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 registered, https://www.clinicaltrials.gov/ct2/show/study/NCT04420247 .
【초록키워드】 COVID-19, Treatment, coronavirus disease, Brazil, SARS-CoV-2, Coronavirus disease 2019, Efficacy, coronavirus, Chloroquine, Trial, Open-label, Hydroxychloroquine, randomization, severe COVID-19, hospital, drugs, risk, severe acute respiratory syndrome Coronavirus, clinical status, Clinical outcome, outcomes, Randomized, Patient, Follow-up, incidence, respiratory, positive RT-PCR, Ordinal Scale, Combination, Invasive mechanical ventilation, cardiovascular complications, Odds ratio, risk ratio, chloroquine/hydroxychloroquine, once daily, cardiovascular complication, acute respiratory syndrome, Sample size, Primary outcome, intervention group, Trial registration, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, standard care, increased risk, standard treatment, mITT, worsening, all-cause mortality, 105 patients, 9-point ordinal scale, acute renal dysfunction, arrythmia, Arrythmias, doubt, Registered, renal dysfunction, severe renal dysfunction, secondary outcome, KDIGO, Administered, Effect, Effects, FIVE, enrolled, analyzed, evaluate, the disease, form, added, 105 patient, intention to treat, patients hospitalized, were assessed, 【제목키워드】 Randomized controlled trial, Efficacy, severe COVID-19 patient,