviral or anti-inflammatory drugs have been studied to find a way to control the
poor outcomes of COVID-192. Some drugs have demonstrated in vitro activity against SARS-CoV-2 and potential
clinical benefits in small and/or observational studies3. In this scenario, experiments with chloroquine (Clq) and
its derivative hydroxychloroquine (HClq) revealed that these drugs..
is less effective
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