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All Studies   Meta Analysis    Recent:   
0 0.5 1 1.5 2+ Hospitalization 30% Improvement Relative Risk Recovery 2% Recovery (b) -10% Time to viral- 29% no CI Time to viral- (b) 14% no CI Viral clearance 38% Viral clearance (b) 20% HCQ  Johnston et al.  LATE TREATMENT  RCT Is late treatment with HCQ beneficial for COVID-19? RCT 231 patients in the USA (April - July 2020) Trial compares with vitamin C and folic acid Improved viral clearance with HCQ (p=0.047) c19hcq.org Johnston et al., EClinicalMedicine, Dec 2020 Favors HCQ Favors vitamin C an..

Hydroxychloroquine with or Without Azithromycin for Treatment of Early SARS-CoV-2 Infection Among High-Risk Outpatient Adults: A Randomized Clinical Trial

Johnston et al., EClinicalMedicine, doi:10.1016/j.eclinm.2021.100773 (date from preprint), NCT04354428
Dec 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 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
Small early terminated late treatment RCT comparing vitamin C + folic acid, HCQ + folic acid, and HCQ+AZ, showing non-statistically significantly lower hospitalization with HCQ/HCQ+AZ, and faster viral clearance with HCQ. Enrollment was a median of 5.9 days after onset (6.2 and 6.3 in the treatment arms).
The median time to viral clearance for vitamin C + folic acid was 8 days in the preprint but changed to 7 days in the published paper without explanation.
Both vitamin C c19early.org and folic acid Deschasaux-Tanguy, Farag show efficacy in other trials, so the true effectiveness of HCQ(+AZ) may be higher than observed.
Low risk patients, median age 37, no deaths (not matching the title which claims "high risk"). Post hoc addition of a new Ct threshold to obscure the statistically significant faster clearance. No analysis for time from symptom onset. Authors identify (relatively) low and high risk cohorts, but do not provide either viral shedding or symptom resolution results for the cohorts. NCT04354428 (history). For other issues see twitter.com.
risk of hospitalization, 29.9% lower, RR 0.70, p = 0.73, treatment 5 of 148 (3.4%), control 4 of 83 (4.8%), NNT 69, HCQ + folic acid and HCQ + AZ vs. vitamin C + folic acid.
risk of no recovery, 2.0% lower, RR 0.98, p = 0.95, treatment 30 of 60 (50.0%), control 34 of 72 (47.2%), adjusted per study, inverted to make RR<1 favor treatment, HCQ + folic acid vs. vitamin C + folic acid.
risk of no recovery, 9.9% higher, RR 1.10, p = 0.70, treatment 34 of 65 (52.3%), control 34 of 72 (47.2%), adjusted per study, inverted to make RR<1 favor treatment, HCQ + AZ vs. vitamin C + folic acid.
time to viral-, 28.6% lower, relative time 0.71, treatment 49, control 52, median time, HCQ + folic acid vs. vitamin C + folic acid.
time to viral-, 14.3% lower, relative time 0.86, treatment 51, control 52, median time, HCQ + AZ vs. vitamin C + folic acid.
risk of no viral clearance, 38.3% lower, RR 0.62, p = 0.047, treatment 6 of 49 (12.2%), control 12 of 52 (23.1%), NNT 9.2, adjusted per study, inverted to make RR<1 favor treatment, HCQ + folic acid vs. vitamin C + folic acid.
risk of no viral clearance, 20.0% lower, RR 0.80, p = 0.49, treatment 11 of 51 (21.6%), control 12 of 52 (23.1%), adjusted per study, inverted to make RR<1 favor treatment, HCQ + AZ vs. vitamin C + folic acid.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Johnston et al., 9 Dec 2020, Randomized Controlled Trial, USA, peer-reviewed, 30 authors, study period 15 April, 2020 - 27 July, 2020, average treatment delay 5.9 days, dosage 400mg bid day 1, 200mg bid days 2-10, this trial compares with another treatment - results may be better when compared to placebo, trial NCT04354428 (history).
This PaperHCQAll
Hydroxychloroquine with or without azithromycin for treatment of early SARS-CoV-2 infection among high-risk outpatient adults: A randomized clinical trial
Christine Johnston, Elizabeth R Brown, Jenell Stewart, Helen C Stankiewicz Karita, Patricia J Kissinger, John Dwyer, Sybil Hosek, Temitope Oyedele, Michael K Paasche-Orlow, Kristopher Paolino, Kate B Heller, Hannah Leingang, Harald S Haugen, Tracy Q Dong, Anna Bershteyn, Arun R Sridhar, Jeanne Poole, Peter A Noseworthy, Michael J Ackerman, Susan Morrison, Alexander L Greninger, Meei-Li Huang, Keith R Jerome, Mark H Wener, Anna Wald, Joshua T Schiffer, Connie Celum, Helen Y Chu, Ruanne V Barnabas, Jared M Baeten
EClinicalMedicine, doi:10.1016/j.eclinm.2021.100773
Background: Treatment options for outpatients with COVID-19 could reduce morbidity and prevent SARS-CoV-2 transmission. Methods: In this randomized, double-blind, three-arm (1:1:1) placebo-equivalent controlled trial conducted remotely throughout the United States, adult outpatients with laboratory-confirmed SARS-CoV-2 infection were recruited. Participants were randomly assigned to receive hydroxychloroquine (HCQ) (400 mg BID x1day, followed by 200 mg BID x9days) with or without azithromycin (AZ) (500 mg, then 250 mg daily x4days) or placebo-equivalent (ascorbic acid (HCQ) and folic acid (AZ)), stratified by risk for progression to severe COVID-19 (high-risk vs. low-risk). Self-collected nasal swabs for SARS-CoV-2 PCR, FLUPro symptom surveys, EKGs and vital signs were collected daily. Primary endpoints were: (a) 14-day progression to lower respiratory tract infection (LRTI), 28-day COVID-19 related hospitalization, or death; (b) 14-day time to viral clearance; secondary endpoints included time to symptom resolution (ClinicalTrials.gov: NCT04354428). Due to the low rate of clinical outcomes, the study was terminated for operational futility. Findings: Between 15th April and 27th July 2020, 231 participants were enrolled and 219 initiated medication a median of 5.9 days after symptom onset. Among 129 high-risk participants, incident LRTI occurred in six (4.7%) participants (two control, four HCQ/AZ) and COVID-19 related hospitalization in seven (5.4%
Supplementary materials Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.eclinm.2021.100773.
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Late treatment
is less effective
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