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0 0.5 1 1.5 2+ Mortality 86% Improvement Relative Risk Progression 57% Recovery 94% Recovery (b) 39% Recovery (c) 96% Time to recovery 27% primary Viral clearance 39% Mahmud et al. NCT04523831 Ivermectin RCT EARLY TREATMENT Is early treatment with ivermectin+doxycycline beneficial for COVID-19? Double-blind RCT 366 patients in Bangladesh Lower progression (p=0.001) and improved recovery (p<0.0001) Mahmud et al., J. Int. Medical Research, doi:10.5061/dryad.qjq2bvqf6 Favors ivermectin Favors control
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 earlier preprint), NCT04523831 (history)
Mahmud et al., Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial, Journal of International Medical Research, doi:10.5061/dryad.qjq2bvqf6 (date from earlier preprint), NCT04523831
Oct 2020   Source   PDF  
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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 [] (0.6% mortality with doxycycline vs. 0.2% control).
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.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Mahmud et al., 9 Oct 2020, Double Blind Randomized Controlled Trial, Bangladesh, peer-reviewed, 15 authors, 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).
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Abstract: Clinical Research Report Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial Journal of International Medical Research 49(5) 1–14 ! The Author(s) 2021 Article reuse guidelines: DOI: 10.1177/03000605211013550 Reaz Mahmud1 , Md. Mujibur Rahman2, Iftikher Alam1, Kazi Gias Uddin Ahmed1, A.K.M. Humayon Kabir2, S.K. Jakaria Been Sayeed2, Mohammad Aftab Rassel1, Farhana Binte Monayem3, Md Shahidul Islam3, Mohammad Monirul Islam4, Anindita Das Barshan2, Mohammad Mahfuzul Hoque2, MD. Uzzal Mallik2, Mohammad Abdullah Yusuf5 and Mohammad Zaid Hossain2 Abstract 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. 1 Department of Neurology, Dhaka Medical College, Dhaka, Bangladesh 2 Department of Medicine, Dhaka Medical College Hospital, Dhaka, Bangladesh 3 Sarkari Karmachari Hospital, Dhaka, Bangladesh 4 Ministry of Health Family Welfare, Dhaka, Bangladesh 5 Department of Microbiology, National Institute of Neurosciences and Hospital, Dhaka, Bangladesh Corresponding author: Md. Mujibur Rahman, Department of Medicine, Dhaka Medical College Hospital, Secretariat Road, Shahbagh, Dhaka 1000, Bangladesh. Email: Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( 2 Journal of International Medical Research Results: Among 556 screened patients, 400 were enrolled and 363 completed follow-up. The mean patient age was 40 years, and 59% were men. The median recovery time was 7 (4–10, treatment group) and 9 (5–12, placebo group) days (hazard ratio, 0.73; 95% confidence interval, 0.60–0.90). The number of patients with a 7-day recovery was 61% (treatment group) and 44% (placebo groups) (hazard ratio, 0.06; 95% confidence interval, 0.04–0.09). The proportion of patients who remained RT-PCR positive on day 14 and whose disease did not progress was significantly lower in the treatment group than in the placebo group. Conclusions: Patients with mild-to-moderate COVID-19 infection treated with ivermectin plus doxycycline recovered earlier, were less likely to progress to more serious disease, and were more likely to be COVID-19 negative by RT-PCR on day 14. Trial Registration: Identifier: NCT04523831. Data Repository ID: Dryad. doi:10.5061/dryad.qjq2bvqf6 Keywords Ivermectin, doxycycline, COVID-19, recovery time, infection, reverse transcription polymerase chain reaction Date received: 1 January 2021; accepted: 6 April 2021
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