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.

Strengths and Limitations

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  This study is one of the first randomized trial, assessing the efficacy and tolerance of Doxycycline to treat COVID-19

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  It is one of the first to evaluate disease progression and need to hospitalization in mild or asymptomatic COVID-19

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  Patients will not receive identical treatments

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  Doxycycline has advantages in terms of availability, safety and cost compared to Hydroxychloroquine and Azytromycin

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  Though this study has encounter 7 lost to follow-up, this does not have a major influence on our results

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  These data will assist clinicians in their daily practice, and provide a new tool for the fight against COVID-19