Doxycycline is a safe alternative to Hydroxychloroquine + Azithromycin to prevent clinical worsening and hospitalization in mild COVID-19 patients: An open label randomized clinical trial (DOXYCOV)
Objective: We aimed to compare the safety and efficacy of a doxycycline-based regimen against the national standard guidelines (Hydroxychloroquine plus Azithromycin) for the treatment of mild symptomatic COVID-19.
Methods: We conducted an open-label, randomized, non-inferiority trial, in Cameroon comparing Doxycycline 100mg, twice daily for 7 days versus Hydroxychloroquine, 400 mg daily for 5 days and Azithromycin 500mg at day 1 and 250mg from day 2 through 5, in mild COVID-19 patients. Clinical improvement, biological parameters and adverse events were assessed. The primary outcome was the proportion of clinical cure at day 3, 10 and 30. Non-inferiority was determined by the clinical cure rate between protocols with a 20 percentage points margin. Results: 194 participants underwent randomization and were treated with Doxycycline (n=97) or Hydroxychloroquine-Azithromycin (n=97). At day 3, 74/92 (80.4%) participants on Doxycycline versus 77/95 (81.1%) on Hydroxychloroquine-Azithromycin -based protocols were asymptomatic (p=0.91). At day 10, 88/92 (95.7%) participants on Doxycycline versus 93/95 (97.9%) on Hydroxychloroquine-Azithromycin were asymptomatic (p=0.44). At day 30 all participants were asymptomatic. SARS-CoV2 PCR was negative at Day 10 in 60/92 (65.2%) participants allocated to Doxycycline and 63/95 (66.3%) participants allocated to Hydroxychloroquine-Azithromycin. None of the participants were admitted for worsening of the disease after treatment initiation.
Conclusion: Doxycycline 100 mg twice daily for 7 days is as effective and safe as Hydroxychloroquine-Azithromycin, for preventing clinical worsening of mild symptomatic or asymptomatic COVID-19, and achieving virological suppression.
Competing interests The authors declare no competing interests
Ethical approval The study received ethical clearance from the Cameroon National Ethics Committee (N° 2020/07/1585/L/CNERSH/SP). The trial was prospectively registered on ClinicalTrials.gov under number NCT04715295.
Author Contribution Statement Contributors: E-S designed the work, acquired funding, implemented the trial, monitored data collection for the whole trial, monitored statistical analysis, drafted the paper, revised the paper and gave final approval to be published. S-Z designed the work, implemented the trial, monitored data collection, wrote the statistical analysis plan, cleaned and analyzed the data, drafted and revised the paper. M-GF designed the work, revised the draft paper. JC-K designed the work, revised the draft paper. CK member of the data safety monitoring board. LM-K member of the data safety monitoring board. AZ designed the work. YW .
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