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: sagepub.com/journals-permissions DOI: 10.1177/03000605211013550 journals.sagepub.com/home/imr 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: mmrahman61@gmail.com Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) 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 (https://us.sagepub.com/en-us/nam/open-access-at-sage). 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: ClinicalTrials.gov 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