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Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis

Mehra et al., The Lancet, May 22, 2020, doi: 10.1016/S0140-6736(20)31180-6
May 2020  
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HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
*, now known with p < 0.00000000001 from 422 studies, recognized in 42 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,100+ studies for 60+ treatments.
Incorrect at first read (implausible death, ventilation, and population numbers). This paper was retracted.
Mehra et al., 22 May 2020, peer-reviewed, 4 authors.
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RETRACTED: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis
Prof Mandeep R Mehra, Sapan S Desai, Prof Frank Ruschitzka, Amit N Patel
The Lancet, doi:10.1016/s0140-6736(20)31180-6
Background Hydroxychloroquine or chloroquine, often in combination with a second-generation macrolide, are being widely used for treatment of COVID-19, despite no conclusive evidence of their benefit. Although generally safe when used for approved indications such as autoimmune disease or malaria, the safety and benefit of these treatment regimens are poorly evaluated in COVID-19. Methods We did a multinational registry analysis of the use of hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19. The registry comprised data from 671 hospitals in six continents. We included patients hospitalised between Dec 20, 2019, and April 14, 2020, with a positive laboratory finding for SARS-CoV-2. Patients who received one of the treatments of interest within 48 h of diagnosis were included in one of four treatment groups (chloroquine alone, chloroquine with a macrolide, hydroxychloroquine alone, or hydroxychloroquine with a macrolide), and patients who received none of these treatments formed the control group. Patients for whom one of the treatments of interest was initiated more than 48 h after diagnosis or while they were on mechanical ventilation, as well as patients who received remdesivir, were excluded. The main outcomes of interest were in-hospital mortality and the occurrence of de-novo ventricular arrhythmias (non-sustained or sustained ventricular tachycardia or ventricular fibrillation). Findings 96 032 patients (mean age 53•8 years, 46•3% women) with COVID-19 were hospitalised during the study period and met the inclusion criteria. Of these, 14 888 patients were in the treatment groups (1868 received chloroquine, 3783 received chloroquine with a macrolide, 3016 received hydroxychloroquine, and 6221 received hydroxychloroquine with a macrolide) and 81 144 patients were in the control group. 10 698 (11•1%) patients died in hospital. After controlling for multiple confounding factors (age, sex, race or ethnicity, body-mass index, underlying cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition, and baseline disease severity), when compared with mortality in the control group (9•3%), hydroxychloroquine (18•0%; hazard ratio 1•335, 95% CI 1•223-1•457), hydroxychloroquine with a macrolide (23•8%; 1•447, 1•368-1•531), chloroquine (16•4%; 1•365, 1•218-1•531), and chloroquine with a macrolide (22•2%; 1•368, 1•273-1•469) were each independently associated with an increased risk of in-hospital mortality. Compared with the control group (0•3%), hydroxychloroquine (6•1%; 2•369, 1•935-2•900), hydroxy chloroquine with a macrolide (8•1%; 5•106, 4•106-5•983), chloroquine (4•3%; 3•561, 2•760-4•596), and chloroquine with a macrolide (6•5%; 4•011, 3•344-4•812) were independently associated with an increased risk of de-novo ventricular arrhythmia during hospitalisation. Interpretation We were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used..
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Late treatment
is less effective
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