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Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial

Mahmud et al., Journal of International Medical Research, doi:10.5061/dryad.qjq2bvqf6 (date from preprint), NCT04523831

Oct 2020

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Ivermectin for COVID-19

4th treatment shown to reduce risk in August 2020

^*, now known with p < 0.00000000001 from 102 studies, recognized in 22 countries.

Lower risk for mortality, ventilation, ICU admission, hospitalization, recovery, cases, and viral clearance.

No treatment is 100% effective. Protocols combine complementary and synergistic treatments. ^* >10% efficacy in meta analysis with ≥3 clinical studies.

4,000+ studies for 60+ treatments. c19ivm.org

RCT for ivermectin+doxycycline showing improvements in mortality, recovery, progression, and virological cure. 183 treatment and 183 control patients with no deaths in the treatment arm vs. 3 in the control arm (the 3 control deaths are not included in the analysis of other outcomes). Results may reflect the use of ivermectin, doxycycline, and potential synergistic effects of the combination. In the PRINCIPLE trial, no mortality benefit was seen for doxycycline alone thelancet.com (0.6% mortality with doxycycline vs. 0.2% control).

This is the 6th of 49 COVID-19 RCTs for ivermectin, which collectively show efficacy with p=0.00000038.

This is the 11th of 102 COVID-19 controlled studies for ivermectin, which collectively show efficacy with p<0.0000000001 (1 in 560 quintillion).

1. thelancet.com, www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00310-6/fulltext.www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00310-6/fulltext.

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risk of death, 85.7% lower, HR 0.14, p = 0.25, treatment 0 of 183 (0.0%), control 3 of 183 (1.6%), NNT 61, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).

risk of progression, 57.0% lower, HR 0.43, p < 0.001, treatment 16 of 183 (8.7%), control 32 of 180 (17.8%), NNT 11, adjusted per study, Cox regression.

risk of no recovery, 94.0% lower, HR 0.06, p < 0.001, treatment 72 of 183 (39.3%), control 100 of 180 (55.6%), NNT 6.2, adjusted per study, day 7, Cox regression.

risk of no recovery, 38.5% lower, RR 0.61, p = 0.005, treatment 40 of 183 (21.9%), control 64 of 180 (35.6%), NNT 7.3, day 11.

risk of no recovery, 96.0% lower, HR 0.04, p < 0.001, treatment 42 of 183 (23.0%), control 67 of 180 (37.2%), NNT 7.0, adjusted per study, day 12, Cox regression.

time to recovery, 27.0% lower, HR 0.73, p = 0.003, treatment 183, control 180, Cox regression, primary outcome.

risk of no viral clearance, 39.0% lower, HR 0.61, p = 0.002, treatment 14 of 183 (7.7%), control 36 of 180 (20.0%), NNT 8.1, adjusted per study, Cox regression.

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Mahmud et al., 9 Oct 2020, Double Blind Randomized Controlled Trial, Bangladesh, peer-reviewed, 15 authors, study period 1 June, 2020 - 30 August, 2020, average treatment delay 4.0 days, dosage 12mg single dose, this trial uses multiple treatments in the treatment arm (combined with doxycycline) - results of individual treatments may vary, trial NCT04523831 (history).

This Paper Ivermectin All

Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial

Reaz Mahmud, Md. Mujibur Rahman, Iftikher Alam, Kazi Gias Uddin Ahmed, A K M Humayon Kabir, S K Jakaria Been Sayeed, Mohammad Aftab Rassel, Farhana Binte Monayem, Md Shahidul Islam, Mohammad Monirul Islam, Anindita Das Barshan, Mohammad Mahfuzul Hoque, MD Md. Uzzal Mallik, Mohammad Abdullah Yusuf, Mohammad Zaid Hossain

Journal of International Medical Research, doi:10.1177/03000605211013550

Objective: We evaluated whether ivermectin combined with doxycycline reduced the clinical recovery time in adults with COVID-19 infection. Methods: This was a randomized, blinded, placebo-controlled trial in patients with mild-tomoderate COVID-19 symptoms randomly assigned to treatment (n ¼ 200) and placebo (n ¼ 200) groups. The primary outcome was duration from treatment to clinical recovery. Secondary outcomes were disease progression and persistent COVID-19 positivity by RT-PCR.

Declaration of conflicting interest The authors declare that there is no conflict of interest. Popular Pharmaceuticals Limited, Bangladesh provided ivermectin, doxycycline, and placebo. The company was not involved in the planning or design of the study and had no role in the collection, analysis, or interpretation of the data. Author contributions Appendix

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