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Randomized Controlled Trial
. 2021 May;49(5):3000605211013550.
doi: 10.1177/03000605211013550.

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

Reaz Mahmud  1 , Md Mujibur Rahman  2 , Iftikher Alam  1 , Kazi Gias Uddin Ahmed  1 , A K M Humayon Kabir  2 , S K Jakaria Been Sayeed  2 , Mohammad Aftab Rassel  1 , Farhana Binte Monayem  3 , Md Shahidul Islam  3 , Mohammad Monirul Islam  4 , Anindita Das Barshan  2 , Mohammad Mahfuzul Hoque  2 , Md Uzzal Mallik  2 , Mohammad Abdullah Yusuf  5 , Mohammad Zaid Hossain  2
Affiliations
Randomized Controlled Trial

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

Reaz Mahmud et al. J Int Med Res. 2021 May.

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-to-moderate COVID-19 symptoms randomly assigned to treatment (n = 200) and placebo (n = 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.

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: COVID-19; Ivermectin; doxycycline; infection; recovery time; reverse transcription polymerase chain reaction.

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Conflict of interest statement

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.

Figures

Figure 1.
Figure 1.
Enrollment, randomization, follow up, and analysis of patients according to the CONSORT 2010 flow diagram.
Figure 2.
Figure 2.
Time-to-recovery in the treatment and control groups, with and without censored data. Hazard ratio (95% confidence interval): 0.73 (0.60–0.90); P = 0.003.
Figure 3.
Figure 3.
Post-hoc analysis of time-to-recovery among the subgroups. Data are presented as hazard ratios and 95% confidence intervals.
See this image and copyright information in PMC

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