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0 0.5 1 1.5 2+ Not reaching lowest sy.. 60% Improvement Relative Risk Not reaching lowes.. (b) 50% Time to first occurrence of.. 43% Time to release from qu.. 27% primary HCQ  Amaravadi et al.  EARLY TREATMENT  DB RCT Is early treatment with HCQ beneficial for COVID-19? Double-blind RCT 29 patients in the USA (April - July 2020) Improved recovery with HCQ (not stat. sig., p=0.13) c19hcq.org Amaravadi et al., medRxiv, February 2021 Favors HCQ Favors control

Hydroxychloroquine for SARS-CoV-2 positive patients quarantined at home: The first interim analysis of a remotely conducted randomized clinical trial

Amaravadi et al., medRxiv, doi:10.1101/2021.02.22.21252228
Feb 2021  
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HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
 
*, now known with p < 0.00000000001 from 421 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.
3,800+ studies for 60+ treatments. c19hcq.org
Tiny early-terminated 34 patient RCT for outpatient treatment showing faster recovery with treatment (not statistically significant). All patients recovered (3 control patients recovered after crossover to the treatment arm) - as per protocol mid-recovery results have priority. There was no mortality and only one hospitalization on day 0 before treatment. There were no severe adverse events.
risk of not reaching lowest symptom score at day 7 mid-recovery, 60.0% lower, RR 0.40, p = 0.13, treatment 3 of 15 (20.0%), control 6 of 12 (50.0%), NNT 3.3.
risk of not reaching lowest symptom score at day 5 mid-recovery, 50.0% lower, RR 0.50, p = 0.13, treatment 5 of 15 (33.3%), control 8 of 12 (66.7%), NNT 3.0.
relative time to first occurrence of lowest symptom score, 42.9% lower, relative time 0.57, p = 0.38, treatment median 4.0 IQR 13.0 n=15, control median 7.0 IQR 10.0 n=12.
relative time to release from quarantine, 27.3% lower, relative time 0.73, p = 0.46, treatment median 8.0 IQR 15.0 n=16, control median 11.0 IQR 14.0 n=13, primary outcome.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Amaravadi et al., 26 Feb 2021, Double Blind Randomized Controlled Trial, USA, preprint, 20 authors, study period 15 April, 2020 - 14 July, 2020, dosage 400mg bid days 1-14.
This PaperHCQAll
Hydroxychloroquine for SARS-CoV-2 positive patients quarantined at home: The first interim analysis of a remotely conducted randomized clinical trial
MD Ravi K Amaravadi, Lydia Giles, Mary Carberry, MD PhD Matthew C Hyman, MD Ian Frank, MD Sunita D Nasta, Jennifer Walsh, E Paul Wileyto, PhD Phyllis Gimotty, MD PhD Michael Milone, BA Edith M Teng, MBS Niraj J Vyas, MD Steve Balian, BA Jonathan A Kolansky, BS Nabil M Abdulhay, BS BSN Shaun K Mcgovern, BA Sarah Gamblin, BS Olivia Doran, BA Paul L Callahan, MD MPhil Benjamin S Abella
doi:10.1101/2021.02.22.21252228
Background Older patients are at risk of increased morbidity and mortality from COVID-19 disease due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There are few effective treatments for outpatients with COVID-19. Objective To evaluate the efficacy of hydroxychloroquine to reduce time in quarantine for symptomatic ≥40 years-old COVID-19 patients. Design A randomized, double-blind, placebo-controlled clinical trial. Setting Outpatients with polymerase chain reaction confirmed COVID-19 at a University of Pennsylvania affiliated testing center between April 15, 2020 and, July 14, 2020. Participants Out of 5511 SARS-CoV-2 positive patients, 1072 met initial eligibility criteria for telephonebased recruitment, but only 34 subjects were able to be randomized. Interventions Hydroxychloroquine 400 mg per twice daily (n=17) or matching placebo (n=17), taken orally for up to 14 days. Measurements The primary outcome was the time to release from quarantine. Secondary outcomes included the participant-reported secondary infection of co-inhabitants, hospitalization, treatment-related adverse events, time to symptom improvement, and incidence of cardiac arrhythmia. Results .
References
Alexander, Debono, Mammen, Iorio, Aryal et al., COVID-19 coronavirus research has overall low methodological quality thus far: case in point for chloroquine/hydroxychloroquine, J Clin Epidemiol, doi:10.1016/j.jclinepi.2020.04.016
Burton, Fort, Seoane, Hospitalization and Mortality among Black Patients and White Patients with Covid-19, N Engl J Med, doi:10.1056/NEJMsa2011686
Group, Horby, Mafham, Linsell, Bell et al., Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19, N Engl J Med, doi:10.1056/NEJMoa2022926
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Mehra, Desai, Ruschitzka, Patel, RETRACTED: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis, Lancet, doi:10.1016/S0140-6736(20)31180-6
Northwell, Barnaby, Becker, Chelico, Cohen et al., Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area, JAMA, doi:10.1001/jama.2020.6775
Nurchis, Pascucci, Sapienza, Villani, 'ambrosio et al., Impact of the Burden of COVID-19 in Italy: Results of Disability-Adjusted Life Years (DALYs) and Productivity Loss, Int J Environ Res Public Health, doi:10.3390/ijerph17124233
Richardson, Hirsch, Narasimhan, Crawford, Mcginn et al., the
Skipper, Pastick, Engen, Bangdiwala, Abassi et al., Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19: A Randomized Trial, Ann Intern Med, doi:10.7326/M20-4207
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